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

Biochim Biophys Acta. 2012 Aug;1818(8):1909-18. doi: 10.1016/j.bbamem.2011.09.018. Epub 2011 Sep 22.

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 1.2kDa including small ions, metabolites, ATP, prostaglandin and IP(3). 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. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis
  • Bone Marrow Cells / cytology
  • Bone Remodeling
  • Bone and Bones / metabolism*
  • Cell Communication
  • Cell Differentiation
  • Cell Proliferation
  • Chondrocytes / cytology
  • Connexin 43 / metabolism
  • Craniofacial Abnormalities / metabolism
  • Eye Abnormalities / metabolism
  • Foot Deformities, Congenital / metabolism
  • Gap Junctions / physiology*
  • Humans
  • Models, Biological
  • Osteoblasts / cytology
  • Osteoblasts / metabolism
  • Osteoclasts / cytology
  • Osteocytes / cytology
  • Osteocytes / metabolism
  • Signal Transduction
  • Stromal Cells / cytology
  • Syndactyly / metabolism
  • Tooth Abnormalities / metabolism

Substances

  • Connexin 43

Supplementary concepts

  • Oculodentodigital Dysplasia