title: The regulation of osteoclastic development and function.
abstract: Cells of the osteoblastic lineage exert a dominant influence on osteoclastic bone resorption. They form a communicating network of osteocytes, surface osteocytes and osteoblasts that seems well placed to monitor the structure and performance of bone and to judge where bone formation or resorption is appropriate. Osteoblasts produce prostaglandins (PGs) which strongly inhibit osteoclastic resorption. None of the agents that stimulate resorption in intact bone, such as parathyroid hormone (PTH), interleukin 1 (IL-1), 1,25-(OH)2 vitamin D3 (1,25-(OH)2D3) or tumour necrosis factors, affects isolated osteoclasts, but all induce osteoblastic cells to produce osteoclastic resorption stimulatory activity (ORSA) that acts directly on osteoclasts. Osteoblasts seem to initiate resorption as well as stimulating or inhibiting it. Contact with bone mineral appears to be necessary: osteoclasts resorb mineralized but not unmineralized bone. All bone surfaces are lined by unmineralized organic material. Osteoblastic cells secrete neutral proteases, including collagenase, in response to hormonal stimulators of bone resorption. Incubation of osteoblasts, in the presence of PTH, on such surfaces or preincubation of the bone with collagenase predisposes bone to osteoclastic resorption. Agents that stimulate resorption in organ cultures seem to share these osteoblast-mediated mechanisms for induction and stimulation of resorption but 1,25-(OH)2D3 stimulates it through an additional mechanism. We have found that osteoclasts can be induced from haemopoietic tissue (including haemopoietic spleen cells) in the presence of 1,25-(OH)2D3--PTH and IL-1 have no effect in this system. Because osteoclasts lack receptors for 1,25-(OH)2D3 these results suggest either that osteoclast precursors lose 1,25-(OH)2D3 receptors during differentiation, or that a 1,25-(OH)2D3-responsive accessory cell in bone marrow induces osteoclastic differentiation in the presence of 1,25-(OH)2D3.
authors.affiliation: Department of Histopathology, St George's Hospital Medical School, London, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: Chambers
mesh_terms: D000818:Animals; D001846:Bone Development; D001862:Bone Resorption; D010010:Osteoclasts / Q000166:cytology*; D010011:Osteocytes / Q000166:cytology