Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Kyunggi, 14068, South Korea; Institute for Skeletal Aging, Hallym University, Chunchon, 24251, South Korea.
Department of Internal Medicine, Hallym University Sacred Heart Hospital, Kyunggi, 14068, South Korea.
Biochem Biophys Res Commun. 2024 Nov 26;735:150629. doi: 10.1016/j.bbrc.2024.150629. Epub 2024 Sep 3.
Interferon-gamma (IFN-γ) was found to increase in the synovial fluid of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). However, few studies have been conducted to elucidate the role of IFN-γ in cartilage metabolism and regeneration. In this study, we investigated whether cartilage regeneration is driven by interferon-stimulated gene 15 (ISG15) under the control of IFN-γ. IFN-γ significantly increased ITS-induced chondrogenic differentiation of ATDC5 cells. Knockdown of IFN-γ receptor (IFN-γR) inhibited IFN-γ-induced chondrogenic differentiation and reduced ACAN and Col II expression. In addition, ISG15 expression was highly elevated in response to IFN-γ, whereas its expression was downregulated by knockdown of IFN-γR, indicating that ISG15 is closely related to IFN-γ signaling. Furthermore, chondrogenic differentiation and expression of ACAN and Col II were significantly reduced following knockdown of ISG15 in ATDC5 cells despite the presence of IFN-γ. ISGylation of cellular proteins found in chondrogenic differentiated cells was related to activation of IFN-γ signaling. In addition, ISG15/ISGylation was significantly observed in the regenerated cartilage tissue 7 days after FTCI of young mice compared with sham control. Our findings showed that upregulation of ISG15 and/or ISGylation of cellular proteins may play a critical role in cartilage regeneration through activation of IFN-γ signaling.
干扰素-γ（IFN-γ）在类风湿关节炎（RA）和骨关节炎（OA）患者的滑液中被发现增加。然而，很少有研究阐明 IFN-γ 在软骨代谢和再生中的作用。在这项研究中，我们研究了 IFN-γ 是否通过干扰素刺激基因 15（ISG15）的控制来驱动软骨再生。IFN-γ 显著增加了 ITS 诱导的 ATDC5 细胞的软骨分化。IFN-γ 受体（IFN-γR）的敲低抑制了 IFN-γ 诱导的软骨分化，并降低了 ACAN 和 Col II 的表达。此外，ISG15 的表达在 IFN-γ 作用下高度上调，而 IFN-γR 的敲低使其表达下调，表明 ISG15 与 IFN-γ 信号密切相关。此外，尽管存在 IFN-γ，ATDC5 细胞中 ISG15 的敲低也显著降低了软骨分化和 ACAN 和 Col II 的表达。在软骨分化细胞中发现的细胞蛋白的 ISGylation 与 IFN-γ 信号的激活有关。此外，与假对照相比，在年轻小鼠 FTCI 后 7 天，再生软骨组织中明显观察到 ISG15/ISGylation。我们的研究结果表明，ISG15 的上调和/或细胞蛋白的 ISGylation 可能通过激活 IFN-γ 信号在软骨再生中发挥关键作用。
