Subsequently, the coding sequences of additional BMPs were cloned based on amino acid sequence homology ( Celeste et al. The corresponding recombinant BMP proteins, including BMP-1, were capable of inducing formation of cartilage or bone in vivo. Although BMP-1 was found to be a novel metalloproteinase, BMP-2, -3, and -4 were novel members of the transforming growth factor β (TGF-β) family. Subsequently, Wozney and colleagues (1988) cloned cDNAs for human BMP-1 through BMP-4 using the peptide sequence information obtained.
However, the identity of the BMP activity remained elusive until Wang and colleagues reported the isolation of BMP activity from extracts of bovine bone as a single gel band followed by sequencing the peptides obtained from trypsin digestion of the band ( Wang et al. The factor(s) responsible for ectopic bone formation was named “bone morphogenetic protein,” because this activity was abolished by digestion with trypsin, a typical protease ( Urist and Strates 1971).
These findings postulated the presence of bioactive factor(s) in the demineralized bone matrix responsible for inducing bone formation. In 1965, Urist reported that demineralized bone matrix implanted in muscular tissues induces ectopic formation of cartilage and bone tissues with bone marrow ( Urist 1965). In 1889, Senn found that aseptic bone cavities can be healed by decalcified bone ( Senn 1889).
In this review, we describe biochemical properties and biological activities of BMP family members in development and diseases.Īlthough BMPs are now known to be multifunctional cytokines identified both in vertebrates and invertebrates, they were first discovered as proteins that induce ectopic bone formation. The bone morphogenetic protein (BMP) family of ligands plays important roles in a multitude of processes during embryonic development and adult homeostasis by regulating cellular lineage commitment, morphogenesis, differentiation, proliferation, and apoptosis of various types of cells throughout the body. Because deregulation of the BMP activity at multiple steps in signal transduction is linked to a wide variety of human diseases, therapeutic use of activators and inhibitors of BMP signaling will provide potential avenues for the treatment of the human disorders that are caused by hypo- and hyperactivation of BMP signals, respectively. Furthermore, BMP signals are finely tuned by various agonists and antagonists. BMPs and the related “growth and differentiation factors” (GDFs) are members of the transforming growth factor β (TGF-β) family, and transduce their signals through type I and type II serine–threonine kinase receptors and their intracellular downstream effectors, including Smad proteins. Bone morphogenetic proteins (BMPs), originally identified as osteoinductive components in extracts derived from bone, are now known to play important roles in a wide array of processes during formation and maintenance of various organs including bone, cartilage, muscle, kidney, and blood vessels.
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