Role of nitric oxide in the regulation of osteoblast metabolism.

Nitric oxide has recently been shown to inhibit the proliferation of several types of cells, including osteoclasts. Both osteoclasts and osteoblasts have inducible nitric oxide synthase and produce nitric oxide. Although the direct effect of nitric oxide on osteoblasts in general and osteoblast proliferation in particular has not been delineated, the authors performed studies to clarify the role of nitric oxide on osteoblast proliferation and metabolism. Cultures of human osteoblasts were exposed to 0.1, 1.0, and 10 microM of the nitric oxide releasing agent 3-morpholino sydnonimine (SIN-1) for 7 days. Cells were evaluated for proliferation and production of alkaline phosphatase and osteocalcin. Osteoblasts exhibited decreased proliferation relative to control cultures at 1.0 and 10 microM concentrations of SIN-1 (p < 0.05). Concentrations of 1.0 and 10 microM of SIN-1 effected a decreased production of osteocalcin and alkaline phosphatase (p < 0.05). The results of these studies indicate that nitric oxide may play a critical role by which osteoblasts exhibit self-regulation of mineral metabolism.