Biphasic effects of interleukin-1beta on osteoblast differentiation in vitro.
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-1beta on osteoblast differentiation. Short-term treatment (2 days) with IL-1beta 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-1beta enhanced this effect. COX-2 inhibitors, indomethacin and N-39, blocked 50% of nodule formation. NO donor did not modify effects of IL-1beta, 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-1beta treatment. The results of this study suggest a biphasic effect of IL-1beta on bone nodule formation activated by IL-1beta binding with IL-1 receptors, and the anabolic effect of early short-term treatment with IL-1beta is likely mediated by PGE without ruling out nitric oxide.
Lin
Fu-Hsiumg
FH
Department of Surgery, Division of Orthopedic Surgery, Duke University, Box 3312, Durham, North Carolina 27710, USA.
Chang
Jessica B
JB
McGuire
Michael H
MH
Yee
John A
JA
Brigman
Brian E
BE
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D012886:Skull / Q000166:cytology
D052246:Cyclooxygenase 2 Inhibitors; D053583:Interleukin-1beta; D020030:Nitric Oxide Donors; D017472:Receptors, Interleukin-1; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D015232:Dinoprostone; D007213:Indomethacin