title: Gap junctions and biophysical regulation of bone cell differentiation.
abstract: Physical signals, in particular mechanical loading, are clearly important regulators of bone turnover. Indeed, the structural success of the skeleton is due in large part to the bone's capacity to recognize some aspect of its functional environment as a stimulus for achievement and retention of a structurally adequate morphology. However, while the skeleton's ability to respond to its mechanical environment is widely accepted, identification of a reasonable mechanism through which a mechanical "load" could be transformed to a signal relevant to the bone cell population has been elusive. In addition, the downstream response of bone cells to load-induced signals is unclear. In this work, we review evidence suggesting that gap junctional intercellular communication (GJIC) contributes to mechanotransduction in bone and, in so doing, contributes to the regulation of bone cell differentiation by biophysical signals. In this context, mechanotransduction is defined as transduction of a load-induced biophysical signal, such as fluid flow, substrate deformation, or electrokinetic effects, to a cell and ultimately throughout a cellular network. Thus, mechanotransduction would include interactions of extracellular signals with cellular membranes, generation of intracellular second messengers, and the propagation of these messengers, or signals they induce, through a cellular network. We propose that gap junctions contribute largely to the propagation of intracellular signals.
authors.affiliation: Musculoskeletal Research Laboratory, Departments of Orthopaedics & Rehabilitation and Cellular & Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033-0850, USA. hdonahue@psu.edu
authors.forename: H J
authors.initials: HJ
authors.lastname: Donahue
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000166:cytology*; D002450:Cell Communication; D002454:Cell Differentiation; D017629:Gap Junctions / Q000502:physiology*