This chapter describes the role of bone matrix as a repository of growth, and morphogenetic factors, including bone morphogenetic proteins. Demineralized bone matrix is the initial starting biomaterial for isolation, purification and molecular cloning, and expression of bone morphogenetic proteins (BMPs). There are 15 members of the BMP family in humans, and they have wide-ranging actions on tissues beyond bone. The action of BMPs is mediated by receptors for BMPs. The type I and II BMP receptors bind BMPs, and the activated receptors phosphorylate intracellular substrates, called Smads. The term Smad is a fusion of two genes Sma in worms, and a human homolog of a Drosophila gene Mad (mothers against decapentaplegic). BMP receptors phosphorylate Smads 1, 5, and 8 in cytoplasm. Upon phosphorylation they enter the nucleus in partnership with a common partner Smad 4, and turn on the gene expression. The bioavailability of BMPs for receptor binding is influenced by BMP-binding proteins such as noggin and chordin, and interactions with extracellular matrix components, such as type W collagen and heparan sulfate. BMPs may have potential clinical utility in fracture healing, spine fusion, reconstructive surgery, oral surgery, and plastic surgery.
ASJC Scopus subject areas
- Immunology and Microbiology(all)