The study on mechanotransduction mechanism of mandibular condylar chondrocytes

Objective: To investigate the mechanotransduction pathways of mandibular condylar chondrocytes under pressure. Methods: In vitro cultured mandibular condylar chondrocytes (MCC) from two-week-old New Zealand rabbits were incubated and a hydraulic pressure controlled cellular strain unit was developed to exert exact and adjustable static pressure to the cells. Cell proliferation and alkaline phosphatase activity were adopted to choose the standard short-period and long-period pressure condition. Further, the expressions of different signal molecules in mechanotransdution process were investigated by many methods including in situ hybridization, Coomassie brilliant blue staining, immunofluorescence, western blot analyse, immunocytochemical staining, spectrophotometric method and radioimmunology assay. Results: We got two different signal pathways in MCC under pressure.One is transmission process initiated by integrin-cytoskeleton system. The other is transduction process initiated by G protein locating in the cell membrane. Feasible pressure (90kPa 60min) could cause á5 and â1 integrin mRNA upregulated, cytoskekleton and F-actin expression strengthened and stress fibers assembled. At the same time, mechanical pressure could also stimulate the expression of G protein. Then the intracellular calcium increased and the protein kinase C was activated and translocated to the cytomembrane and nuclei. After that, the mitogen-activated protein kinases access was activated and the mechanical signal was transducted further into the nuclei, along with which the immediate early genes expressed. By the above-mentioned mechanotransduction ways, the mechanical simulation could cause extensive cytobiological effects including proliferation of mandibular condylar chondrocytes, elongation of cellular processes, increase of alkaline phosphatase activity, secretion of the nitric oxide, inhibition of PGF 1á level, increase of interlukin 4 and 6, upregulation of aggrecan mRNA level,etc. Conclusion: Feasible pressure could promote, while excessive pressure could prohibite, the growth and function of MCC, which are mediated by many signal molecules involved in transmission and tranduction process. TMJ. Supported by Nature Science Found of China (No. 30000035).