ROLE OF INTERLEUKIN-6 AND PROSTAGLANDINS IN THE EFFECT OF MONOCYTE-CONDITIONED MEDIUM ON OSTEOCLAST FORMATION

There is evidence suggesting some role of mononuclear cells at the res orptive site in bone remodeling. The possibility was therefore postula ted that these cells might provide some signal for osteoclast formatio n. We examined the effects of human monocyte-conditioned medium (CM) o n the formation of osteoclast-like cells from hemopoietic blast cells in the absence of stromal cells and unfractionated bone cells in the p resence of stromal cells. In both culture systems, the osteoclast-like cell formation induced by 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D-3] or human parathyroid hormone (PTH)-(1-34) was significantly inhibited by adding 20% CM. The effects of monocyte-derived local regulators of bone turnover on osteoclast-like cell formation induced by 1,25(OH)(2) D-3 or PTH were determined. Interleukin-g (IL-6) inhibited osteoclast- like cell formation in both culture systems, whereas prostaglandin (PG ) E(2) significantly inhibited the formation only in the hemopoietic b last cell culture. The inhibitory effect of CM on osteoclast-like cell formation from hemopoietic blast cells was not observed when CM was p repared from monocytes pretreated with indomethacin. The inhibitory ef fect of CM and IL-6 on osteoclast-like cell formation in both culture systems was blocked by adding neutralizing IL-6 antibody. The present study demonstrated that CM inhibited osteoclast-like cell formation in duced by 1,25(OH)(2)D-3 and PTH presumably through the action of local regulators of bone turnover, such as IL-6 and PG. Our findings thus p rovide additional evidence that mononuclear cells play an important ro le at the resorptive site in bone remodeling.