To investigate whether mechanical deformation of osteoblasts exerts an influence upon parathyroid hormone (PTH)-induced bone resorption, the effect of medium conditioned by a statically stretched, osteoblast-enriched, bone cell population on PTH-induced osteoclast-like cell formation in mouse bone marrow cultures was examined. The conditioned medium of stretched cultures stimulated bone marrow cells to differentiate into tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells in the presence of 10-8 M PTH(1-34). The stimulatory effect of the conditioned medium was significant when the bone cells were stretched at a 2 mm deflection in the 90% subconfluent state. Conditioned medium from cultures in the 50% subconfluent stale failed to enhance osteoclast-like cell formation. PTH-induced, TRAP- positive multinuclear cells were decreased in number by the addition of stretch-conditioned medium in the postconfluent state. When 10(-6) M indomethacin was added to bone cell cultures during stretching, the resulting conditioned medium suppressed PTH-induced, TRAP-positive multinuclear cell formation. However, even if 10-8 M prostaglandin E2 was added to the stretched hone cell cultures along with the indomethacin, the resulting conditioned medium did not reverse the suppression of the PTH-induced, osteoclast-like cell formation. These findings suggest that bone resorption in response to continuous mechanical deformation is regulated by cells of the osteoblast lineage such as preosteoblasts, osteoblasts, bone lining cells and osteocytes in vivo, and that prostaglandins, but not prostaglandin E2, are involved in the stretch-enhanced, osteoclast-like cell formation.
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