Bone marrow cells produce soluble factors that inhibit osteoclast activity

Cytokines that stimulate bone resorption are produced by cells found in bon e marrow. However, marrow cells produce multiple factors, some of which may be inhibitors of osteoclast differentiation or activity. Thus, it is not p ossible to predict a priori whether the mixture of factors produced by marr ow cells will have a net stimulatory or inhibitory effect on bone resorptio n. In this study, we showed that the net effect of whole marrow is to inhib it osteoclast activity induced by parathyroid hormone. Fractionation of the marrow revealed that the inhibitory activity was in the marrow fluid. Howe ver, conditioned media obtained from marrow cell cultures also inhibited os teoclast activity. Thus, it is likely that the inhibitory factors are produ ced in vivo by cells residing in the marrow. These inhibitory factors may r epresent a physiological regulatory process that plays an important role in maintaining the balance between bone resorption and formation. Because we have previously shown that interleukin-6 is one of the cytokines that parat hyroid hormone induces in osteoblastic cells to stimulate osteoclast activi ty, one potential mechanism by which the marrow-derived inhibitory factors might act is by preventing this production of interleukin-6. However, we fo und that the marrow cell-conditioned media do not inhibit the production or activity of interleukin-6. Thus, the inhibitory factors appear to block os teoclast activity through a mechanism that does not involve interleukin-6. Taken together, these results demonstrate the importance of factors that in hibit bone resorption and emphasize that the presence of cytokines that sti mulate bone resorption in conditions such as osteoporosis and orthopaedic i mplant loosening should be interpreted with caution unless evidence exists demonstrating their functional importance.