Abstract
Osteoarthritis (OA) pain is often associated with expression of tumor necrosis factor (TNF-α), suggesting that TNF-α is one of the main contributing factors that causes inflammation, pain and OA pathology. Thus, inhibition of TNF-α could potentially improve OA symptoms and slow disease progression. Anti-TNF-α treatments with antibodies, however, require multiple treatments and cannot entirely block TNF-α. Tumor necrosis factor α-induced protein 8-like 2 (TIPE2) was found to regulate the immune system’s homeostasis, and inflammation, through different mechanisms from anti-TNF-α therapies. With a single treatment of AAV-TIPE2 gene delivery in the accelerated aging Z24-/- mouse model, we found differences in Safranin O staining intensity within the AC region of knee between TIPE2 treated mice and control mice. The glycosaminoglycan content (orange-red) was degraded in the Z24-/- cartilage while shown to be restored in the TIPE2 treated Z24-/- cartilage. We also observed that chondrocytes in Z24-/- mice exhibited a variety of senescent-associated phenotypes. Treatment with TIPE2 decreased TNF-α positive cells, β-Gal activity and p16 expression seen in Z24 -/- mice. Our study demonstrated that AAV-TIPE2 gene delivery effectively blocked TNF-α induced inflammation and senescence and result resulting in the prevention or delay of knee OA in our accelerated aging Z24-/- mouse model.
Published Version
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