Evidence for articular cartilage regeneration in MRL/MpJ mice

Objective: A major clinical problem in Orthopaedics is the repair of traumatic articular cartilage lesions. The MRL/MpJ strain of mice has the remarkable ability to regenerate ear hole punch wounds seamlessly including the scarless replacement of multiple tissues. The objective of this study was to assess whether articular cartilage defects repair or regenerate in the MRL/MpJ 'healer' strain of mice. Method: Full thickness and partial thickness lesions were introduced into trochlear groove articular cartilage of MRL/MpJ and C57Bl/6 mice, a control strain that does not undergo ear hole regeneration. The wound sites were assessed 6 weeks and 12 weeks post-surgery using a histological scoring scheme and immunohistochemistry for markers of articular cartilage including proteoglycan, collagen II and collagen VI. Results: The partial thickness lesions did not repair in either strain. However, at both 6 weeks and 12 weeks timepoints the MRL/MpJ mice had a superior healing response of full thickness lesions with abundant chondrocytes and an extracellular matrix rich in proteoglycan, collagen II and collagen VI at the wound site. At the 12 week timepoint the enhanced cartilage healing was restricted to male MRL/MpJ mice. In contrast, the C57Bl/6 control strain produced an extracellular matrix at the wound site that, overall, had significantly less matrix proteoglycan and collagen II. Conclusions: Male MRL/MpJ mice appear to possess an intrinsic ability to 'regenerate' articular cartilage. Understanding the biochemical and genetic basis for articular cartilage regeneration may open up new treatment options for traumatic articular cartilage defects.