Effects of cytokines on alkaline phosphatase and osteocalcin production, calcification and calcium release by human osteoblastic cells.

We examined the effect of TNF-alpha, IL-1 beta and IL-6 on alkaline phosphatase (ALP) and osteocalcin (OC) production, calcification and calcium (Ca) release in human osteoblastic cell cultures obtained from human periosteum. The cells were cultured with varying concentrations of cytokines for 3 days. TNF-alpha and IL-1 beta significantly inhibited ALP production, decreased cellular Ca content, and significantly enhanced 45Ca release in human osteoblastic cells. IL-6, on the other hand, significantly suppressed 45Ca release by osteoblastic cells. These cytokines did not influence the production of OC by osteoblastic cells. The results obtained suggest that TNF-alpha and IL-1 beta may inhibit bone formation and calcification and that the effects of IL-6 on osteoblastic cells may be different from those of TNF-alpha or IL-1 beta. These effects on osteoblastic cells may be one of the mechanisms by which bone loss occurs in patients with RA.