The Multifaceted Effects of Osteocytic TGFβ Signaling on the Skeletal and Extraskeletal Functions of Bone

To summarize the fundamental role of transforming growth factor beta (TGFβ) signaling in osteocytes and highlight the physiological and pathophysiological conditions stemming from the deregulation of this pathway in osteocytes.

Osteocytes perform a myriad of skeletal and extraskeletal functions, including mechanosensing, coordinating bone remodeling, local bone matrix turnover, and maintaining systemic mineral homeostasis and global energy balance. Transforming growth factor-beta (TGFβ) signaling, which is crucial for embryonic and postnatal bone development and maintenance, has been found to be essential for several osteocyte functions. There is some evidence that TGFβ might be accomplishing these functions through crosstalk with the Wnt, PTH, and YAP/TAZ pathways in osteocytes, and a better understanding of this complex molecular network can help identify the pivotal convergence points responsible for distinct osteocyte functions. This review provides recent updates on the interwoven signaling cascades coordinated by TGFβ signaling within osteocytes to support their skeletal and extraskeletal functions and highlights physiological and pathophysiological conditions implicating the role of TGFβ signaling in osteocytes.