REGULATION OF BONE-FORMATION BY BONE MORPHOGENETIC PROTEINS AND OTHERGROWTH-FACTORS

Bone formation in adult humans is a complex and closely regulated proc ess, It usually occurs at sites of previous osteoclastic bone resorpti on, It also may occur in the growing long bones during endochondral bo ne formation, and appositional bone formation also can appear during g rowth and adolescence without prior local resorption, particularly on periosteal surfaces, The cellular events involved in bone formation in clude chemotaxis of osteoblast precursors; proliferation of committed osteoblast precursors; differentiation, including expression of growth regulatory factors and the structural proteins of bone, such as osteo calcin, osteopontin, and Type I collagen; and mineralization, It is cl ear that these cellular events must be under very tight regulatory con trol, They may all be modulated by systemic hormones, including the ca lciotropic hormones, parathyroid hormone and 1,25 dihydroxyvitamin D a nd other systemic hormones, such as the pituitary and thyroid hormones and sex steroids, but probably are modulated predominantly by local f actors or cytokines generated in the bone cell microenvironment.