Cx43 and Mechanotransduction in Bone

Abstract

Bone adaptation to changes in mechanical stimuli occurs by adjusting bone formation and resorption by osteoblasts and osteoclasts, to maintain optimal bone mass. Osteocytes coordinate the actions of these cells on the bone surface by sensing mechanical forces and producing cytokines that increase or prevent osteoblast and osteoclast differentiation and function. Channels formed by connexins (Cxs) and, in particular, Cx43 in osteoblasts and osteocytes are central part of this mechanism to control bone mass. Cx43 hemichannels are opened by fluid flow and mediate the anti-apoptotic effect of mechanical stimulation in vitro, suggesting that Cx43 participates in mechanotransduction. However, mice lacking Cx43 in osteoblasts and/or osteocytes show an increased anabolic response to loading, and decreased catabolic response to unloading. This evidence suggests that Cx43 channels expressed in osteoblastic cells are not required for the response to mechanical stimulation, but mediate the consequence. The molecular basis of these unexpected responses to mechanical stimulation is currently under investigation.

Direct Melanoma Cell Contact Induces Stromal Cell Autocrine Prostaglandin E2-EP4 Receptor Signaling That Drives Tumor Growth, Angiogenesis, and Metastasis

“…On the other hand, epidermal host cells expressed Cx26, and the expression of Cx26 in the adjacent non-cancer tissues may be useful to identify patients with a high risk of metastasis. Cx43 is expressed in osteoblasts as gap junction channels (32), and B16 cells express Cx26 (31). Further studies are needed to define a cell surface molecule involved in cell-cell interaction between B16 melanoma and osteoblasts.…”

High-resolution 3D imaging of osteocytes and computational modelling in mechanobiology: insights on bone development, ageing, health and disease

“…However, other evidence suggests that inhibiting this communication can enhance bone formation during loading High-resolution 3D imaging of osteocyte anatomy and pathology and preserve it during unloading, which is reviewed by Lloyd and colleagues (2014). Recent studies have shown that the osteocyte gap junction channel Connexin 43 plays an integral role in bone mechanobiology and osteocyte viability (Plotkin et al, 2015;Riquelme et al, 2015;Xu et al, 2015). Primary cilia.…”

“…Recent studies have shown that the osteocyte gap junction channel Connexin 43 plays an integral role in bone mechanobiology and osteocyte viability (Plotkin et al, 2015;Riquelme et al, 2015;Xu et al, 2015). Primary cilia.…”

Connexins and pannexins in the skeleton: gap junctions, hemichannels and more

“…In vitro studies showed that Cx43 expression is required for the response of osteoblastic and osteocytic cells to mechanical stimulation [120]. Based on this finding, it was hypothesized that the response to mechanical loading is eliminated, or at least reduced, in the absence of Cx43 in osteoblasts and/or osteocytes.…”

“…This primes osteoblastic cells to respond to mechanical signals by a yet to be identified mechanism. However, the detailed molecular pathway that mediates this inhibitory effect of Cx43 on bone formation induced by mechanical forces remains to be determined [120]. …”