*2.2. The IA Administration of 7 rh Improves the Weight Distribution Ability and Running Endurance after OA-Induction*

The weight distribution test and running endurance assessment were used to evaluate the functional performance of knee joints after OA induction with or without 7 rh treatment. During the treatment course, we did not observe an apparent change in weight-bearing ability of the studied limb in both of the sham control groups (sham+ saline and sham+ 7 rh 13.8 nM), but a significantly reduced ability to bear weight in ACLT mice (*p* < 0.001 compared with the sham control groups). In contrast, the mice in 7 rh-treated groups could bear approximately 50% of their body weight since the third week, and the effects persisted to the residual treatment course (Figure 2A).

**Figure 2.** Treatment with 7 rh promoted knee function after anterior cruciate ligament transection (ACLT). (**A**) Weight-bearing test. There were no obvious influences in both of the sham control groups (sham+ saline and sham+ 7 rh 13.8 nM) during the treating courses. The weight-bearing ability of the studied limb was significantly reduced after osteoarthritis (OA) induction (*p* < 0.001). Mice in the OA + 7 rh group could bear significantly more weight since the third week (*p* < 0.001 at both concentrations) and thereafter until the end of the study (all *p* < 0.001). (**B**) Treadmill running test. The mice in the ACLT-OA group could endure less time in gait occurred than those in the sham control groups (*p* < 0.001) at 5 weeks. In both treating groups, the mice significantly increased their running endurance in the treadmill test (all *p* < 0.001) with no significant difference from mice in the sham control groups. (\*\*\* *p* < 0.001 versus the sham control groups; ### *p* < 0.001 versus the ACLT group).

The running endurance is an indicator of knee function improvement. As the results of the weight distribution test, the running endurance was significantly reduced after OA induction. The mice in both sham control groups could finish the 15 min running test, whereas the mice in the ACLT group could only endure 4.5 ± 0.8 min at 5 weeks. Notably, 7 rh significantly increased the mice' endurance levels to 12.5 ± 0.8 min in 6.9 nM 7 rh group and 13.5 ± 0.8 min in the 13.8 nM 7 rh group, respectively, at 5 weeks, which is not a significant difference compared to the sham control groups (Figure 2B).
