Abstract
A rat calvarial cell model of osteoblast differentiation using the formation of bone nodules in vitro as an endpoint was used to assess the effects of IL‐1β on osteoblast differentiation. Short‐term treatment (2 days) with IL‐1β early in culture resulted in increased nodule number and size as well as calcium content in contrast to long‐term treatment (6 days) in cultures assessed at 10–12 days. This increase in bone formation was blocked by IL‐1 receptor antagonists. Short‐term treatment increased COX‐2, prostaglandin (PGE~2~), and iNOS production. Exogenous PGE~2~ with IL‐1β enhanced this effect. COX‐2 inhibitors, indomethacin and N‐39, blocked 50% of nodule formation. NO donor did not modify effects of IL‐1β, but iNOS inhibitor (1400W) partially blocked the effects. However, PGE~2~ and NO donors could not rescue the decreased nodule number resulting from long‐term IL‐1β treatment. The results of this study suggest a biphasic effect of IL‐1β on bone nodule formation activated by IL‐1β binding with IL‐1 receptors, and the anabolic effect of early short‐term treatment with IL‐1β is likely mediated by PGE without ruling out nitric oxide. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:958–964, 2010