The Role of p27Kip1 in the Regulation of Growth Plate Chondrocyte Proliferation in Mice

Abstract

p27/Kip1, a cyclin-dependent kinase inhibitor, negatively regulates proliferation of multiple cell types. The goal of this study was to assess the role of p27 in the spatial, temporal, and conditional regulation of growth plate chondrocyte proliferation. p27 mRNA expression was detected by real-time RT-PCR in all zones of the mouse growth plate at levels approximately 2-fold lower than in the surrounding bone. To determine whether this expression is physiologically important, we studied skeletal growth in 7-wk-old mice lacking a functional p27 gene. In these mice, body length was modestly increased and proliferation of proximal tibial growth plate chondrocytes was increased, but tibia length was not significantly greater than in controls. p27 ablation had no measurable effect on growth plate morphology. Treatment with dexamethasone inhibited longitudinal bone growth similarly in p27-deficient mice and controls, indicating that p27 is not required for the inhibitory effects of glucocorticoids on longitudinal growth. p27-deficient mice had increased width of the femoral diaphysis, suggesting that p27 acts normally to inhibit periosteal bone growth. In conclusion, our findings suggest that p27 has modest inhibitory effects on growth plate chondrocyte proliferation but is not required for the spatial or temporal regulation of proliferation or the conditional regulation by glucocorticoid.