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Regulation of bone cell sensitivity to mechanical stimulation

Bone tissue is sensitive to mechanical stimulation. Similar to other physiological systems, the capacity of bone cells to sense and transduce stimulus‐induced signals is temporally limited. This phenomenon is known as adaptation, accommodation, or desensitization, and involves one or more biochemical signaling systems that shut down mechanotransduction following stimulation. We have conducted a series of experiments demonstrating that recovery periods enhance the effectiveness of loading on osteogenesis. Moreover, several different time scales, ranging from seconds to hours to weeks, exist for resensitization to occur. Rats administered a daily dynamic loading protocol to the tibial diaphysis formed 67% more bone on the endocortical surface if the load cycles were spaced 14 sec apart, compared to contiguous cycles. In an experiment addressing resensitization on the order of hours, we administered groups of rats 4 discrete loading sessions per day, and found that rats given 8 hr recovery between each of the 4 bouts formed ~100% more bone than rats given 30 min recovery between bouts. Further experiments aimed at expanding the temporal spectrum of recovery period effects have revealed an effect of several wks recovery on bone formation. Rats loaded daily for 15 wks formed more bone if they were given wks 6–10 off (no loading), than if they were loaded for the entire 15 wk period. Desensitization appears to be an unavoidable consequence of mechanical stimulation, and it occurs on several time scales in bone. One potential cellular mechanism for short‐term desensitization involves desensitization of G‐protein coupled receptors (GPCR), a class of receptor intimately involved in mechanotransduction signaling.