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IL-6 is produced by osteoblasts and induces bone resorption.
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1990
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The study aimed to determine whether IL‑6 participates in bone metabolism by measuring its mRNA expression in osteoblasts exposed to bone‑resorbing stimuli. MC3T3‑E1 and primary fetal mouse calvarial osteoblasts were cultured with systemic and local bone‑resorbing agents and IL‑6 mRNA levels were quantified. Local bone‑resorbing agents (IL‑1α, IL‑1β, TNF‑α, LPS) strongly induced IL‑6 mRNA and protein in both cell types, IL‑6 alone dose‑dependently stimulated bone resorption and osteoclastogenesis, and IL‑6 cooperated with IL‑1α to enhance resorption, while PTH had a modest effect and vitamin D did not alter IL‑6 expression, indicating osteoblast‑derived IL‑6 promotes bone resorption alone or synergistically with other agents.
To examine the possible involvement of IL-6 in bone metabolism, a mouse osteoblastic cell line (MC3T3-E1) and primary osteoblast-like cells from fetal mouse calvaria were cultured with several systemic and local bone-resorbing agents and their expression of IL-6 mRNA was determined. Local bone-resorbing agents such as IL-1 alpha, IL-1 beta, TNF-alpha, and LPS greatly induced IL-6 mRNA expression in both MC3T3-E1 cells and primary osteoblast-like cells. Parathyroid hormone slightly increased expression of IL-6 mRNA in primary osteoblast-like cells but not in MC3T3-E1 cells. Neither IL-6 nor 1 alpha,25-dihydroxyvitamin D3 increased expression of IL-6 mRNA in either of the osteoblast-like cells. In agreement with the expression of IL-6 mRNA, biologically active IL-6 was produced in response to the treatment with IL-1 alpha, TNF-alpha, and LPS in MC3T3-E1 cells. Adding IL-6 dose dependently stimulated the release of 45Ca from prelabeled fetal mouse calvaria. Simultaneously adding suboptimal concentrations of IL-6 and IL-1 alpha induced bone resorption cooperatively. In accord with the increase in the release of 45Ca by IL-6, there were three times as many osteoclasts in the bone sections of calvaria cultured with IL-6 for 5 days as in the controls. IL-6 slightly suppressed alkaline phosphatase activity and collagen synthesis in MC3T3-E1 cells. These results indicate that IL-6 is also produced by osteoblasts, preferentially in response to local bone-resorbing agents, and it induces bone resorption both alone and in concert with other bone-resorbing agents.