Characterization of spontaneous facet joint osteoarthritis

Abstract

Purpose: Although rodent models of traumatically or chemically induced spinal facet joint osteoarthritis (FJOA) were previously described, animal models of typical spontaneous FJOA haven’t been documented. This study aimed to identify the characteristics of murine spontaneous FJOA and its molecular mechanisms. Methods: The lumbar facet joints of mice bearing mutant NFAT1 alleles and of wild-type (WT, control) mice were examined by histopathology, quantitative gene expression, immunohistochemistry, and histomorphometry using a novel FJOA scoring system at 2, 6, 12, and 18 months of age. The reproducibility of the FJOA scoring system was confirmed by inter-observer and intra-observer variability tests. Tissue-specific histomorphometric and gene expression changes were statistically analyzed. Results: NFAT1-mutant facet joints displayed dysfunction of articular chondrocytes and synovial cells with aberrant gene and protein expression in cartilage and synovium as early as 2 months. osteoarthritic structural changes such as articular surface destruction and chondro-osteophyte formation became evident in NFAT1-mutant facet joints at 6 months. Severe FJOA changes including deeper cartilage loss, synovial thickening, separation of cartilage from thickened subchondral bone, as well as tissue-specific molecular and cellular alterations were evident in NFAT1-mutant mice at 12 and 18 months. OA-like structural changes were not detected in WT facet joints at any ages, though aging-related cartilage degeneration was observed at 18 months. Conclusions: This study characterized a novel murine model of spontaneous FJOA and developed the first FJOA scoring system. The age- and tissue-specific molecular and cellular characteristics in the NFAT1-mutant facet joints have provided new insights into the pathogenetic mechanisms for initiation and progression of spontaneous FJOA.