Abstract
Members of the ephrin and Eph family are local mediators of cell function through largely contact-dependent processes in development and in maturity. Production of ephrinB2 mRNA and protein are increased by PTH and PTHrP in osteoblasts. Both a synthetic peptide antagonist of ephrinB2/EphB4 receptor interaction and recombinant soluble extracellular domain of EphB4 (sEphB4), which is an antagonist of both forward and reverse EphB4 signaling, were able to inhibit mineralization and the expression of several osteoblast genes involved late in osteoblast differentiation. The findings are consistent with ephrinB2/EphB4 signaling within the osteoblast lineage having a paracrine role in osteoblast differentiation, in addition to the proposed role of osteoclast-derived ephrinB2 in coupling of bone formation to resorption. This local regulation might contribute to control of osteoblast differentiation and bone formation at remodeling sites, and perhaps also in modeling.
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References
Allan, E.H., Hausler, K.D., Wei, T., Gooi, J.H., Quinn, J.M., Crimeen-Irwin, B., Pompolo, S., Sims, N.A., Gillespie, M.T, Onyia, J.E., & Martin, T.J. (2008). EphrinB2 Regulation by Parathyroid Hormone (PTH) and PTHrP Revealed by Molecular Profiling in Differentiating Osteoblasts. J Bone Miner Res, 23(8), 1170–1181.
Bonewald, L.F. (2007). Osteocyte messages from a bony tomb. Cell Metab, 5(6), 410–411.
Centrella, M., McCarthy, T.L., & Canalis, E. (1991). Transforming growth factor-beta and remodeling of bone. J Bone Joint Surg Am, 73(9), 1418–1428.
Civitelli, R. (2008). Cell-cell communication in the osteoblast/osteocyte lineage. Arch Biochem Biophys, 473(2), 188–192.
Compagni, A., Logan, M., Klein, R., & Adams, R.H. (2003). Control of skeletal patterning by ephrinB1-EphB interactions. Dev Cell, 5(2), 217–230.
Everts, V., Delaisse, J.M., Korper, W., Jansen, D.C., Tigchelaar-Gutter, W., Saftig, P., & Beertsen, W. (2002). The bone lining cell: its role in cleaning Howship’s lacunae and initiating bone formation. J Bone Miner Res, 17(1), 77–90.
Gray, C., Boyde, A., & Jones, S.J. (1996). Topographically induced bone formation in vitro: implications for bone implants and bone grafts. Bone, 18(2), 115–123.
Hamada, K., Oike, Y., Ito, Y., Maekawa, H., Miyata, K., Shimomura, T., & Suda, T. (2003). Distinct roles of ephrin-B2 forward and EphB4 reverse signaling in endothelial cells. Arterioscler Thromb Vasc Biol, 23(2), 190–197.
Himanen, J.P., Chumley, M.J., Lackmann, M., Li, C., Barton, W.A., Jeffrey, P.D., Vearing, C., Geleick, D., Feldheim, D.A., Boyd, A.W., Henkemeyer, M., & Nikolov, D.B. (2004). Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling. Nat Neurosci, 7(5):501–509.
Himanen, J.P., & Nikolov, D.B. (2003). Eph receptors and ephrins. Int J Biochem Cell Biol, 35(2), 130–134.
Holmberg, J., Armulik, A., Senti, K.A., Edoff, K., Spalding, K., Momma, S., Cassidy, R., Flanagan, J.G., & Frisen, J. (2005). Ephrin-A2 reverse signaling negatively regulates neural progenitor proliferation and neurogenesis. Genes Dev, 19(4), 462–471.
Kertesz, N., Krasnoperov, V., Reddy, R., Leshanski, L., Kumar, S.R., Zozulya, S., & Gill, P.S. (2006). The soluble extracellular domain of EphB4 (sEphB4) antagonizes EphB4-EphrinB2 interaction, modulates angiogenesis, and inhibits tumor growth. Blood, 107(6), 2330–2338.
Koolpe, M., Burgess, R., Dail, M., & Pasquale, E.B. (2005). EphB receptor-binding peptides identified by phage display enable design of an antagonist with ephrin-like affinity. J Biol Chem, 280(17), 17301–17311.
Lips, P., Courpron, P., & Meunier, P.J. (1978). Mean wall thickness of trabecular bone packets in the human iliac crest: changes with age. Calcif Tissue Res, 26(1), 13–17.
Lu Q, Sun E.E., Klein R.S., Flanagan J.G. (2001). Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively inhibits G protein-coupled chemoattraction. Cell, 105(1), 69–79.
Miao, D., He, B., Jiang, Y., Kobayashi, T., Soroceanu, M.A., Zhao, J., Su, H., Tong, X., Amizuka, N., Gupta, A., Genant, H.K., Kronenberg, H.M., Goltzman, D., & Karaplis, A.C. (2005). Osteoblast-derived PTHrP is a potent endogenous bone anabolic agent that modifies the therapeutic efficacy of administered PTH 1-34. J Clin Invest, 115(9), 2402–2411.
Mohan, S., & Baylink, D.J. (1991). Bone growth factors. Clin Orthop Relat Res, 263, 30–48.
Murai, K.K., & Pasquale, E.B. (2003). 'Eph’ective signaling: forward, reverse and crosstalk. J Cell Sci, 116(Pt 14), 2823–2832.
Nakamura, M., Udagawa, N., Matsuura, S., Mogi, M., Nakamura, H., Horiuchi, H., Saito, N., Hiraoka, B.Y., Kobayashi, Y., Takaoka, K., Ozawa, H., Miyazawa, H., & Takahashi, N. (2003). Osteoprotegerin regulates bone formation through a coupling mechanism with bone resorption. Endocrinology, 144(12), 5441–5449.
Noble, B.S., Peet, N., Stevens, H.Y., Brabbs, A., Mosley, J.R., Reilly, G.C., Reeve, J., Skerry, T.M., & Lanyon, L.E. (2003). Mechanical loading: biphasic osteocyte survival and targeting of osteoclasts for bone destruction in rat cortical bone. Am J Physiol Cell Physiol, 284(4), C934–C943.
Oreffo, R.O., Mundy, G.R., Seyedin, S.M., & Bonewald, L.F. (1989). Activation of the bone-derived latent TGF beta complex by isolated osteoclasts. Biochem Biophys Res Commun, 158(3), 817–823.
Parfitt, A.M. (1996). Skeletal heterogeneity and the purposes of bone remodeling: implications for the understanding of osteoporosis. In: Marcus R, Feldman D, Kelsey J (eds.) Osteoporosis. Academic Press, San Diego, CA, pp. 315–339.
Parfitt, A.M. (2002). Targeted and nontargeted bone remodeling: relationship to basic multicellular unit origination and progression. Bone, 30(1), 5–7.
Pasquale, E.B. (2005). Eph receptor signaling [stet] casts a wide net on cell behaviour. Nat Rev Mol Cell Biol, 66, 462–475.
Robling, A.G., Bellido, T., & Turner, C.H. (2006). Mechanical stimulation in vivo reduces osteocyte expression of sclerostin. J Musculoskelet Neuronal Interact, 6(4), 354.
Sims, N.A., Jenkins, B.J., Quinn, J.M., Nakamura, A., Glatt, M., Gillespie, M.T., Ernst, M., & Martin, T.J. (2004). Glycoprotein 130 regulates bone turnover and bone size by distinct downstream signaling pathways. J Clin Invest, 113(3), 379–389.
Suda, T., Takahashi, N., Udagawa, N., Jimi, E., Gillespie, M.T., & Martin, T.J. (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.
van Bezooijen, R.L., ten Dijke, P., Papapoulos, S.E., & Lowik, C.W. (2005). SOST/sclerostin, an osteocyte-derived negative regulator of bone formation. Cytokine Growth Factor Rev, 16(3), 319–327.
Yancopoulos, G.D., Davis, S., Gale, N.W., Rudge, J.S., Wiegand, S.J., & Holash, J. (2000). Vascular-specific growth factors and blood vessel formation. Nature, 407(6801), 242–248.
Zhao, C., Irie, N., Takada, Y., Shimoda, K., Miyamoto, T., Nishiwaki, T., Suda, T., & Matsuo, K. (2006). Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis. Cell Metab, 4(2), 111–121.
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Martin, T. et al. (2009). Communication Between EphrinB2 and EphB4 Within the Osteoblast Lineage. In: Choi, Y. (eds) Osteoimmunology. Advances in Experimental Medicine and Biology, vol 658. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-1050-9_6
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DOI: https://doi.org/10.1007/978-1-4419-1050-9_6
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