Reduced PDGF-AA in subchondral bone leads to articular cartilage degeneration after strenuous running.

To identify the effects of running on articular cartilage and subchondral bone remodeling, C57BL/6 mice were randomly divided into three groups: control, moderate-, and strenuous running. Magnetic resonance imaging showed bone marrow lesions in the knee subchondral bone in the strenuous-running group in contrast with the other two groups. The microcomputed tomography analysis showed promoted bone formation in the subchondral bone in mice subjected to strenuous running. Histological and immunohistochemistry results indicated that terminal differentiation of chondrocytes and degeneration of articular cartilage were enhanced but, synthesis of platelet-derived growth factor-AA (PDGF-AA) in the subchondral bone was suppressed after strenuous running. In vitro, excessive mechanical treatments suppressed the expression of PDGF-AA in osteoblasts, and the condition medium from mechanical-treated osteoblasts stimulated maturation and terminal differentiation of chondrocytes. These results indicate that strenuous running suppresses the synthesis of PDGF-AA in subchondral bone, leading to downregulated PDGF/Akt signal in articular cartilage and thus cartilage degeneration.