In contrast, rapamycin kinase inhibitor Bosutinib treated mice showed a focal loss of proteoglycan staining without severe articular cartilage loss at 8 weeks and lesions with a loss of proteoglycan staining slightly increased 12 weeks after surgery. however, hyaline cartilage was Inhibitors,Modulators,Libraries preserved. The extent of OA was evaluated by scoring specific parameters of OA, and is presented as summed scores. Using the summed OA score, DMSO treated mice developed OA in a time dependent manner and had a significantly higher score than the rapamycin treated mice at 8 and 12 weeks following DMM surgery. The summed OA score in the rapamycin treated Inhibitors,Modulators,Libraries mice at 12 weeks was increased compared to the score at 8 weeks. These results suggested that the intra articular injection of rapamycin did not completely prevent but delayed articular cartilage degradation in the presence of meniscus injury after DMM surgery.

The local intra articular injection of rapamycin decreased p mTOR and increased LC3 expression To determine whether the local intra articular injection of rapamycin modulates mTOR and autophagy, the effects that rapamycin had on phospho mTOR and LC3 expressions were examined. The expression of p mTOR was increased in DMSO treated mice Inhibitors,Modulators,Libraries at 8 and 12 weeks post DMM surgery compared to DMSO treated Inhibitors,Modulators,Libraries mice undergoing the sham knee operation. Rapamycin treatment suppressed p mTOR expression in these mice compared to those treated with DMSO at both the 8 and 12 week time points post DMM injury. The expression of p mTOR in the rapamycin treated mice was significantly increased at 12 weeks compared to 8 weeks after DMM injury.

In contrast, LC3 positive cells were higher in the articular cartilage maintaining proteoglycan staining but lower in the degenerated articular cartilage of the DMSO treated mice after DMM surgery. An increased in LC3 positive cells was observed in the rapamycin treated mice compared to those treated with DMSO at 8 and 12 weeks post DMM surgery. The number of LC3 positive Inhibitors,Modulators,Libraries cells in the rapamycin treated mice decreased significantly at 12 weeks compared to 8 weeks post DMM injury. Figure 2 The effect of rapamycin on p mTOR and LC3 expressions. Representative images of immunostaining for p mTOR and LC3. Scale bar 20 um. Quantification of p mTOR positive cell was calculated. Rapamycin treatment suppressed p mTOR expression in the rapamycin treated mice compared to those treated with DMSO Volasertib cost at both the 8 and 12 week time points. Quantification of LC3 positive cells was calculated.