Bone-derived factors active on bone cells.

Effects of systemic calcium regulating hormones have been studied extensively, yet mechanisms of bone volume regulation at the local level are poorly understood. Our laboratory has reported evidence for two locally mediated processes of bone volume regulation which function independently of systemic control: (1) coupling of bone formation and resorption and (2) repletion of resorbed bone. These local regulatory mechanisms have been shown to occur in vivo and in vitro. We have reported that embryonic chick tibiae in culture, stimulated to resorb, release a factor in the serum-free culture medium that stimulates bone cell proliferation and bone matrix formation in vitro. We have postulated that this factor could be involved in the coupling mechanism. Subsequently, a similar factor which stimulates bone cell proliferation, collagen synthesis and bone formation in vitro was extracted from embryonic and adult bones. The factor partially purified from human bone, designated as human skeletal growth factor, has molecular weight, heat sensitivity and biological activity similar to the factor found in bone conditioned medium. Many other biologically active factors have also been extracted from bone cells or demineralized bone by different laboratories. Their actions on bone cells range from chemotactic to mitogenic. These recently discovered bone factors emphasize that there is important regulation of bone metabolism at the local level.