Skip to main content
SpringerLink
Log in

Immunopathology of the Musculoskeletal System

  • Chapter
  • First Online:
Immunopathology in Toxicology and Drug Development

Part of the book series: Molecular and Integrative Toxicology ((MOLECUL))

  • 1260 Accesses

Abstract

The musculoskeletal system is composed chiefly of bone, cartilage, skeletal muscle, tendons, and ligaments, and as such does not serve as a prominent location for immune response elements under normal conditions. However, bone marrow and regional lymph nodes within or near large muscles as well as the existing vascular supply do provide ready access for many immune cell lineages to musculoskeletal components, which may help drive inflammation of these tissues during autoimmune or infectious diseases. Immune-mediated skeletal (bone and joint) diseases are driven by multiple bone-regulatory molecules (including the canonical RANK/RANKL/OPG pathway as well as non-canonical [RANKL-independent] pathways) and also many immune cell-derived pro-inflammatory molecules (especially cytokines and chemokines released by activated lymphocytes, macrophages, and fibroblast-like synoviocytes). Immune-mediated conditions affecting soft tissues (i.e., skeletal muscle and tendons) also are propelled by lymphocyte- and macrophage-derived pro-inflammatory cytokines. Immune system assaults on musculoskeletal tissues often are driven by a loss of self-tolerance to endogenous antigens (i.e., autoimmunity) or to mistaken identity (i.e., molecular mimicry between a pathogen-derived epitope and an endogenous molecule). Improved understanding of immunopathologic diseases affecting the musculoskeletal system has been achieved by evaluating animal models of disease and human patients. The current chapter describes the cellular and molecular components of musculoskeletal immunology and explores common immunopathologic conditions affecting musculoskeletal tissues, including the animal models used to assess potential etiologies, disease mechanisms, and disease-modifying therapies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Ahern BJ, Parvizi J, Boston R, Schaer TP (2009) Preclinical animal models in single site cartilage defect testing: a systematic review. Osteoarthritis Cartilage 17(6):705–713

    Article  CAS  PubMed  Google Scholar 

  • Allenbach Y, Solly S, Grégoire S, Dubourg O, Salomon B, Butler-Browne G, Musset L, Herson S, Klatzmann D, Benveniste O (2009) Role of regulatory T cells in a new mouse model of experimental autoimmune myositis. Am J Pathol 174(3):989–998

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Alunno A, Manetti M, Caterbi S, Ibba-Manneschi L, Bistoni O, Bartoloni E, Valentini V, Terenzi R, Gerli R (2015) Altered immunoregulation in rheumatoid arthritis: the role of regulatory T cells and proinflammatory Th17 cells and therapeutic implications. Mediators Inflamm 2015:751793

    PubMed Central  PubMed  Google Scholar 

  • Ameye LG, Young MF (2006) Animal models of osteoarthritis: lessons learned while seeking the “Holy Grail”. Curr Opin Rheumatol 18(5):537–547

    Article  PubMed  Google Scholar 

  • Arleevskaya MI, Kravtsova OA, Lemerle J, Renaudineau Y, Tsibulkin AP (2016) How rheumatoid arthritis can result from provocation of the immune system by microorganisms and viruses. Front Microbiol 7:1296. doi:10.3389/fmicb.2016.01296

    Article  PubMed Central  PubMed  Google Scholar 

  • Asquith MJ, Stauffer P, Davin S, Mitchell C, Lin P, Rosenbaum JT (2016) Perturbed mucosal immunity and dysbiosis accompany clinical disease in a rat model of spondyloarthritis. Arthritis Rheumatol 68(9):2151–2162

    Article  CAS  PubMed  Google Scholar 

  • Baron R (2008) Anatomy and ultrastructure of bone – histogenesis, growth and remodeling. In: Endotext (www.endotext.org), De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A (eds) MDText.com, Inc., South Dartmouth, MA

  • Bendele AM (2001) Animal models of osteoarthritis. J Musculoskelet Neuronal Interact 1(4):363–376

    Google Scholar 

  • Bendele A, McComb J, Gould T, McAbee T, Sennello G, Chlipala E, Guy M (1999) Animal models of arthritis: relevance to human disease. Toxicol Pathol 27(1):134–142

    Article  CAS  PubMed  Google Scholar 

  • Bengtsson AK, Ryan EJ (2002) Immune function of the decoy receptor osteoprotegerin. Crit Rev Immunol 22(3):201–215

    CAS  PubMed  Google Scholar 

  • Berthelot JM, Sibilia J (2016) Rampant infections of bone marrow stem cell niches as triggers for spondyloarthropathies and rheumatoid arthritis. Clin Exp Rheumatol 34(2):329–336

    PubMed  Google Scholar 

  • Bläss S, Engel JM, Burmester GR (2001) The immunologic homunculus in rheumatoid arthritis. A new viewpoint of immunopathogenesis in rheumatoid arthritis and therapeutic consequences [German]. Z Rheumatol 60(1):1–16

    Article  PubMed  Google Scholar 

  • Block KE, Zheng Z, Dent AL, Kee BL, Huang H (2016) Gut microbiota regulates K/BxN autoimmune arthritis through follicular helper T but not Th17 cells. J Immunol 196(4):1550–1557

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bolon B (2012) Cellular and molecular mechanisms of autoimmune disease. Toxicol Pathol 40(2):216–229

    Article  CAS  PubMed  Google Scholar 

  • Bolon B, Grisanti M, Villasenor K, Morony S, Feige U, Simonet WS (2015) Generalized degenerative joint disease in osteoprotegerin (Opg) null mutant mice. Vet Pathol 52(5):873–882

    Article  CAS  PubMed  Google Scholar 

  • Bolon B, Shalhoub V, Kostenuik PJ, Campagnuolo G, Morony S, Boyle WJ, Zack D, Feige U (2002) Osteoprotegerin (OPG): an endogenous anti-osteoclast factor for protecting bone in rheumatoid arthritis. Arthritis Rheum 46(12):3121–3135

    Article  CAS  PubMed  Google Scholar 

  • Bolon B, Stolina M, King C, Middleton S, Gasser J, Zack D, Feige U (2011) Rodent preclinical models for developing novel antiarthritic molecules: comparative biology and preferred methods for evaluating efficacy. J Biomed Biotechnol 2011:569068

    Article  PubMed  Google Scholar 

  • Boyle WJ, Simonet WS, Lacey DL (2003) Osteoclast differentiation and activation. Nature 423(6937):337–342

    Article  CAS  PubMed  Google Scholar 

  • Brändström H, Jonsson KB, Vidal O, Ljunghall S, Ohlsson C, Ljunggren Ö (1998) Tumor necrosis factor-α and -β upregulate the levels of osteoprotegerin mRNA in human osteosarcoma MG-63 cells. Biochem Biophys Res Commun 248(3):454–457

    Article  PubMed  Google Scholar 

  • Braun T, Zwerina J (2011) Positive regulators of osteoclastogenesis and bone resorption in rheumatoid arthritis. Arthritis Res Ther 13(4):235

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bugatti S, Manzo A, Caporali R, Montecucco C (2012) Inflammatory lesions in the bone marrow of rheumatoid arthritis patients: a morphological perspective. Arthritis Res Ther 14(6):229

    Article  PubMed Central  PubMed  Google Scholar 

  • Bugatti S, Vitolo B, Caporali R, Montecucco C, Manzo A (2014) B cells in rheumatoid arthritis: from pathogenic players to disease biomarkers. BioMed Res Int 2014:681678

    Article  PubMed Central  PubMed  Google Scholar 

  • Burmester GR, Feist E, Dorner T (2014) Emerging cell and cytokine targets in rheumatoid arthritis. Nat Rev Rheumatol 10(2):77–88

    Article  CAS  PubMed  Google Scholar 

  • Caetano-Lopes J, Canhao H, Fonseca JE (2009) Osteoimmunology – the hidden immune regulation of bone. Autoimmun Rev 8(3):250–255

    Article  CAS  PubMed  Google Scholar 

  • Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, Martin RP, Schipani E, Divieti P, Bringhurst FR, Milner LA, Kronenberg HM, Scadden DT (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425(6960):841–846

    Article  CAS  PubMed  Google Scholar 

  • Campagnuolo G, Bolon B, Feige U (2002) Kinetics of bone protection by recombinant osteoprotegerin therapy in Lewis rats with adjuvant arthritis. Arthritis Rheum 46(7):1926–1936

    Article  CAS  PubMed  Google Scholar 

  • Carrasco S, Neves FS, Fonseca MH, Goncalves CR, Saad CG, Sampaio-Barros PD, Goldenstein-Schainberg C (2011) Toll-like receptor (TLR) 2 is upregulated on peripheral blood monocytes of patients with psoriatic arthritis: a role for a gram-positive inflammatory trigger? Clin Exp Rheumatol 29(6):958–962

    PubMed  Google Scholar 

  • Chappert P (2014) Role of SFB [segmented filamentous bacteria] in autoimmune arthritis: an example of regulation of autoreactive T cell sensitivity in the gut. Gut Microbes 5(2):259–264

    Article  PubMed Central  PubMed  Google Scholar 

  • Chen M, Guo Z, Ju W, Ryffel B, He X, Zheng SG (2012) The development and function of follicular helper T cells in immune responses. Cell Mol Immunol 9(5):375–379

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cheng ML, Fong L (2014) Effects of RANKL-targeted therapy in immunity and cancer. Front Oncol 3:329

    Article  PubMed Central  PubMed  Google Scholar 

  • Choi Y, Arron JR, Townsend MJ (2009) Promising bone-related therapeutic targets for rheumatoid arthritis. Nat Rev Rheumatol 5(10):543–548

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cook JL, Kuroki K, Visco D, Pelletier JP, Schulz L, Lafeber FP (2010) The OARSI histopathology initiative–recommendations for histological assessments of osteoarthritis in the dog. Osteoarthritis Cartilage 18(3):S66–S79

    Google Scholar 

  • Cooles FA, Isaacs JD, Anderson AE (2013) Treg cells in rheumatoid arthritis: an update. Curr Rheumatol Rep 15(9):352

    Article  PubMed  CAS  Google Scholar 

  • Costamagna D, Costelli P, Sampaolesi M, Penna F (2015) Role of inflammation in muscle homeostasis and myogenesis. Mediators Inflamm 2015:805172

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Crotti TN, Smith MD, Weedon H, Ahern MJ, Findlay DM, Kraan M, Tak PP, Haynes DR (2002) Receptor activator NF-κB ligand (RANKL) expression in synovial tissue from patients with rheumatoid arthritis, spondyloarthropathy, osteoarthritis, and from normal patients: semiquantitative and quantitative analysis. Ann Rheum Dis 61(12):1047–1054

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Culley KL, Dragomir CL, Chang J, Wondimu EB, Coico J, Plumb DA, Otero M, Goldring MB (2015) Mouse models of osteoarthritis: surgical model of posttraumatic osteoarthritis induced by destabilization of the medial meniscus. Methods Mol Biol 1226:143–173

    Article  CAS  PubMed  Google Scholar 

  • Dai SM, Nishioka K, Yudoh K (2004) Interleukin (IL) 18 stimulates osteoclast formation through synovial T cells in rheumatoid arthritis: comparison with IL1β and tumour necrosis factor α. Ann Rheum Dis 63(11):1379–1386

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Danks L, Komatsu N, Guerrini MM, Sawa S, Armaka M, Kollias G, Nakashima T, Takayanagi H (2016) RANKL expressed on synovial fibroblasts is primarily responsible for bone erosions during joint inflammation. Ann Rheum Dis 75(6):1187–1195

    Article  CAS  PubMed  Google Scholar 

  • Danks L, Takayanagi H (2013) Immunology and bone. J Biochem 154(1):29–39

    Article  CAS  PubMed  Google Scholar 

  • David JP (2007) Osteoimmunology: a view from the bone. Adv Immunol 95:149–165

    Article  CAS  PubMed  Google Scholar 

  • de Lange-Brokaar BJ, Ioan-Facsinay A, van Osch GJ, Zuurmond AM, Schoones J, Toes RE, Huizinga TW, Kloppenburg M (2012) Synovial inflammation, immune cells and their cytokines in osteoarthritis: a review. Osteoarthritis Cartilage 20(12):1484–1499

    Article  PubMed  Google Scholar 

  • De Paepe B, Zschüntzsch J (2015) Scanning for therapeutic targets within the cytokine network of idiopathic inflammatory myopathies. Int J Mol Sci 16(8):18683–18713

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Dietert RR, DeWitt JC, Luebke RW (2012) Reducing the prevalence of immune-based chronic disease. In: Dietert RR, Luebke RW (eds) Immunotoxicity, immune dysfunction, and chronic disease. Molecular and integrative toxicology. Springer, New York, pp 419–440

    Chapter  Google Scholar 

  • Dong C, Flavell RA (2000) Cell fate decision: T-helper 1 and 2 subsets in immune responses. Arthritis Res 2(3):179–188

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dorożyńska I, Majewska-Szczepanik M, Marcińska K, Szczepanik M (2014) Partial depletion of natural gut flora by antibiotic aggravates collagen induced arthritis (CIA) in mice. Pharmacol Rep 66(2):250–255

    Article  PubMed  CAS  Google Scholar 

  • Dougall WC, Glaccum M, Charrier K, Rohrbach K, Brasel K, De Smedt T, Daro E, Smith J, Tometsko ME, Maliszewski CR, Armstrong A, Shen V, Bain S, Cosman D, Anderson D, Morrissey PJ, Peschon JJ, Schuh J (1999) RANK is essential for osteoclast and lymph node development. Genes Dev 13(18):2412–2424

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Dwivedi N, Radic M (2014) Citrullination of autoantigens implicates NETosis in the induction of autoimmunity. Ann Rheum Dis 73(3):483–491

    Article  CAS  PubMed  Google Scholar 

  • Feige U, Hu Y-L, Gasser J, Campagnuolo G, Munyakazi L, Bolon B (2000) Anti-interleukin-1 and anti-tumor necrosis factor-α synergistically inhibit adjuvant arthritis in Lewis rats. Cell Mol Life Sci 57(10):1457–1470

    Article  CAS  PubMed  Google Scholar 

  • Ferguson PJ, Bing X, Vasef MA, Ochoa LA, Mahgoub A, Waldschmidt TJ, Tygrett LT, Schlueter AJ, El-Shanti H (2006) A missense mutation in pstpip2 is associated with the murine autoinflammatory disorder chronic multifocal osteomyelitis. Bone 38(1):41–47

    Article  CAS  PubMed  Google Scholar 

  • Forbes JD, Van Domselaar G, Bernstein CN (2016) The gut microbiota in immune-mediated inflammatory diseases. Front Microbiol 7:1081

    Article  PubMed Central  PubMed  Google Scholar 

  • Fox JG, Barthold SW, Davisson MT, Newcomer CE, Quimby FW, Smith AL (2007) The Mouse in Biomedical Research: Vol 4. Immunology, 2nd edn. Academic, San Diego

    Google Scholar 

  • Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 69(Suppl 1):S4–S9

    Article  PubMed  Google Scholar 

  • Gaston JS (2008) Cytokines in arthritis—the 'big numbers' move centre stage. Rheumatology (Oxford) 47(1):8–12

    Article  CAS  Google Scholar 

  • Gerwin N, Bendele AM, Glasson S, Carlson CS (2010) The OARSI histopathology initiative - recommendations for histological assessments of osteoarthritis in the rat. Osteoarthritis Cartilage 18(Suppl 3):S24–S34

    Article  PubMed  Google Scholar 

  • Gherardi RK (2011) Pathogenic aspects of dermatomyositis, polymyositis and overlap myositis. Presse Med 40(4 Pt 2):e209–e218

    Article  PubMed  Google Scholar 

  • Glasson SS (2007) In vivo osteoarthritis target validation utilizing genetically-modified mice. Curr Drug Targets 8(2):367–376

    Article  CAS  PubMed  Google Scholar 

  • Glasson SS, Chambers MG, Van Den Berg WB, Little CB (2010) The OARSI histopathology initiative – recommendations for histological assessments of osteoarthritis in the mouse. Osteoarthritis Cartilage 18(3):S17–S23

    Google Scholar 

  • Godessart N, Kunkel SL (2001) Chemokines in autoimmune disease. Curr Opin Immunol 13(6):670–675

    Article  CAS  PubMed  Google Scholar 

  • Goldring MB (1999) The role of cytokines as inflammatory mediators in osteoarthritis: lessons from animal models. Connect Tissue Res 40(1):1–11

    Article  CAS  PubMed  Google Scholar 

  • Greene MA, Loeser RF (2015) Aging-related inflammation in osteoarthritis. Osteoarthritis Cartilage 23(11):1966–1971

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gross DM, Huber BT (2000) Cellular and molecular aspects of Lyme arthritis. Cell Mol Life Sci 57(11):1562–1569

    Article  CAS  PubMed  Google Scholar 

  • Grosse J, Chitu V, Marquardt A, Hanke P, Schmittwolf C, Zeitlmann L, Schropp P, Barth B, Yu P, Paffenholz R, Stumm G, Nehls M, Stanley ER (2006) Mutation of mouse Mayp/Pstpip2 causes a macrophage autoinflammatory disease. Blood 107(8):3350–3358

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Guerrini MM, Takayanagi H (2014) The immune system, bone and RANKL. Arch Biochem Biophys 561:118–123

    Article  CAS  PubMed  Google Scholar 

  • Haynes DR, Crotti TN, Loric M, Bain GI, Atkins GJ, Findlay DM (2001) Osteoprotegerin and receptor activator of nuclear factor κB ligand (RANKL) regulate osteoclast formation by cells in the human rheumatoid arthritic joint. Rheumatology 40(6):623–630

    Article  CAS  PubMed  Google Scholar 

  • Hegen M, Keith JCJ, Collins M, Nickerson-Nutter CL (2008) Utility of animal models for identification of potential therapeutics for rheumatoid arthritis. Ann Rheum Dis 67(11):1505–1515

    Article  CAS  PubMed  Google Scholar 

  • Hodge JM, Collier FM, Pavlos NJ, Kirkland MA, Nicholson GC (2011) M-CSF potently augments RANKL-induced resorption activation in mature human osteoclasts. PLoS One 6(6):e21462

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hofbauer LC, Dunstan CR, Spelsberg TC, Riggs BL, Khosla S (1998) Osteoprotegerin production by human osteoblast lineage cells is stimulated by vitamin D, bone morphogenetic protein-2, and cytokines. Biochem Biophys Res Commun 250(3):776–781

    Article  CAS  PubMed  Google Scholar 

  • Hofbauer LC, Gori F, Riggs BL, Lacey DL, Dunstan CR, Spelsberg TC, Khosla S (1999a) Stimulation of osteoprotegerin ligand and inhibition of osteoprotegerin production by glucocorticoids in human osteoblastic lineage cells: potential paracrine mechanisms of glucocorticoid-induced osteoporosis. Endocrinology 140(10):4382–4389

    CAS  Google Scholar 

  • Hofbauer LC, Hicok KC, Chen D, Khosla S (2002) Regulation of osteoprotegerin production by androgens and anti-androgens in human osteoblastic lineage cells. Eur J Endocrinol 147(2):269–273

    Article  CAS  PubMed  Google Scholar 

  • Hofbauer LC, Khosla S, Dunstan CR, Lacey DL, Spelsberg TC, Riggs BL (1999b) Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology 140(9):4367–4370

    CAS  PubMed  Google Scholar 

  • Hofbauer LC, Lacey DL, Dunstan CR, Spelsberg TC, Riggs BL, Khosla S (1999c) Interleukin-1β and tumor necrosis factor-α, but not interleukin-6, stimulate osteoprotegerin ligand gene expression in human osteoblastic cells. Bone 25(3):255–259

    Article  CAS  PubMed  Google Scholar 

  • Hofbauer LC, Shui C, Riggs BL, Dunstan CR, Spelsberg TC, O'Brien T, Khosla S (2001) Effects of immunosuppressants on receptor activator of NF-κB ligand and osteoprotegerin production by human osteoblastic and coronary artery smooth muscle cells. Biochem Biophys Res Commun 280(1):334–339

    Article  CAS  PubMed  Google Scholar 

  • Hofmann SR, Roesen-Wolff A, Hahn G, Hedrich CM (2012) Update: cytokine dysregulation in chronic nonbacterial osteomyelitis (CNO). Int J Rheumatol 2012:310206

    Article  PubMed Central  PubMed  Google Scholar 

  • Hootman JM, Helmick CG (2006) Projections of US prevalence of arthritis and associated activity limitations. Arthritis Rheum 54(1):226–229

    Article  PubMed  Google Scholar 

  • Horwood NJ, Elliott J, Martin TJ, Gillespie MT (1998) Osteotropic agents regulate the expression of osteoclast differentiation factor and osteoprotegerin in osteoblastic stromal cells. Endocrinology 139(11):4743–4746

    Article  CAS  PubMed  Google Scholar 

  • Houard X, Goldring MB, Berenbaum F (2013) Homeostatic mechanisms in articular cartilage and role of inflammation in osteoarthritis. Curr Rheumatol Rep 15(11):375

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Hsu YH, Chang MS (2010) Interleukin-20 antibody is a potential therapeutic agent for experimental arthritis. Arthritis Rheum 62(11):3311–3321

    Article  CAS  PubMed  Google Scholar 

  • Huebner JL, Hanes MA, Beekman B, TeKoppele JM, Kraus VB (2002) A comparative analysis of bone and cartilage metabolism in two strains of guinea-pig with varying degrees of naturally occurring osteoarthritis. Osteoarthritis Cartilage 10(10):758–767

    Article  CAS  PubMed  Google Scholar 

  • Ishida N, Hayashi K, Hoshijima M, Ogawa T, Koga S, Miyatake Y, Kumegawa M, Kimura T, Takeya T (2002) Large scale gene expression analysis of osteoclastogenesis in vitro and elucidation of NFAT2 as a key regulator. J Biol Chem 277(3):41147–41156

    Article  CAS  PubMed  Google Scholar 

  • Ishiguro N, Ito T, Ito H, Iwata H, Jugessur H, Ionescu M, Poole AR (1999) Relationship of matrix metalloproteinases and their inhibitors to cartilage proteoglycan and collagen turnover: analyses of synovial fluid from patients with osteoarthritis. Arthritis Rheum 42:129–136

    Article  CAS  PubMed  Google Scholar 

  • Jansson A, Renner ED, Ramser J, Mayer A, Haban M, Meindl A, Grote V, Diebold J, Jansson V, Schneider K, Belohradsky BH (2007) Classification of non-bacterial osteitis: retrospective study of clinical, immunological and genetic aspects in 89 patients. Rheumatology (Oxford) 46(1):154–160

    Article  CAS  Google Scholar 

  • Jiao K, Niu LN, Li QH, Ren GT, Zhao CM, Liu YD, Tay FR, Wang MQ (2015) β2-Adrenergic signal transduction plays a detrimental role in subchondral bone loss of temporomandibular joint in osteoarthritis. Sci Rep 5:12593

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Jimi E, Nakamura I, Amano H, Taguchi Y, Tsurukai T, Tamura M, Takahashi N, Suda T (1996) Osteoclast function is activated by osteoblastic cells through a mechanism involving cell-to-cell contact. Endocrinology 137(8):2187–2190

    Article  CAS  Google Scholar 

  • Kaneko T, Mii A, Fukui M, Nagahama K, Shimizu A, Tsuruoka S (2015) IgA nephropathy and psoriatic arthritis that improved with steroid pulse therapy and mizoribine in combination with treatment for chronic tonsillitis and epipharyngitis. Intern Med 54(9):1085–1090

    Article  PubMed  Google Scholar 

  • Kang J, Zhang HY, Feng GD, Feng DY, Jia HG (2015) Development of an improved animal model of experimental autoimmune myositis. Int J Clin Exp Pathol 8(11):14457–14464

    PubMed Central  PubMed  Google Scholar 

  • Keyszer GM, Heer AH, Gay S (1994) Cytokines and oncogenes in cellular interactions of rheumatoid arthritis. Stem Cells 12(1):75–86

    Article  CAS  PubMed  Google Scholar 

  • Kim JH, Kim N (2016) Signaling pathways in osteoclast differentiation. Chonnam Med J 52(1):12–17

    Article  PubMed Central  PubMed  Google Scholar 

  • Kim KW, Kim HR, Park JY, Park JS, Oh HJ, Woo YJ, Park MK, Cho ML, Lee SH (2012) Interleukin-22 promotes osteoclastogenesis in rheumatoid arthritis through induction of RANKL in human synovial fibroblasts. Arthritis Rheum 64(4):1015–1023

    Article  CAS  PubMed  Google Scholar 

  • Klippel JH, Stone JH, Crofford LJ, White PH (2008) Primer on the rheumatic diseases, 13th edn. Arthritis Foundation, Atlanta, GA

    Book  Google Scholar 

  • Kode A, Manavalan JS, Mosialou I, Bhagat G, Rathinam CV, Luo N, Khiabanian H, Lee A, Murty VV, Friedman R, Brum A, Park D, Galili N, Mukherjee S, Teruya-Feldstein J, Raza A, Rabadan R, Berman E, Kousteni S (2014) Leukaemogenesis induced by an activating β-catenin mutation in osteoblasts. Nature 506(7487):240–244

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kohyama K, Matsumoto Y (1999) C-protein in the skeletal muscle induces severe autoimmune polymyositis in Lewis rats. J Neuroimmunol 98(2):130–135

    Article  CAS  PubMed  Google Scholar 

  • Koller MD (2006) Targeted therapy in rheumatoid arthritis. Wien Med Wochenschr 156(1-2):53–60

    Article  PubMed  Google Scholar 

  • Komatsu N, Takayanagi H (2015) Regulatory T cells in arthritis. Prog Mol Biol Transl Sci 136:207–215

    Article  CAS  PubMed  Google Scholar 

  • Kong YY, Boyle WJ, Penninger JM (2000) Osteoprotegerin ligand: a regulator of immune response and bone physiology. Immunol Today 21(10):495–502

    Article  CAS  PubMed  Google Scholar 

  • Kong YY, Feige U, Sarosi I, Bolon B, Tafuri A, Morony S, Capparelli C, Li J, Elliott R, McCabe S, Wong T, Campagnuolo G, Moran E, Bogoch ER, Van G, Nguyen LT, Ohashi PS, Lacey DL, Fish E, Boyle WJ, Penninger JM (1999) Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature 402(6759):304–309

    Article  CAS  PubMed  Google Scholar 

  • Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, Saito S, Inoue K, Kamatani N, Gillespie MT, Martin TJ, Suda T (1999) IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest 103(9):1345–1352

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kraus VB, Huebner JL, DeGroot J, Bendele A (2010) The OARSI histopathology initiative–recommendations for histological assessments of osteoarthritis in the guinea pig. Osteoarthritis Cartilage 18(3):S35–S52

    Google Scholar 

  • Kuca-Warnawin EH, Kurowska WJ, Radzikowska A, Massalska MA, Burakowski T, Kontny E, Slowinska I, Gasik R, Maslinski W (2016) Different expression of chemokines in rheumatoid arthritis and osteoarthritis bone marrow. Reumatologia 54(2):51–53

    Article  PubMed Central  PubMed  Google Scholar 

  • Kulmatycki KM, Jamali F (2005) Drug disease interactions: role of inflammatory mediators in disease and variability in drug response. J Pharm Pharm Sci 8(3):602–625

    CAS  PubMed  Google Scholar 

  • Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ (1998) Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell 93(2):165–176

    Article  CAS  PubMed  Google Scholar 

  • Laverty S, Girard CA, Williams JM, Hunziker EB, Pritzker KP (2010) The OARSI histopathology initiative – recommendations for histological assessments of osteoarthritis in the rabbit. Osteoarthritis Cartilage 18(3):S53–S65

    Google Scholar 

  • Lerner UH (1994) Regulation of bone metabolism by the kallikrein-kinin system, the coagulation cascade, and the acute-phase reactants. Oral Surg Oral Med Oral Pathol 78(4):481–493

    Article  CAS  PubMed  Google Scholar 

  • Lerner UH, Persson E (2008) Osteotropic effects by the neuropeptides calcitonin gene-related peptide, substance P and vasoactive intestinal peptide. J Musculoskelet Neuronal Interact 8(2):154–165

    CAS  PubMed  Google Scholar 

  • Levesque JP, Helwani FM, Winkler IG (2010) The endosteal ‘osteoblastic’ niche and its role in hematopoietic stem cell homing and mobilization. Leukemia 24(12):1979–1992

    Article  PubMed  Google Scholar 

  • Levine YA, Koopman FA, Faltys M, Caravaca A, Bendele A, Zitnik R, Vervoordeldonk MJ, Tak PP (2014) Neurostimulation of the cholinergic anti-inflammatory pathway ameliorates disease in rat collagen-induced arthritis. PLoS One 9(8):e104530

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Li J, Hsu HC, Mountz JD (2012) Managing macrophages in rheumatoid arthritis by reform or removal. Curr Rheumatol Rep 14(5):445–454

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Li S, Zou D, Li C, Meng H, Sui W, Feng S, Cheng T, Zhai Q, Qiu L (2015) Targeting stem cell niche can protect hematopoietic stem cells from chemotherapy and G-CSF treatment. Stem Cell Res Ther 6:175

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Little CB, Smith MM, Cake MA, Read RA, Murphy MJ, Barry FP (2010) The OARSI histopathology initiative – recommendations for histological assessments of osteoarthritis in sheep and goats. Osteoarthritis Cartilage 18(3):S80–S92

    Google Scholar 

  • Little CB, Zaki S (2012) What constitutes an “animal model of osteoarthritis”—the need for consensus? Osteoarthritis Cartilage 20(4):261–267

    Article  CAS  PubMed  Google Scholar 

  • Lomaga MA, Yeh WC, Sarosi I, Duncan GS, Furlonger C, Ho A, Morony S, Capparelli C, Van G, Kaufman S, van der Heiden A, Itie A, Wakeham A, Khoo W, Sasaki T, Cao ZD, Penninger JM, Paige CJ, Lacey DL, Dunstan CR, Boyle WJ, Goeddel DV, Mak TW (1999) TRAF6 deficiency results in osteopetrosis and defective interleukin-1, CD40, and LPS signaling. Genes Dev 13(8):1015–1024

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lowin T, Straub RH (2015) Synovial fibroblasts integrate inflammatory and neuroendocrine stimuli to drive rheumatoid arthritis. Expert Rev Clin Immunol 11(10):1069–1071

    Article  CAS  PubMed  Google Scholar 

  • Malemud CJ (2015) Biologic basis of osteoarthritis: state of the evidence. Curr Opin Rheumatol 27(3):289–294

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Malik A, Hayat G, Kalia JS, Guzman MA (2016) Idiopathic inflammatory myopathies: clinical approach and management. Front Neurol 7:64

    Article  PubMed Central  PubMed  Google Scholar 

  • Marzaioli V, McMorrow JP, Angerer H, Gilmore A, Crean D, Zocco D, Rooney P, Veale D, Fearon U, Gogarty M, McEvoy AN, Stradner MH, Murphy EP (2012) Histamine contributes to increased RANKL to osteoprotegerin ratio through altered nuclear receptor 4A activity in human chondrocytes. Arthritis Rheum 64(10):3290–3301

    Article  CAS  PubMed  Google Scholar 

  • Mateen S, Zafar A, Moin S, Khan AQ, Zubair S (2016) Understanding the role of cytokines in the pathogenesis of rheumatoid arthritis. Clin Chim Acta 455:161–171

    Article  CAS  PubMed  Google Scholar 

  • Matsubara S, Okumura S (1996) Experimental autoimmune myositis in SJL/J mice produced by immunization with syngeneic myosin B fraction. Transfer by both immunoglobulin G and T cells. J Neurol Sci 144(1-2):171–175

    Article  CAS  PubMed  Google Scholar 

  • Matsubara S, Takamori M (1987) Experimental allergic myositis: strain 13 guinea pig immunised with rabbit myosin B fraction. Acta Neuropathol 74(2):158–162

    Article  CAS  PubMed  Google Scholar 

  • McCoy AM (2015) Animal models of osteoarthritis: comparisons and key considerations. Vet Pathol 52(5):803–818

    Article  CAS  PubMed  Google Scholar 

  • McIlwraith CW, Frisbie DD, Kawcak CE, Fuller CJ, Hurtig M, Cruz A (2010). The OARSI histopathology initiative – recommendations for histological assessments of osteoarthritis in the horse. Osteoarthritis Cartilage 18(3):S93–105

    Google Scholar 

  • McInnes IB, Schett G (2011) The pathogenesis of rheumatoid arthritis. N Engl J Med 365(23):2205–2219

    Article  CAS  PubMed  Google Scholar 

  • Ménard HA, Lapointe E, Rochdi MD, Zhou ZJ (2000) Insights into rheumatoid arthritis derived from the Sa immune system. Arthritis Res 2(6):429–432

    Article  PubMed Central  PubMed  Google Scholar 

  • Miyamoto K, Yoshida S, Kawasumi M, Hashimoto K, Kimura T, Sato Y, Kobayashi T, Miyauchi Y, Hoshi H, Iwasaki R, Miyamoto H, Hao W, Morioka H, Chiba K, Kobayashi T, Yasuda H, Penninger JM, Toyama Y, Suda T, Miyamoto T (2011) Osteoclasts are dispensable for hematopoietic stem cell maintenance and mobilization. J Exp Med 208(11):2175–2181

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Mizuno A, Amizuka N, Irie K, Murakami A, Fujise N, Kanno T, Sato Y, Nakagawa N, Yasuda H, Mochizuki S, Gomibuchi T, Yano K, Shima N, Washida N, Tsuda E, Morinaga T, Higashio K, Ozawa H (1998) Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor/osteoprotegerin. Biochem Biophys Res Commun 247(3):610–615

    Article  CAS  PubMed  Google Scholar 

  • Murakami T, Yamamoto M, Ono K, Nishikawa M, Nagata N, Motoyoshi K, Akatsu T (1998) Transforming growth factor-β1 increases mRNA levels of osteoclastogenesis inhibitory factor in osteoblastic/stromal cells and inhibits the survival of murine osteoclast-like cells. Biochem Biophys Res Commun 252(3):747–752

    Article  CAS  PubMed  Google Scholar 

  • Muth IE, Zschüntzsch J, Kleinschnitz K, Wrede A, Gerhardt E, Balcarek P, Schreiber-Katz O, Zierz S, Dalakas MC, Voll RE, Schmidt J (2015) HMGB1 and RAGE in skeletal muscle inflammation: implications for protein accumulation in inclusion body myositis. Exp Neurol 271:189–197

    Article  CAS  PubMed  Google Scholar 

  • Muto M, Date Y, Ichimiya M, Moriwaki Y, Mori K, Kamikawaji N, Kimura A, Sasazuki T, Asagami C (1996) Significance of antibodies to streptococcal M protein in psoriatic arthritis and their association with HLA-A*0207. Tissue Antigens 48(6):645–650

    Article  CAS  PubMed  Google Scholar 

  • Myers LK, Rosloniec EF, Cremer MA, Kang AH (1997) Collagen-induced arthritis, an animal model of autoimmunity. Life Sci 61(19):1861–1878

    Article  CAS  PubMed  Google Scholar 

  • Nagai M, Sato N (1999) Reciprocal gene expression of osteoclastogenesis inhibitory factor and osteoclast differentiation factor regulates osteoclast formation. Biochem Biophys Res Commun 257(3):719–723

    Article  CAS  PubMed  Google Scholar 

  • Nagaraju K, Raben N, Merritt G, Loeffler L, Kirk K, Plotz P (1998) A variety of cytokines and immunologically relevant surface molecules are expressed by normal human skeletal muscle cells under proinflammatory stimuli. Clin Exp Immunol 113(3):407–414

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Negishi-Koga T, Takayanagi H (2009) Ca2+-NFATc1 signaling is an essential axis of osteoclast differentiation. Immunol Rev 231(1):241–256

    Article  CAS  PubMed  Google Scholar 

  • Nikkari S, Merilahti-Palo R, Saario R, Soderstrom KO, Granfors K, Skurnik M, Toivanen P (1992) Yersinia-triggered reactive arthritis. Use of polymerase chain reaction and immunocytochemical staining in the detection of bacterial components from synovial specimens. Arthritis Rheum 35(6):682–687

    Google Scholar 

  • Okamoto K, Takayanagi H (2011) Regulation of bone by the adaptive immune system in arthritis. Arthritis Res Ther 13(3):219

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ponnappan S, Ponnappan U (2011) Aging and immune function: molecular mechanisms to interventions. Antioxid Redox Signal 14(8):1551–1585

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Punzi L, Betterle C (2004) Chronic autoimmune thyroiditis and rheumatic manifestations. Joint Bone Spine 71(4):275–283

    Google Scholar 

  • Raïch-Regué D, Glancy M, Thomson AW (2014) Regulatory dendritic cell therapy: from rodents to clinical application. Immunol Lett 161(2):216–221

    Article  PubMed  CAS  Google Scholar 

  • Rantakokko K, Rimpilainen M, Uksila J, Jansen C, Luukkainen R, Toivanen P (1997) Antibodies to streptococcal cell wall in psoriatic arthritis and cutaneous psoriasis. Clin Exp Rheumatol 15(4):399–404

    CAS  PubMed  Google Scholar 

  • Rayavarapu S, Coley W, Kinder TB, Nagaraju K (2013) Idiopathic inflammatory myopathies: pathogenic mechanisms of muscle weakness. Skelet Muscle 3(1):13

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sabokbar A, Mahoney DJ, Hemingway F, Athanasou NA (2016) Non-canonical (RANKL-independent) pathways of osteoclast differentiation and their role in musculoskeletal diseases. Clin Rev Allergy Immunol 51(1):16–26

    Article  CAS  PubMed  Google Scholar 

  • Sato K, Suematsu A, Okamoto K, Yamaguchi A, Morishita Y, Kadono Y, Tanaka S, Kodama T, Akira S, Iwakura Y, Cua DJ, Takayanagi H (2006) Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction. J Exp Med 203(12):2673–2682

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Sato K, Takayanagi H (2006) Osteoclasts, rheumatoid arthritis, and osteoimmunology. Curr Opin Rheumatol 18(4):419–426

    Article  CAS  PubMed  Google Scholar 

  • Schinnerling K, Soto L, Garcia-González P, Catalán D, Aguillón JC (2015) Skewing dendritic cell differentiation towards a tolerogenic state for recovery of tolerance in rheumatoid arthritis. Autoimmun Rev 14(6):517–527

    Article  CAS  PubMed  Google Scholar 

  • Sigurdardottir SL, Thorleifsdottir RH, Valdimarsson H, Johnston A (2013) The association of sore throat and psoriasis might be explained by histologically distinctive tonsils and increased expression of skin-homing molecules by tonsil T cells. Clin Exp Immunol 174(1):139–151

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Silverstein AM, Stoker AM, Ateshian GA, Bulinski JC, Cook JL, Hung CT (2016) Transient expression of the diseased phenotype of osteoarthritic chondrocytes in engineered cartilage. J Orthop Res. doi:10.1002/jor.23301. In press

  • Simon JP, Marie I, Jouen F, Boyer O, Martinet J (2016) Autoimmune myopathies: where do we stand? Front Immunol 7:234

    Article  PubMed Central  PubMed  Google Scholar 

  • Smith DA, Germolec DR (1999) Introduction to immunology and autoimmunity. Environ Health Perspect 107(Suppl 5):661–665

    Article  PubMed Central  PubMed  Google Scholar 

  • Song J, Kiel MJ, Wang Z, Wang J, Taichman RS, Morrison SJ, Krebsbach PH (2010) An in vivo model to study and manipulate the hematopoietic stem cell niche. Blood 115(13):2592–2600

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Stolina M, Bolon B, Dwyer D, Middleton S, Duryea D, Kostenuik PJ, Feige U, Zack DJ (2008) The evolving systemic and local biomarker milieu at different stages of disease progression in rat collagen-induced arthritis. Biomarkers 13(7):692–712

    Article  CAS  PubMed  Google Scholar 

  • Stolina M, Bolon B, Middleton S, Dwyer D, Brown H, Duryea D, Zhu L, Rohner A, Pretorius J, Kostenuik P, Feige U, Zack D (2009) The evolving systemic and local biomarker milieu at different stages of disease progression in rat adjuvant-induced arthritis. J Clin Immunol 29(2):158–174

    Article  CAS  PubMed  Google Scholar 

  • Suda T, Takahashi N, Udagawa N, Jimi E, Gillespie MT, Martin TJ (1999) Modulation of osteoclast differentiation and function by the new members of the tumor necrosis factor receptor and ligand families. Endocr Rev 20(3):345–357

    Article  CAS  PubMed  Google Scholar 

  • Sugihara T, Okiyama N, Suzuki M, Kohyama K, Matsumoto Y, Miyasaka N, Kohsaka H (2010) Definitive engagement of cytotoxic CD8 T cells in C protein-induced myositis, a murine model of polymyositis. Arthritis Rheum 62(10):3088–3092

    Article  PubMed  Google Scholar 

  • Sugiura T, Kawaguchi Y, Harigai M, Takagi K, Ohta S, Fukasawa C, Hara M, Kamatani N (2000) Increased CD40 expression on muscle cells of polymyositis and dermatomyositis: role of CD40-CD40 ligand interaction in IL-6, IL-8, IL-15, and monocyte chemoattractant protein-1 production. J Immunol 164(12):6593–6600

    Article  CAS  PubMed  Google Scholar 

  • Szekanecz Z, Koch AE (2016) Successes and failures of chemokine-pathway targeting in rheumatoid arthritis. Nat Rev Rheumatol 12(1):5–13

    Article  CAS  PubMed  Google Scholar 

  • Takatori H, Kanno Y, Chen Z, O'Shea JJ (2008) New complexities in helper T cell fate determination and the implications for autoimmune diseases. Mod Rheumatol 18(6):533–541

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Takayanagi H (2007) Osteoimmunology: shared mechanisms and crosstalk between the immune and bone systems. Nat Rev Immunol 7(4):292–304

    Article  CAS  PubMed  Google Scholar 

  • Takayanagi H (2012) New developments in osteoimmunology. Nat Rev Rheumatol 8(11):684–689

    Article  CAS  PubMed  Google Scholar 

  • Takayanagi H, Iizuka H, Juji T, Nakagawa T, Yamamoto A, Miyazaki T, Koshihara Y, Oda H, Nakamura K, Tanaka S (2000a) Involvement of receptor activator of nuclear factor κB ligand/osteoclast differentiation factor in osteoclastogenesis from synoviocytes in rheumatoid arthritis. Arthritis Rheum 43(2):259–269

    Article  CAS  PubMed  Google Scholar 

  • Takayanagi H, Kim S, Koga T, Nishina H, Isshiki M, Yoshida H, Saiura A, Isobe M, Yokochi T, Inoue J, Wagner EF, Mak TW, Kodama T, Taniguchi T (2002) Induction and activation of the transcription factor NFATc1 (NFAT2) integrate RANKL signaling in terminal differentiation of osteoclasts. Dev Cell 3(6):889–901

    Article  CAS  PubMed  Google Scholar 

  • Takayanagi H, Ogasawara K, Hida S, Chiba T, Murata S, Sato K, Takaoka A, Yokochi T, Oda H, Tanaka K, Nakamura K, Taniguchi T (2000b) T cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-γ. Nature 408(6812):600–605

    Article  CAS  PubMed  Google Scholar 

  • Tat SK, Pelletier JP, Velasco CR, Padrines M, Martel-Pelletier J (2009) New perspective in osteoarthritis: the OPG and RANKL system as a potential therapeutic target? Keio J Med 58(1):29–40

    Article  CAS  PubMed  Google Scholar 

  • Taubman MA, Kawai T (2001) Involvement of T-lymphocytes in periodontal disease and in direct and indirect induction of bone resorption. Crit Rev Oral Biol Med 12(2):125–135

    Article  CAS  PubMed  Google Scholar 

  • Teitelbaum SL, Ross FP (2003) Genetic regulation of osteoclast development and function. Nat Rev Genet 4(8):638–649

    Article  CAS  PubMed  Google Scholar 

  • Teng F, Klinger CN, Felix KM, Bradley CP, Wu E, Tran NL, Umesaki Y, Wu HJ (2016) Gut microbiota drive autoimmune arthritis by promoting differentiation and migration of Peyer's patch T follicular helper cells. Immunity 44(4):875–888

    Article  CAS  PubMed  Google Scholar 

  • Teramachi J, Kukita A, Li YJ, Ushijima Y, Ohkuma H, Wada N, Watanabe T, Nakamura S, Kukita T (2011) Adenosine abolishes MTX-induced suppression of osteoclastogenesis and inflammatory bone destruction in adjuvant-induced arthritis. Lab Invest 91(5):719–731

    Article  CAS  PubMed  Google Scholar 

  • Thieblemont N, Wright HL, Edwards SW, Witko-Sarsat V (2016) Human neutrophils in auto-immunity. Semin Immunol 28(2):159–173

    Article  CAS  PubMed  Google Scholar 

  • Thomssen H, Hoffmann B, Schank M, Elewaut D, Meyer zum Buschenfelde KH, Marker-Hermann E (2000) There is no disease-specific role for streptococci-responsive synovial T lymphocytes in the pathogenesis of psoriatic arthritis. Med Microbiol Immunol 188(4):203–207

    CAS  PubMed  Google Scholar 

  • Thorleifsdottir RH, Sigurdardottir SL, Sigurgeirsson B, Olafsson JH, Sigurdsson MI, Petersen H, Arnadottir S, Gudjonsson JE, Johnston A, Valdimarsson H (2012) Improvement of psoriasis after tonsillectomy is associated with a decrease in the frequency of circulating T cells that recognize streptococcal determinants and homologous skin determinants. J Immunol 188(10):5160–5165

    Article  CAS  PubMed  Google Scholar 

  • Udagawa N, Takahashi N, Yasuda H, Mizuno A, Itoh K, Ueno Y, Shinki T, Gillespie MT, Martin TJ, Higashio K, Suda T (2000) Osteoprotegerin produced by osteoblasts is an important regulator in osteoclast development and function. Endocrinology 141(9):3478–3484

    Google Scholar 

  • Udalova IA, Mantovani A, Feldmann M (2016) Macrophage heterogeneity in the context of rheumatoid arthritis. Nat Rev Rheumatol 12(8):472–485

    Article  CAS  PubMed  Google Scholar 

  • Valesini G, Gerardi MC, Iannuccelli C, Pacucci VA, Pendolino M, Shoenfeld Y (2015) Citrullination and autoimmunity. Autoimmun Rev 14(6):490–497

    Article  CAS  PubMed  Google Scholar 

  • van de Sande MG, Baeten DL (2016) Immunopathology of synovitis: from histology to molecular pathways. Rheumatology (Oxford) 55(4):599–606

    Article  Google Scholar 

  • van den Broek MF, van Bruggen MC, Koopman JP, Hazenberg MP, van den Berg WB (1992) Gut flora induces and maintains resistance against streptococcal cell wall-induced arthritis in F344 rats. Clin Exp Immunol 88(2):313–317

    Article  PubMed Central  PubMed  Google Scholar 

  • Vattemi G, Mirabella M, Guglielmi V, Lucchini M, Tomelleri G, Ghirardello A, Doria A (2014) Muscle biopsy features of idiopathic inflammatory myopathies and differential diagnosis. Auto Immun Highlights 5(3):77–85

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Viner NJ, Bailey LC, Life PF, Bacon PA, Gaston JS (1991) Isolation of Yersinia-specific T cell clones from the synovial membrane and synovial fluid of a patient with reactive arthritis. Arthritis Rheum 34(9):1151–1157

    Article  CAS  PubMed  Google Scholar 

  • Vingsbo C, Sahlstrand P, Brun JG, Jonsson R, Saxne T, Holmdahl R (1996) Pristane-induced arthritis in rats: a new model for rheumatoid arthritis with a chronic disease course influenced by both major histocompatibility complex and non-major histocompatibility complex genes. Am J Pathol 149(5):1675–1683

    CAS  PubMed Central  PubMed  Google Scholar 

  • Walsh MC, Choi Y (2014) Biology of the RANKL-RANK-OPG system in immunity, bone, and beyond. Front Immunol 5:511

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Wang Q, Vasey FB, Mahfood JP, Valeriano J, Kanik KS, Anderson BE, Bridgeford PH (1999) V2 regions of 16S ribosomal RNA used as a molecular marker for the species identification of streptococci in peripheral blood and synovial fluid from patients with psoriatic arthritis. Arthritis Rheum 42(10):2055–2059

    Article  CAS  PubMed  Google Scholar 

  • Wechalekar MD, Smith MD (2014) Utility of arthroscopic guided synovial biopsy in understanding synovial tissue pathology in health and disease states. World J Orthop 5(5):566–573

    Article  PubMed Central  PubMed  Google Scholar 

  • Wen-Jing L, Chuan-Qiang P, Hong-Hua L, Xiang-Hui L, Jie-Xiao L (2015) A new modified animal model of myosin-induced experimental autoimmune myositis enhanced by defibrase. Arch Med Sci 11(6):1272–1278

    Article  PubMed Central  PubMed  Google Scholar 

  • Wiendl H, Hohlfeld R, Kieseier BC (2005a) Immunobiology of muscle: advances in understanding an immunological microenvironment. Trends Immunol 26(7):373–380

    Article  CAS  PubMed  Google Scholar 

  • Wiendl H, Hohlfeld R, Kieseier BC (2005b) Muscle-derived positive and negative regulators of the immune response. Curr Opin Rheumatol 17(6):714–719

    Article  CAS  PubMed  Google Scholar 

  • Wilder RL, Remmers EF, Kawahito Y, Gulko PS, Cannon GW, Griffiths MM (1999) Genetic factors regulating experimental arthritis in mice and rats. In: Theofilopoulos AN (ed) Genes and genetics of autoimmunity: current directions in autoimmunity, 1st edn. Karger, Basel, pp 121–165

    Chapter  Google Scholar 

  • Wong BR, Rho J, Arron J, Robinson E, Orlinick J, Chao M, Kalachikov S, Cayani E, Bartlett FSI, Frankel WN, Lee SY, Choi Y (1997) TRANCE is a novel ligand of the tumor necrosis receptor family that activates c-Jun N-terminal kinase in T cells. J Biol Chem 272(40):25190–25194

    Article  CAS  PubMed  Google Scholar 

  • Yago T, Nanke Y, Kawamoto M, Furuya T, Kobashigawa T, Kamatani N, Kotake S (2007) IL-23 induces human osteoclastogenesis via IL-17 in vitro, and anti-IL-23 antibody attenuates collagen-induced arthritis in rats. Arthritis Res Ther 9(5):R96

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K, Kuriyama M, Kanno T, Murakami A, Tsuda E, Morinaga T, Higashio K (1998a) Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG/OCIF inhibits osteoclastogenesis in vitro. Endocrinology 139(3):1329–1337

    PubMed  Google Scholar 

  • Yasuda H, Shima N, Nakagawa N, Yamaguchi K, Kinosaki M, Mochizuki S, Tomoyasu A, Yano K, Goto M, Murakami A, Tsuda E, Morinaga T, Higashio K, Udagawa N, Takahashi N, Suda T (1998b) Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci U S A 95(7):3597–3602

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yu M, Cavero V, Lu Q, Li H (2015) Follicular helper T cells in rheumatoid arthritis. Clin Rheumatol 34(9):1489–1493

    Article  PubMed  Google Scholar 

  • Zhang J, Niu C, Ye L, Huang H, He X, Tong WG, Ross J, Haug J, Johnson T, Feng JQ, Harris S, Wiedemann LM, Mishina Y, Li L (2003) Identification of the haematopoietic stem cell niche and control of the niche size. Nature 425(6960):836–841

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Jordan JM (2010) Epidemiology of osteoarthritis. Clin Geriatr Med 26(3):355–369

    Article  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. GEMpath Inc., 1100 East 17th Avenue, Unit M202, Longmont, CO, 80504-3715, USA

    Brad Bolon DVM,MS,PhD,DACVP,DABT,FATS,FIATP

  2. Takeda Pharmaceuticals International Co., 35 Landsdowne Street, Cambridge, MA, 02139, USA

    Jairo Nunes D.V.M., M.S., Ph.D., D.ACVP

Authors
  1. Brad Bolon DVM,MS,PhD,DACVP,DABT,FATS,FIATP
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jairo Nunes D.V.M., M.S., Ph.D., D.ACVP
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Brad Bolon DVM,MS,PhD,DACVP,DABT,FATS,FIATP .

Editor information

Editors and Affiliations

  1. Charles River Laboratories, Inc., Durham, North Carolina, USA

    George A. Parker

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Bolon, B., Nunes, J. (2017). Immunopathology of the Musculoskeletal System. In: Parker, G. (eds) Immunopathology in Toxicology and Drug Development. Molecular and Integrative Toxicology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-47385-7_12

Download citation

Publish with us

Policies and ethics

Search

Navigation