Mechanisms by which cells of the osteoblast lineage control osteoclast formation and activity

The cells of bone are of two lineages, the osteoblasts arising from pluripotential mesenchymal cells and osteoclasts from hemopoietic precursors of the monocyte-macrophage series. Resorption of bone by the multinucleate osteoclast requires the generation of new osteoclasts and their activation. Many hormones and cytokines are able to promote bone resorption by influencing these processes, but they achieve this without acting directly on osteoclasts. Most evidence indicates that their actions are mediated by cells of the osteoblast lineage. Evidence for hormone- and cytokine-induced activation of osteoclasts requiring the mediation of osteoblasts comes from studies of resorption by isolated osteoclasts. However, consistent evidence for a specific "activating factor" is lacking, and the argument is presented that the isolated osteoclast resorption assays have not been shown convincingly to be assays of osteoclast activation. The view is presented that osteoblast-mediated osteoclast activation is the result of several events in the microenvironment without necessarily requiring the existence of a specific, essential osteoclast activator. On the other hand, a specific promoter of osteoclast differentiation does seem likely to be a product of cells of the stromal/osteoblast series. Evidence in favour of this comes from studies of osteoclast generation in co-cultures of osteoblast/stromal cells with hemopoietic cells. Conflicting views, maintaining that osteoclasts can develop from hemopoietic cells without stromal intervention, might be explained by varying criteria used in identification of osteoclasts. Osteoblastic and osteoclastic renewal, and the interactions of these lineages, are central to the process of bone remodeling.