Molecular response to cartilage injury

Background

Post-traumatic osteoarthritis (OA) represents 13% of all OA of the knee, 9% in the hip, and 73% of all OA of the ankle [1]. The molecular mechanisms that underlie the development of chronic joint surface degeneration following a localised, acute joint injury are not known. The aim of this study is to utilise the cartilage explant model system to identify molecular mechanism of cartilage damage and repair induced by acute mechanical injury.

Methods

Explants of articular cartilage from preserved areas of the femoral condyles or the patellar groove of patients undergoing total knee prosthesis were cultured in vitro under different conditions. After 4 days in culture the samples were subjected or not to mechanical injury by performing full thickness cuts at a distance of 1 mm. At different time-points the explants were partly snap-frozen for further histochemical/immunohistochemical evaluation and partly used for RNA extraction and RT-PCR analysis. The original cartilage was graded using the Mankin score.

Results

Gene regulation was detected as early as 4 hours and lasting for at least 6 days after mechanical injury. BAX mRNA, possibly associated with apoptosis of chondrocytes, MMP-8, and TIMP-1 mRNA were upregulated in the injured explants. BMP-2 mRNA was also upregulated by mechanical injury. We could not detect changes upon damage of cell proliferation as measured by PCNA mRNA levels at the analysed time points.

Conclusions

The explant model system represents a controlled experimental setup to study the molecular mechanisms of cartilage degeneration in post-traumatic OA and to identify potential molecular targets for its prevention.