PROLIFERATIVE AND PHENOTYPIC RESPONSES OF BONE-LIKE CELLS TO MECHANICAL DEFORMATION

Limited in vivo and in vitro experiments suggest that bone and bone-li ke cells respond to mechanical signals in a trigger-like rather than a dose-response fashion: i.e., they fail to respond until they have bee n stimulated with some given number of cycles of loading, and then onc e they respond, additional cycles produce little or no effect. To expl ore this notion, rat calvaria-derived osteoblast-like cells and the ce ll line MC3T3-E1 were plated at a high cell density (5,000 cells/mm(2) ) on silicone membranes coated with type-I collagen and were allowed t o attach for 24 hours. The membranes then were exposed to vacuum press ure (-1 kPa, 0.5 Hz) on a daily basis, and cultures were assayed every 2 days for 2 weeks. The proliferation of nontransformed cells increas ed 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 r esponse than four cycles per day. We observed inverse phenotypic respo nses: the expression of osteocalcin was depressed compared with contro ls in the cultures of osteoblast-like cells that were strained with as few as four cycles per day. Alkaline phosphatase activity was depress ed 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 v acuum application. Bone-like cells in vitro appear to exhibit trigger- response behavior analogous to that seen in bone in vivo; the phenotyp ic response occurs in the opposite direction from the proliferative re sponse.