Interleukin-1 Beta is a Potent Inhibitor of Bone Formation in Vitro

The effect of interleukin-1 beta, the major component of osteoclast-activating factor (OAF), on bone formation by fetal rat osteoblast-rich cells was investigated. An in vitro culture system developed by Ecarot-Charrier et al. (1983) and Bellows et al. (1986) was utilized in which osteoblasts form mineralized nodules which closely resemble woven bone. Continuous exposure of cultures to homogenous IL-1 beta resulted in potent inhibition of mineralized nodule formation, which was half maximal at 0.1 U/ml (7.5 X 10(-13) M). Bone formation may thus be considerably more sensitive to IL-1 beta than is bone resorption (half maximal at 3.8 X 10(-11) M). Inhibition of bone formation occurred when cultures were exposed to IL-1 beta at both early and late time periods and was unaffected by the presence of indomethacin or by the osteoclast inhibitors calcitonin and gamma-interferon. Instead, IL-1 beta exerted multiple inhibitory effects on osteoblast functions, including inhibition of collagen and noncollagen protein synthesis, alkaline phosphatase expression, and cell replication. On a dose response basis, the inhibition of protein synthesis correlated most closely with inhibition of bone formation. IL-1 beta is clearly inhibitory rather than stimulatory for bone formation as assessed in this system and is therefore unlikely to function as a coupling factor linking the processes of bone resorption and bone formation.