ABSTRACT

Aim

Emerging data have demonstrated that low-grade inflammation in osteoarthritis, a long-held degenerative disease. The inflamed synovium produces various cytokines that induce cartilage destruction and joint pain. A previous study showed that teriparatide, an FDA approved anti-osteoporotic drug, may enhance cartilage repair. Our study focuses on its role in OA synovitis.

Materials and Methods

Primary mouse articular chondrocytes were used to determine the most potent cytokines involved in OA inflammation and cartilage destruction. A destabilization of the medial meniscus mouse model was established to investigate the effect of teriparatide in OA, particularly, on synovial inflammation and cartilage degradation.

Results

In vitro experiments showed that TNF-α was the most potent inducer of cartilage matrix-degrading enzymes, and that teriparatide antagonized the TNF-α of effect. Consistently, articular cartilage samples from TNF-α transgenic mice contained more MMP-13 positive chondrocytes than those from wild type mice. In addition, more type II collagen was cleaved in human OA cartilage than in normal cartilage samples.

Conclusions

Teriparatide can prevent synovitis and cartilage degradation by suppressing TNF-α mediated MMP-13 overexpression. Together with its chondroregenerative capability, teriparatide may be the first effective disease modifying osteoarthritis drug.

中文翻译：

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特立帕肽可预防 DMM 小鼠的滑膜炎症和软骨破坏

摘要

目的

新数据表明，骨关节炎是一种长期存在的退行性疾病，存在轻度炎症。发炎的滑膜会产生各种细胞因子，这些细胞因子会导致软骨破坏和关节疼痛。之前的一项研究表明，FDA 批准的抗骨质疏松药物特立帕肽可以增强软骨修复。我们的研究重点是它在 OA 滑膜炎中的作用。

材料和方法

原代小鼠关节软骨细胞用于确定参与 OA 炎症和软骨破坏的最有效细胞因子。建立了内侧半月板失稳小鼠模型，以研究特立帕肽对 OA 的影响，特别是对滑膜炎症和软骨退化的影响。

结果

体外实验表明，TNF-α 是最有效的软骨基质降解酶诱导剂，特立帕肽拮抗 TNF-α 的作用。一致地，来自 TNF-α 转基因小鼠的关节软骨样本比来自野生型小鼠的关节软骨样本含有更多的 MMP-13 阳性软骨细胞。此外，与正常软骨样本相比，人类 OA 软骨中裂解的 II 型胶原更多。

结论

Teriparatide 可通过抑制 TNF-α 介导的 MMP-13 过表达来预防滑膜炎和软骨退化。结合其软骨再生能力，特立帕肽可能是第一种有效的骨关节炎疾病缓解药物。