Osteoarthritis (OA) pain is often associated with the expression of tumor necrosis factor alpha (TNF-α), suggesting that TNF-α is one of the main contributing factors that cause 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. TNF-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 adeno-associated virus (AAV)-TIPE2 gene delivery in the accelerated aging () mouse model, we found differences in Safranin O staining intensity within the articular cartilage (AC) region of the knee between TIPE2-treated mice and control mice. The glycosaminoglycan content (orange-red) was degraded in the cartilage while shown to be restored in the TIPE2-treated cartilage. We also observed that chondrocytes in mice exhibited a variety of senescent-associated phenotypes. Treatment with TIPE2 decreased TNF-α-positive cells, β-galactosidase (β-gal) activity, and p16 expression seen in mice. Our study demonstrated that AAV-TIPE2 gene delivery effectively blocked TNF-α-induced inflammation and senescence, resulting in the prevention or delay of knee OA in our accelerated aging mouse model.

中文翻译：

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TIPE2基因转移通过减少炎症和细胞衰老来改善早衰小鼠模型中与衰老相关的骨关节炎


骨关节炎 (OA) 疼痛通常与肿瘤坏死因子 α (TNF-α) 的表达相关，这表明 TNF-α 是引起炎症、疼痛和 OA 病理的主要影响因素之一。因此，抑制 TNF-α 可能会改善 OA 症状并减缓疾病进展。然而，用抗体进行抗 TNF-α 治疗需要多次治疗，并且不能完全阻断 TNF-α。研究发现 TNF-α 诱导蛋白 8-like 2 (TIPE2) 可通过与抗 TNF-α 疗法不同的机制来调节免疫系统的稳态和炎症。通过在加速衰老小鼠模型中进行腺相关病毒 (AAV)-TIPE2 基因递送的单次治疗，我们发现经过 TIPE2 治疗的小鼠和经过 TIPE2 治疗的小鼠膝关节软骨 (AC) 区域内番红 O 染色强度存在差异。控制老鼠。糖胺聚糖含量（橙红色）在软骨中被降解，而在 TIPE2 处理的软骨中则被恢复。我们还观察到小鼠的软骨细胞表现出多种与衰老相关的表型。 TIPE2 治疗降低了小鼠中的 TNF-α 阳性细胞、β-半乳糖苷酶 (β-gal) 活性和 p16 表达。我们的研究表明，AAV-TIPE2 基因传递可有效阻止 TNF-α 诱导的炎症和衰老，从而在我们的加速衰老小鼠模型中预防或延迟膝关节 OA。