ROLE OF COLONY-STIMULATING FACTOR-I IN BONE METABOLISM

Colony-stimulating factor-1 (CSF-1) is a cytokine required for prolife ration, differentiation, activity, and survival of cells of the mononu clear phagocytic system. The growth factor is synthesized as a soluble , matrix, or membrane associated molecule. The specific functions of t hese forms are not clear. However, some data suggest a dependence of t he development of various populations of tissue macrophages on the loc ally expressed and presented cytokine. Deficiency in CSF-1, as is the case in the murine mutant strain op/op, results in low numbers of macr ophages and monocytes and, most striking, leads to osteopetrosis due t o a virtual absence of osteoclasts. Using the op/op mutation as a mode l, CSF-1 was established as one of the growth factors for osteoclasts. The expression of CSF-1 receptors, encoded by the proto-oncogene c-fm s, by osteoclast precursors and osteoclasts, suggested an effect of th is cytokine not only during osteoclast formation but also on the matur e cells. In fact, CSF-1 was shown to inhibit the resorbing activity, t o stimulate migration, and to support survival of isolated osteoclasts in vitro. By these actions on cells of the osteoclast lineage, CSF-1 induces recruitment of new osteoclasts, leading to a net increase of b one resorption, and might govern the spatial distribution of resorptio n sites within the bone. During these processes, locally expressed and presented forms of the growth factor may play a crucial role, as will be discussed in this article. (C) 1994 Wiley-Liss, Inc.