In multicellular organism, cells communicate with each other by gap junctions. The subunits of gap junction channels are proteins called connexins. Six-connexin proteins interact to form a ring-like pore structure called a hemichannel or connexon; these hemichannels dock to hemichannels on neighbouring cells, forming a gap junction’s pore, which provides a direct intercellular passage for small molecules or ion to move between cells.
Gap junction communication plays a critical role in bone cells such as osteoblast, osteocytes and osteoclast. In humans, more than twenty connexins have been identified but Cx43, Cx45, Cx40, Cx46 and Cx37 are expressed in the bone. Most of the gap junction possesses four transmembrane regions, with cytoplasmic amino and carboxyl regions.
Notably, Cx43, encoded by the Gja1 gene, is the most abundantly expressed connexin in bone, and has an important role in maintaining bone homeostasis. Multiple evidences have suggested that gap junction communication is important for cell growth and differentiation. Mutations in Cx43 that lead to abnormally regulated cell-cell communication are associated with a number of diseases.
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