Biochemical and molecular mediators of bone metabolism

Bone is continually remodeled by the coupled actions of osteoclasts and 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. Osteoclasts appear to be the effector cells in the resorptive process with the capacity to both dissolve the mineral by proton pumps which lower the local pH as well as to hydrolyze the organic matrix by secreted enzymes. Osteoblasts, however, also are involved in the regulation of osteoclastic cell activity and may thus prime bone surfaces by changes 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 involved in the regulation of osteoclastogenesis. The osteoblast-like cells also appear to have specific receptors for resorptive agents and mediate their effects via a series of intracellular responses. One pathway involves cyclic 3', 5' adenosine monophosphate (cyclic AMP) and the second involves membrane phospholipids, diacylglycerol, protein kinase C, and cytosolic calcium. There is also emerging evidence that proto-oncogenes may be involved in regulation of the proliferation and eventual 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 metabolism.