Current insights into the role of transforming growth factor-β in bone resorption

Transforming growth factor-β (TGF-β) elicits a variety of effects on cellular proliferation and differentiation. The major repository for TGF-β is bone, where it possesses separate facilitative and suppressive actions on osteoclast differentiation and bone resorption. Without a direct enabling stimulus from TGF-β monocytes cannot form osteoclasts but instead follow macrophage differentiation pathways. This facilitative action depends on an ability to promote a state in which precursors are resistant to anti-osteoclastic inflammatory signals. Following the initiation of resorption TGF-β is released from bone matrix. This acts on osteoblasts to reduce the availability of the osteoclast differentiation factor, RANKL (receptor activator of NFκB ligand) and thereby indirectly limits further osteoclast formation. Thus TGF-β has a fundamental role in the control of bone resorption having actions that first allow monocytes to develop into osteoclasts then subsequently limiting the extent and duration of resorption after its release from the bone matrix.