Experimental osteoarthritis induced by surgical realignment of the patella in BALB/c mice

Abstract

The patellofemoral joint is an important source of symptoms in osteoarthritis of the knee. We have used a newly designed surgical model of patellar strengthening to induce osteoarthritis in BALB/c mice and to establish markers by investigating the relationship between osteoarthritis and synovial levels of matrix metalloproteinases (MMPs). Osteoarthritis was induced by using this microsurgical technique under direct vision without involving the cavity of the knee. Degeneration of cartilage was assessed by the Mankin score and synovial tissue was used to determine the mRNA expression levels of MMPs. Irrigation fluid from the knee was used to measure the concentrations of MMP-3 and MMP-9. Analysis of cartilage degeneration was correlated with the levels of expression of MMP. After operation the patellofemoral joint showed evidence of mild osteoarthritis at eight weeks and further degenerative changes by 12 weeks. The level of synovial MMP-9 mRNA correlated with the Mankin score at eight weeks, but not at 12 weeks. The levels of MMP-2, MMP-3 and MMP-14 mRNA correlated with the Mankin score at 12 weeks. An increase in MMP-3 was observed from four weeks up to 16 weeks. MMP-9 was notably increased at eight weeks, but the concentration at 16 weeks had decreased to the level observed at four weeks. Our observations suggest that MMP-2, MMP-3 and MMP-14 could be used as markers of the progression of osteoarthritic change.

Transcriptional profiling of murine macrophages stimulated with cartilage fragments revealed a strategy for treatment of progressive osteoarthritis

“…Another positive regulator of inflammatory response found in the gene profile was Aif1, which is known to be highly expressed in synovial tissues of rheumatoid arthritis patients 32 . In addition, macrophages in response to cartilage fragments stimulation expressed proteolytic enzymes including matrix metalloproteinases Mmp9 and Mmp14, and disintegrin and metalloproteinase domain-containing protein 17 (Adam17), which are known to be involved in demineralization of bone, degradation of components of the extracellular matrix and digestion of matrix proteins [33][34][35][36] . Not surprisingly, our bioinformatic analysis revealed that the upregulated genes in stimulated macrophages were significantly enriched in rheumatoid arthritis.…”

Induction of osteoarthritis by injecting monosodium iodoacetate into the patellofemoral joint of an experimental rat model

“…Egloff et al investigated the effect of muscle weakness using surgical denervation and intramuscular drug injection on the progression of OA, and exhibited an increase in the OARSI score of the PF joint at 3 months postoperatively [ 34 ]. Chia et al used a newly designed surgical model to induce OA in mice and stated that the PF joint showed evidence of mild OA at 8 weeks and further degeneration at 12 weeks after surgery [ 35 ]. Though these studies were able to report these changes in PFOA, the studies reported findings that had problems with temporal, not sequential, histopathological evaluation and the reproduction of only mild OA or OA during the early stage.…”

Review of Soluble Biomarkers of Osteoarthritis: Lessons From Animal Models

“…8 COMP, MMP-3, and MMP-9 synovial fluid levels also increased in mice after acute joint injury induced by intraarticular fracture. 38,39 In a study of Porta et al, 40 the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) did not modify serum levels of MIA and control groups.…”