Cyclic Strain Stimulates Proliferative Capacity, 2 Integrin by Human Articular Chondrocytes from Osteoarthritic Knee Joints

Articular cartilage, the load-bearing tissue in diarthrodial joints, is continually subjected to mechanical stimulation. Cartilage tissue consists of an extracellular matrix (ECM) and is sparsely populated by chondrocytes. Although chondrocytes comprise less than 10% of cartilage, these cells sense and respond to the mechanical stimuli. However, the effects of mechanical signals at the cellular level are still not fully defined. Moreover, the mechanisms by which chondrocytes respond to mechanical signals are not fully understood. The purpose of this study was to test the hypothesis that mechanical stimulation in the form of cyclic strain modulates proliferative capacity and integrin expression of chondrocytes from osteoarthritic knee joints. We also examined the effect of mechanical stimulation on integrin expression since it has been proposed to mediate the transduction of mechanical signals. Chondrocytes were isolated from human knees during total knee arthroplasty and were propagated in microcarrier spinner culture for 2 weeks. Cells were subsequently harvested and then plated onto flexible-bottom wells. They were then subjected to cyclic strain for 24 hr using a computer-controlled vacuum device, while replicate samples were maintained under static conditions. Proliferative capacity was determined by radiolabeled thymidine uptake. Phenotype and integrin expression were analyzed by reversetranscriptase polymerase chain reaction (RT-PCR). Cyclic strain increased proliferative capacity by about 30% of controls. RT-PCR analysis of mRNA expression showed that cyclic strain enhanced expression of collagen type II and aggrecan whereas Col I expression was unaltered. Parallel to enhancement of the chondrocytic phenotype, the expression of integrin 2 subunit was also enhanced. In contrast, there was a slight but noticeable change in 5 integrin expression and no change in the 1 integrin. These results demonstrate that mechanical stimulation by cyclic strain can directly alter proliferative capacity, phenotype expression, and integrin 2 subunit expression by human chondrocytes. Our observations agree with previous findings for the behavior of chondrocytes subjected to a mechanical stress and also support the theory that integrins may participate in mediating the response of chondrocytes to their mechanical environment.