Objective Recent studies have implicated the cyclin dependent kinase inhibitor, p21, in enhanced tissue regeneration observed in MRL/MpJ “super-healer” mice. Specifically, p21 is downregulated in MRL cells and similar ear hole closure to MRL mice has been observed in p21−/− mice. However, the direct implications of p21 deletion in endogenous articular cartilage regeneration remain unknown. In this study, we investigated the role of p21 deletion in the ability of mice to heal full-thickness cartilage defects (FTCDs). Design C57BL/6 and p21−/− ( Cdkn1atm1Tyj) mice were subjected to FTCD and assessment of cartilage healing was performed at 1 hour, 3 days, 1 week, 2 weeks, and 4 weeks post-FTCD using a 14-point histological scoring system. X-ray microscopy was used to quantify cartilage healing parameters (e.g., cartilage thickness, surface area/volume) between C57BL/6 and p21−/− mice. Results Absence of p21 resulted in increased spontaneous articular cartilage regeneration by 3 days post-FTCD. Furthermore, p21−/− mice presented with increased cartilage thickness at 1 and 2 weeks post-FTCD compared with uninjured controls, returning to baseline by 4 weeks post-FTCD. Conclusions We report that p21−/− mice display enhanced articular cartilage regeneration post-FTCD compared with C57BL/6 mice. Furthermore, cartilage thickness was increased in p21−/− mice at 1 week post-FTCD compared with uninjured p21−/− mice and C57BL/6 mice.

Sag is an intrinsic feature of healthy human adductor pollicis muscle. The length-dependence of sag is related to greater diminution of twitch force at short relative to long muscle length. The dependence of sag on IPI is related to IPI-dependent changes in twitch duration and twitch force, and the timing of peak twitch force relative to the peak force of the associated unfused tetanus.