Fig 2: XMU-MP-1 alleviates articular cartilage degeneration during OA process. (A) Representative images of HE staining of knee joint sections from mice of indicated groups. SHAM: Mice underwent sham surgery. Vehicle: Mice undergoing DMM surgery were intraperitoneally injected with vehicle. XMU-MP-1: Mice undergoing DMM surgery were intraperitoneally injected with XMU-MP-1. Panels in the middle are high magnifications of boxed regions in the left panels; panels on the right are high magnifications of boxed regions in the middle panels. (B) Representative images of Safranin O/Fast Green staining of knee joint sections from mice of indicated groups. SHAM: Mice underwent sham surgery. Vehicle: Mice undergoing DMM surgery were intraperitoneally injected with vehicle. XMU-MP-1: Mice undergoing DMM surgery were intraperitoneally injected with XMU-MP-1. Panels in the middle are the high magnification of the solid box-like area in the left panels, panels on the right are the high magnification of the dotted box-like area in the left panels. (C) Statistical analysis of OARSI scores in B. n = 8, 12, 14. (D) Statistical analysis of thickness of hyaline cartilage (HC), calcified cartilage (CC), and ratio of HC to the CC in A. n = 8, 12, 14. All data are presented as mean ± SEM. ns p > 0.05, *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

Fig 3: XMU-MP-1 attenuates articular cartilage degradation during OA pathogenesis. (A) Representative images of knee joint sections of mice from indicated groups. SHAM: Mice underwent sham surgery. Vehicle: Mice undergoing DMM surgery were intraperitoneally injected with vehicle. XMU-MP-1: Mice undergoing DMM surgery were intraperitoneally injected with XMU-MP-1. Sections were immunostained with antibody against COL? (red or gray). Panels on the right are high magnifications of boxed regions in the left panels. The white dashed lines marked the edge of cartilage. The yellow dashed lines marked the tidemark. (B) Statistical analysis of the relative fluorescence of COL? in hyaline cartilages in A. n = 3, 6, 5. (C) Representative images of knee joint sections of mice from indicated groups. SHAM: Mice underwent sham surgery. Vehicle: Mice undergoing DMM surgery were intraperitoneally injected with vehicle. XMU-MP-1: Mice undergoing DMM surgery were intraperitoneally injected with XMU-MP-1. Sections were immunostained with antibody against MMP13 (red or gray). Panels on the right are high magnifications of boxed regions in the left panels. The dashed lines marked the edge of cartilage. The yellow arrows mark the MMP13+ chondrocytes in calcified cartilage. (D) Statistical analysis of the MMP13+ chondrocytes numbers in articular cartilage in C. Panel on the left is quantification of MMP13+ chondrocytes numbers per cartilage. Panel on the right is the quantification of relative fluorescence in MMP13+ chondrocytes. n = 3, 6, 6. All data are presented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

Fig 4: Effects of statin treatment on collagen type II expression after cartilage trauma. Expression of COL2 was determined by means of (A) gene expression analysis of COL2A1 as well as (B) quantification of CPII release. Significant differences between groups were depicted as [versus T] * = p < 0.05 [versus C] c = p < 0.05, cc = p < 0.01; n = 5. Blank box = unimpacted control (C), shaded boxes = traumatized cartilage explants (T).

Fig 5: XMU-MP-1 attenuates OA pathogenesis via YAP. Representative images of knee joint sections of mice from indicated groups. SHAM: Mice underwent sham surgery. Vehicle: Mice undergoing DMM surgery were intraperitoneally injected with vehicle. XMU-MP-1: Mice undergoing DMM surgery were intraperitoneally injected with XMU-MP-1. Sections were immunostained with antibody against YAP (red or gray) (A) and MST1 (red or gray) (C). (B) Statistical analysis of the YAP+ chondrocytes numbers in articular cartilage in A. Panel on the left is quantification of YAP+ chondrocytes numbers per cartilage. Panel on the right is the quantification of relative fluorescence in YAP+ chondrocytes. n = 4, 3, 4. (D) Statistical analysis of the MST1+ chondrocytes numbers in articular cartilage in C. Panel on the left is quantification of MST1+ chondrocytes numbers per cartilage. Panel on the right is the quantification of relative fluorescence in MST1+ chondrocytes. n = 5, 5, 3. All data are presented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.