The role of synovitis in osteoarthritis pathogenesis

Inflammation in joint injury and post-traumatic osteoarthritis

Immunopathogenesis of osteoarthritis

Objective

Traumatic and degenerative meniscal tears have different anatomic features and different proposed etiologies, yet both are associated with the development or progression of osteoarthritis (OA). In established OA, synovitis is associated with pain and progression, but a relationship between synovitis and symptoms in isolated meniscal disease has not been reported. Accordingly, we sought to characterize synovial pathology in patients with traumatic meniscal injuries and determine the relationships between inflammation, meniscal and cartilage pathology, and symptoms.



Methods

Thirty-three patients without evidence of OA who were undergoing arthroscopic meniscectomy for meniscal injuries were recruited. Pain and function were assessed preoperatively; meniscal and cartilage abnormalities were documented at the time of surgery. Inflammation in synovial biopsy specimens was scored, and associations between inflammation and clinical outcomes were determined. Microarray analysis of synovial tissue was performed, and gene expression patterns in patients with and those without inflammation were compared.



Results

Synovial inflammation was present in 43% of the patients and was associated with worse preoperative pain and function scores, independent of age, sex, or cartilage pathology. Microarray analysis and real-time polymerase chain reaction revealed a chemokine signature in synovial biopsy specimens with increased inflammation scores.



Conclusion

Our findings indicate that in patients with traumatic meniscal injury undergoing arthroscopic meniscectomy without radiographic evidence of OA, synovial inflammation occurs frequently and is associated with increased pain and dysfunction. Synovia with increased inflammation scores exhibit a unique chemokine signature. Chemokines may contribute to the development of synovial inflammation in patients with meniscal pathology; they also represent potential therapeutic targets for reducing inflammatory symptoms.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/art.30137

Synovial inflammation in patients undergoing arthroscopic meniscectomy: molecular characterization and relationship to symptoms.

Male, 10-week-old C57B1 10 mice received a single intraarticular injection in the knee joints with papain, iodoacetate, or collagenase. This led to osteoarthritic lesions, such as matrix depletion, chondrocyte proliferation, and osteophyte formation, in the injected knee joints within several weeks. After injection of iodoacetate and papain, the main osteoarthritic alterations were localized in the femoropatellar joint, whereas injection of collagenase led to marked osteoarthritic lesions in the femorotibial joint. The mechanism of induction of these alterations appears to differ for iodoacetate and papain on one site and collagenase on the other site. Data are presented that collagenase injection, by way of damaging ligaments and tendons, destabilizes the knee joint eventually leading to osteoarthritic alterations. In contrast, injection of papain or iodoacetate directly interferes with cartilage metabolism resulting in osteoarthritic changes.

Development of osteoarthritic lesions in mice by "metabolic" and "mechanical" alterations in the knee joints.

Biopsy specimens of the synovial membrane were obtained during arthroscopy and surgical meniscectomy from the knees of 20 patients with meniscus lesions. The aim of this study was to identify the morphological and immunological changes which appear in the synovium during the earliest phase of osteoarthrosis. Interstitial deposits of IgG and, in some cases, C3 were found not only in patients with evident arthrotic degeneration (cartilaginous lesions and synovitis), but also in patients who showed no overt arthrotic changes. Furthermore, light and electron microscopy showed an increased number of mast-cells with peculiar semilunar or piecemeal aspects of their secretory granules. These ultrastructural modifications are characteristic of slow, chronic release of mediators in response to a constant, moderate degranulatory stimulus. Our findings suggest that synovial changes may occur before the advent of cartilage degenertion and that the latter may be directly influenced by early pathological changes in the synovial membrane.

Early alteration of synovial membrane in osteoarthrosis

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Early alteration of synovial membrane in osteoarthrosis