BIOCHEMICAL AND MOLECULAR MEDIATORS OF BONE METABOLISM

BONE IS CONTINUALLY REMODELED BY THE COUPLED ACTIONS of osteoclasts an d osteoblasts. This cellular remodeling occurs in discrete packets of tissue and is regulated by both systemic and locally-produced factors such as arachidonic acid metabolites, growth factors, and cytokines. O steoclasts appear to be the effector cells in the resorptive process w ith the capacity to both dissolve the mineral by proton pumps which lo wer the local pH as well as to hydrolyze the organic matrix by secrete d enzymes. Osteoblasts, however, also are involved in the regulation o f osteoclastic cell activity and may thus prime bone surfaces by chang es in cellular morphology as well as mediate the effects of resorptive agents by post-receptor signal transduction mechanisms. Osteoblastic cells may produce a number of cytokine-like molecules which can be inv olved in the regulation of osteoclastogenesis. The osteoblast-like cel ls also appear to have specific receptors for resorptive agents and me diate their effects via a series of intracellular responses. One pathw ay involves cyclic 3', 5' adenosine monophosphate (cyclic AMP) and the second involves membrane phospholipids, diacylglycerol, protein kinas e C, and cytosolic calcium. There is also emerging evidence that proto -oncogenes may be involved in regulation of the proliferation and even tual differentiation of osseous cells. The primary goal of this paper is to present current studies and hypotheses involving the biochemical and molecular mechanisms involved in the regulation of bone metabolis m.