Gap junctions and hemichannels in signal transmission, function and development of bone

Abstract

Gap junctional intercellular communication (GJIC) mediated by connexins, in particular connexin 43 (Cx43), plays important roles in regulating signal transmission among different bone cells and thereby regulates development, differentiation, modeling and remodeling of the bone. GJIC regulates osteoblast formation, differentiation, survival and apoptosis. Osteoclast formation and resorptive ability are also reported to be modulated by GJIC. Furthermore, osteocytes utilize GJIC to coordinate bone remodeling in response to anabolic factors and mechanical loading. Apart from gap junctions, connexins also form hemichannels, which are localized on the cell surface and function independently of the gap junction channels. Both these channels mediate the transfer of molecules smaller than 1.2 kDa including small ions, metabolites, ATP, prostaglandin and IP3. The biological importance of the communication mediated by connexin-forming channels in bone development is revealed by the low bone mass and osteoblast dysfunction in the Cx43-null mice and the skeletal malformations observed in occulodentodigital dysplasia (ODDD) caused by mutations in the Cx43 gene. The current review summarizes the role of gap junctions and hemichannels in regulating signaling, function and development of bone cells.

Lycopene Intake Facilitates the Increase of Bone Mineral Density in Growing Female Rats

“…The intracellular gap junctional communication among osteocytes, osteoblasts, and osteoclasts plays crucial roles in bone remodeling (38). Previous cellular studies have shown that lycopene inhibited osteoclast differentiation and activation, and facilitated osteoblast differentiation and proliferation (17,18).…”

Fluid Flow-Induced Calcium Response in Osteoclasts: Signaling Pathways

“…37 Osteoclast formation and resorptive ability are also reported to be modulated by gap junction. 2,16,28 But it still remains unknown whether this connexin-dependent behaviors of osteoclasts are involved with calcium response.…”

Connexin 43 Modulates Osteogenic Differentiation of Bone Marrow Stromal Cells Through GSK-3beta/Beta-Catenin Signaling Pathways

“…Cx43, encoded by the Gja1 gene, is the most ubiquitous gap junction protein expressed in bone cell types, including chondrocytes, osteoblasts, osteocytes, osteoclasts, and BMSCs [14, 16]. Cx43 plays important roles in regulating signal transmission among different bone cell types and thereby regulates development, differentiation, modeling and remodeling, as well as pathologies of bone [16-19].…”