Regulation of postnatal bone homeostasis by TGFβ.

Perhaps more so than any other tissue, bone has pivotal mechanical and biological functions. Underlying the ability of bone to execute these functions, whether providing structural support or preserving mineral homeostasis, is the dynamic remodeling of bone matrix. Cells within bone integrate multiple stimuli to balance the deposition and resorption of bone matrix. Transforming growth factor-β (TGFβ) uniquely coordinates bone cell activity to maintain bone homeostasis. TGFβ regulates the differentiation and function of both osteoblasts and osteoclasts, from lineage recruitment to terminal differentiation, to balance bone formation and resorption. TGFβ calibrates the synthesis and material quality of bone matrix and bone's responsiveness to applied mechanical loads. Therefore, by coupling the activity of bone forming and resorbing cells, and by sensing, responding to and defining physical cues, TGFβ integrates physical and biochemical stimuli to maintain bone homeostasis. Disruption of TGFβ signaling has significant consequences on bone mass and quality. Alternatively, TGFβ is a powerful lever that has the potential to yield therapeutic benefit in cases where bone homeostasis needs to be recalibrated.