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Bone morphogenetic protein receptors and their nuclear effectors in bone formation

  • Chapter
Bone Morphogenetic Proteins

Part of the book series: Progress in Inflammation Research ((PIR))

Abstract

Pioneering studies on the ability of extracts from decalcified bone matrix to promote ectopic bone and cartilage formation [1] led to searches for the identity of these morphogens which define skeletal patterning. With the advent of powerful methods for protein purification, capability to determine amino acid sequences on small amounts of protein and DNA cloning, bone morphogenetic proteins (BMPs) were discovered [2–4]. The amino acid sequences predicted from their cDNA sequences revealed that BMP-2, BMP-3 and BMP-4 (BMP-1 is a member of the astacin family of metalloproteases) are members of the TGF-13 superfamily, which also includes the TGF-βs and activins [5]. Mainly through their sequence homology with other BMPs approximately 20 members in the BMP subgroup have now been identified and can be divided in multiple groups of structurally related proteins, e.g. BMP2 and BMP-4 are highly related, BMP-6, BMP-7 and BMP-8 form another subgroup, and growth and differentiation factor (GDF)-5 (also termed cartilage-derived morphogenetic protein (CDMP)-1, GDF-7 (also termed CDGF-2) and GDF-6 are similar to each other.In vitroBMPs were found to have potent effects on various cells implicated in cartilage and bone formation, e.g. induce proteoglycan synthesis in chondroblasts and stimulate alkaline phosphatase activity and type I collagen synthesis in osteoblasts [4]. When injected into muscle of rats, BMPs can induce a biological cascade of cellular events leading to ectopic bone formation [3, 4]. GDF-5, GDF-6 and GDF-7 induce more efficiently tendon and cartilage-like structures[6, 7]. Preclinical studies of certain BMPs in primates and other mammals have demonstrated their effectiveness in restoring large segmental bone defects [8, 9].

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  1. Division of Cellular Biochemistry, The Netherland Cancer Institute, Plesmanlaan 121, 1066, CX, Amsterdam, The Netherlands

    Olexander Korchynsky & Peter ten Dijke

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  1. School of Medicine, Laboratory for Mineralized Tissues, Salata 11, Zagreb, 10000, Croatia

    Slobodan Vukicevic

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    Kuber T. Sampath

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Korchynsky, O., Dijke, P.t. (2002). Bone morphogenetic protein receptors and their nuclear effectors in bone formation. In: Vukicevic, S., Sampath, K.T. (eds) Bone Morphogenetic Proteins. Progress in Inflammation Research. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8121-0_3

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