Proliferative and phenotypic responses of bone‐like cells to mechanical deformation

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Abstract
Limited in vivo and in vitro experiments suggest that bone and bone‐like cells respond to mechanical signals in a trigger‐like rather than a dose‐response fashion; i.e., they fail to respond until they have been stimulated with some given number of cycles of loading, and then once they respond, additional cycles produce little or no effect. To explore this notion, rat calvaria‐derived osteoblast‐like cells and the cell line MC3T3‐E1 were plated at a high cell density (5,000 cells/mm2) on silicone membranes coated with type‐I collagen and were allowed to attach for 24 hours. The membranes then were exposed to vacuum pressure (−1 kPa, 0.5 Hz) on a daily basis, and cultures were assayed every 2 days for 2 weeks. The proliferation of nontransformed cells increased 7‐fold with as few as four daily cycles but not with one cycle per day. Furthermore, 1,800 cycles of vacuum did not result in a greater response than four cycles per day. We observed inverse phenotypic responses: the expression of osteocalcin was depressed compared with controls in the cultures of osteoblast‐like cells that were strained with as few as four cycles per day. Alkaline phosphatase activity was depressed in the cultures of both the osteoblast‐like cells and the MC3T3‐E1 cells exposed to low vacuum pressures (−1 kPa) with four daily cycles of vacuum pressure. Increasing the vacuum magnitude did not affect the occurrence of a “trigger response” between one and four cycles of vacuum application. Bone‐like cells in vitro appear to exhibit trigger‐response behavior analogous to that seen in bone in vivo; the phenotypic response occurs in the opposite direction from the proliferative response.