STRUCTURE AND MOLECULAR REGULATION OF BONE-MATRIX PROTEINS

The organic matrix of bone contains several protein families, includin g collagens, proteoglycans, and glycoproteins, all of which may be ext ensively modified by posttranslational events, such as phosphorylation and sulfation. Many of the glycoproteins contain Arg-Gly-Asp (RGD), t he integrin-binding sequence, within their structure, whereas other co nstituent proteins contain gamma-carboxyglutamic acid. The deposition of bone matrix by cells in the osteoblastic lineage is regulated by ex trinsic factors, such as systemic and local growth factors and physica l forces, and factors that are intrinsic to the cell, such as position in the cell cycle, maturational stage, and developmental age of the d onor. Recent studies of several bone matrix gene promoters have identi fied cis- and trans-acting elements that are responsible for gene acti vity, although the precise sequence of regulatory events is not known. Development of in vitro assays, coupled with studies of the appearanc e of these proteins during development in vivo, provides insight into the functions of these proteins during the various stages of bone meta bolism. Potential roles for these proteins include proliferation and m aturation of stem cells, formation of matrix scaffolding elaborated by bone-forming cells, modeling, and remodeling. Changes in the function al properties of the extracellular matrix may be involved in a variety of disease processes, including osteoporosis and oral bone loss.