Axial strain enhances osteotomy repair with a concomitant increase in connexin43 expression
Rishi R Gupta , Hyunchul Kim , Yu-Kwan Chan , Carla Hebert , Leah Gitajn , David J Yoo , Robert V O'Toole , Adam H Hsieh , Joseph P Stains
Bone Research ›› 2015, Vol. 3 ›› Issue (1) : 15007
Axial strain enhances osteotomy repair with a concomitant increase in connexin43 expression
The mechanical environment is known to influence fracture healing. We speculated that connexin43 (Cx43) gap junctions, which impact skeletal homeostasis, fracture healing and the osteogenic response to mechanical load, may play a role in mediating the response of the healing bone to mechanical strain. Here, we used an established rat fracture model, which uses a 2 mm osteotomy gap stabilized by an external fixator, to examine the impact of various cyclical axial loading protocols (2%, 10%, and 30% strain) on osteotomy healing. We examined the presence of Cx43 in the osteotomy-healing environment and assessed how mechanical strain modulates Cx43 expression patterns in the callus. We demonstrated that increased cyclical axial strain results in increased radiographic and histologic bone formation. In addition, we show by immunohistochemistry that Cx43 is abundantly expressed in the healing callus, with the expression most robust in samples exposed to increased cyclical axial strain. These data are consistent with the concept that an increase in Cx43 expression by mechanical load may be part of the mechanisms by which mechanical forces enhances fracture healing.
Bone fractures: Why movement aids healing
Low-level mechanical strain on bone fractures enhances the expression of a protein which triggers new bone formation and accelerates healing. The protein connexin43 (Cx43) aids intercellular communication in bone, and is abundantly expressed in both newly forming and mature bones. Scientists have long understood that some degree of movement and mechanical strain can aid the healing of fractures, but the precise reasons were unclear. Joseph Stains and co-workers at the University of Maryland, USA, conducted a series of experiments on rats to examine Cx43 expression in response to low-level mechanical strain. The team found that incremental mechanical loading of up to 30% strain on fractured bone led to a corresponding increase in Cx43 expression. The increased protein levels directly influenced bone formation around the fractures, leading to quicker, more effective healing.
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