Fig. 1: MSI2 is a potential target for osteoarthritis treatment.
From: Circular RNA-based protein replacement therapy mitigates osteoarthritis in male mice
a Schematic illustration of MSI2 function in three experimental models, including aging-induced osteoarthritis (OA) model, DMM-induced OA model, and human OA cartilage. DMM, destabilization of the medial meniscus. b Immunohistochemical staining of MSI2 was performed on paraffin sections of human cartilage from non-weight bearing areas (Control) and weight bearing areas (OA) in patients after arthroplasty. Scale bars = 500 μm. c Quantitative analysis of immunohistochemical staining of MSI2 using Image J software (Each group consists of n = 15 samples). The data are presented as the Mean with SEM. Statistical significance was determined by two-tailed unpaired t test. d Experimental design of tamoxifen (TAM) injection and DMM surgery in Msi2 CKO mice and littermate controls. e Micro-CT scanning showing calcified meniscus and extra bone in joints from Msi2 CKO mice after DMM surgery (calcified meniscus and extra bone are marked in red) (n = 7 mice per group). f Quantification of the bone volume (BV) of the calcified meniscus and extra bone in (e) (n = 7 mice per group). The data are presented as the Mean with SEM. Statistical significance was determined by Ordinary one-way ANOVA. g Representative images by SO&FG staining of paraffin sections from Msi2 CKO mice subjected to the DMM model 8 weeks later (n = 7 mice per group). Scale bars=500μm (top), 200μm (bottom). h Osteoarthritis Research Society International (OARSI) histopathological score of SO&FG staining in (g) (n = 7 mice per group). The data are presented as the Mean with SEM. Statistical significance was determined by Ordinary one-way ANOVA. i Quantification of subchondral bone plate (SBP) thickness in (g) (n = 7 mice per group). The data are presented as the Mean with SEM. Statistical significance was determined by Ordinary one-way ANOVA. j Schematic of intra-articular injection of AAV expressing MSI2 in DMM-treated mice to evaluate the therapeutic effects against OA. AAV-EGFP shown as the negative control, AAV-Msi2RBDmut shown as mutation of MSI2 RNA binding domain. k Micro-CT scanning showing calcified meniscus and extra bone in joints from DMM-treated mice after intra-articular injection of AAV-EGFP, -MSI2, -Msi2RBDmut (calcified meniscus and extra bone are marked in red) (n = 11,10,10,11 mice). l Quantification of the BV of the calcified meniscus and extra bone (n = 11,10,10,11 mice) in k. The data are presented as the Mean with SEM. Statistical significance was determined by Ordinary one-way ANOVA. m Representative images of SO&FG staining from DMM-treated mice after intra-articular injection of AAV-EGFP, -MSI2, -Msi2RBDmut (n = 10 mice per group). Scale bars=500μm (top), scale bars=200 μm (bottom). n OARSI histopathological score of SO&FG staining in (m) (n = 10 mice per group). The data are presented as the Mean with SEM. Statistical significance was determined by Ordinary one-way ANOVA. o Quantification of SBP thickness in (m) (n = 10 mice per group). The data are presented as the Mean with SEM. Statistical significance was determined by Ordinary one-way ANOVA. Figure 1a, d, j: Created in BioRender. Suo, J. (2025) https://BioRender.com/4byajfm.
