Abstract
Despites the fact that T cells are involved in the pathogenesis of osteoarthritis (OA) little is known about the roles of CD8+ T cells in this disease. We investigated the effects of CD8+ T cells and the expression of tissue inhibitor of metalloproteinases 1 (TIMP-1) on joint pathology. Using anterior cruciate ligament-transection (ACLT), OA was induced in mice. The knee joints were histologically assessed for manifestations of OA. The CD8+ T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. Local expression of TIMP-1, matrix metalloproteinase (MMP)-13, and VEGF were examined. Cartilage degeneration was slower in CD8+ T cell knockout mice than in control mice. CD8+ T cells were activated once OA was initiated and expanded during OA progression. More CD8+ T cells from splenocytes expressed TIMP-1 in ACLT-group mice than in Sham-group mice. The number of TIMP-1-expressing CD8+ T cells in OA mice correlated with the disease severity. TIMP-1 expression in cartilage was co-localized with that of MMP-13 and VEGF. TIMP-1 protein was detected in synovium in which angiogenesis occurred. During the pathogenesis of OA, the expression of TIMP-1, VEGF and MMP-13 accompanying with CD8+ T cells activation were increased. Furthermore, inhibiting the expression of TIMP-1 in joints could retard the progression of OA.
Highlights
Osteoarthritis (OA), a chronic and progressive disorder of the joints, is one of the most prevalent diseases in humans
The knee cartilage and synovial specimens were removed on day 30, 60, and 90. 30 days after surgery, the irregularity on the superficial layer of cartilage and the proliferation of the lining cells in the synovium was observed in anterior cruciate ligament-transection (ACLT) group mice (Figure 1a,c)
We showed that the number of tissue inhibitor of metalloproteinases 1 (TIMP-1)-expressing CD8+ T cells in spleens was increased with the disease progression of OA (Figure 5a)
Summary
Osteoarthritis (OA), a chronic and progressive disorder of the joints, is one of the most prevalent diseases in humans. OA may be best thought of as a group of disorders with varied etiologies whose final common clinical phenotypes converge to create the complex pathophysiology of this disease. Abnormal forces acting on normal cartilage or normal forces acting on abnormal cartilage may cause structural changes in joints: osteophyte formation, synovial inflammation, and cartilage loss. By stimulating ossification in the articular cartilage and by transporting monocytes and macrophages in the synovium, angiogenesis promotes osteophyte formation and synovial inflammation [2,3]. The efficacy of treatment depends on the severity of the factors involved in the exacerbation of the disease
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