骨關節炎 (Osteoarthritis, OA) 屬於退化性關節炎疾病的一種，主要病徵有關節破壞、軟骨下骨硬化、骨刺形成、關節囊及滑膜發炎等。介白素 20 (Interleukin-20, IL-20) 屬於介白素 10 家族的一員，其成員包含有介白素 10、19、20、22、24 及 26。根據文獻得知 IL-20 參與類風溼性關節炎 (Rheumatoid arthritis, RA) 致病機轉中，且打入可溶性 IL-20R1 受體可以降低 collagen-induced arthritis (CIA) 動物模式的嚴重程度。因此，IL-20 在 RA 致病過程中扮演促進的角色。然而，目前不清楚 IL-20 在 OA 的病理機制中扮演的角色，因此本研究主要目的是探討 IL-20 是否也參與 OA 的致病機轉。首先，我們發現在 OA 病人的滑膜組織、軟骨及滑膜纖維母細胞 (OA SFs) 都有 IL-20 與其受體的表現。IL-20 處理 OA SFs後也能誘發 MCP-1 及 IL-6 的表現。利用手術誘發 OA 動物模式中發現，IL-20 與其受體 IL-20R1 都有表現在滑膜纖維母細胞 (OA SFs) 及軟骨細胞 (OA CCs) 上。其中，OA SFs 中 IL-20 表現量高於健康大鼠 SFs。IL-20 處理 OA SFs 後會誘發 TNF-α、IL-1β、IL-6、MMP1 及 MMP-13 表現，也促進 ERK-1/2 及 JNK 磷酸化表現。在動物實驗中，IL-20 單株抗體 (7E) 可以降低關節腫脹、軟骨破壞及滑膜中 IL-1 的表現。由以上實驗結果推測 IL-20 在 OA 的致病過程中可能扮演一個促進發炎的角色。抑制 IL-20 的功能或許可以提供一種新的治療 OA 的策略。

Osteoarthritis (Osteoarthritis, OA) is a degenerative joint disease characterized by cartilage breakdown, subchondral sclerosis, osteophyte formation, and alterations to the joint capsule and inflammation of the synovial membrane. IL-20 belongs to the IL-10 family, which consists of IL-10, IL-19, IL-20, IL-22, IL-24, and IL-26. We previously showed that IL-20 was involved in RA, and the soluble receptor of IL-20R1 reduced the severity of collagen-induced arthritis (CIA). Therefore, IL-20 is a promoting factor during the progression of (Rheumatoid arthritis, RA). However, little is known about the function of IL-20 in OA. Therefore, we explored whether IL-20 is involved in the pathogenesis of OA. We found that IL-20 and its receptors were expressed in synovial tissue, cartilage and primary synovial fibroblast isolated from OA patients (OASFs). IL-20 induced MCP-1 and IL-6 expression in OASFs. In our rat OA model, IL-20 and its receptors were expressed in chondrocytes and synovial fibroblasts. IL-20 was significantly increased in SFs derived from OA rats compared to healthy rats. IL-20 also induced the expression of TNF-α, IL-1β, IL-6, MMP1, and MMP-13 in SF derived from OA rats. IL-20 activated the phosphorylation of ERK-1/2 and JNK in SFs derived from OA rats. In vivo, anti-IL-20 antibody (7E) reduced the joint swelling, cartilage damage and inhibited the expression of IL-1β in OA rats. These results suggest that IL-20 acts as a pro-inflammatory molecule and plays a pivotal role in the pathogenesis of OA. Blocking IL-20 signaling may be a potential therapeutic strategy for treating OA.

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