INTERLEUKIN-10 SELECTIVELY INHIBITS OSTEOCLASTOGENESIS BY INHIBITING DIFFERENTIATION OF OSTEOCLAST PROGENITORS INTO PREOSTEOCLAST-LIKE CELLS IN RAT BONE-MARROW CULTURE SYSTEM

Recombinant human interleukin-10 (hIL-10) inhibited the formation of o steoclast-like multinucleated cells in rat whole bone marrow cultures. The effect of hIL-10 on the process of osteoclast formation was furth er examined, since the process of osteoclast formation includes the pr oliferation and the differentiation of osteoclast progenitors into mon onuclear preosteoclasts and the fusion of preosteoclasts into multinuc leated osteoclasts. In the nonadherent bone marrow cell culture system , which was free of stromal cells and formed preosteoslast-like cells, hIL-10 significantly inhibited the formation of preosteoclast-like ce lls even at a very low concentration (0.5 U/ml). The strong inhibition appeared even after treatment with hIL-10 for only the first 24 h of the culture. However, hIL-10 did not affect the fusion process of preo steoclast-like cells to form osteoclast-like multinucleated cells in t he rat coculture system of preosteoclast-like cells with primary osteo blasts. Furthermore, hIL-10 completely inhibited the colony Formation induced by granulocyte macrophage colony-stimulating Factor (GM-CSF). These findings suggest that the inhibition of osteoclastogenesis by hI L-10 started at the early stage of the differentiation of osteoclast p rogenitors to preosteoclasts. (C) 1995 Wiley-Liss, Inc.