Abstract: Objective To evaluate the effects of treadmill running exercise of different intensity on early repair of full-thickness
defects on the patellofemoral articular surface and the changes in the expressions of matrix metalloproteinase-3 (MMP-3) and
tissue inhibitor of metalloproteinase-1 (TIMP-1) in SD rats. Methods Twenty-four male SD rats with full-thickness defects on
the patellofemoral articular surface were randomly assigned into sedentary control (SED) group and low-, moderate- and
high-intensity running groups (LIR, MIR, and HIR groups, respectively). The running groups were trained on treadmill for 6
consecutive weeks. Blood samples were collected to detect serum MMP-3 and TIMP-1 levels using ELISA before and after the
experiment, and the femoral trochleas were collected to assess tissue repair by gross appearance scoring and O’Driscoll
histological scoring with Safranine O-Fast Green staining and Toluidine blue staining. Results In rats in SED group, the defect
was filled with hyaline articular cartilage-like tissues, as compared to fibrous tissues in LIR and MIR groups and subchondral
bone damage in HIR group. The SED group scored the highest and HIR group the lowest among the 4 groups in gross
appearance scoring and O’Driscoll histological scoring. No significant differences were found in MMP-3 or TIMP-1 levels
among the groups before training (P>0.05), but after 6 weeks of training, serum MMP-3 and TIMP-1 levels differed
significantly among the 4 groups (P<0.05), and all the 3 running groups had a significantly higher MMP-3 level than the
control group (P<0.05). After the 6-week training, TIMP-1/MMP-3 ratio was significantly higher in SED group than in the 3
running groups, and was the lowest in HIR group. Conclusion Both low- and moderate-intensity exercise failed to promote
resurfacing of full-thickness cartilage defects on the patellofemoral articular surface in rats, and high-intensity exercise even
induces subchondral bone damage. The expression of MMP-3 and TIMP-1 is related to exercise, and the TIMP-1/MMP-3 ratio
reflects the extent of tissue repair.