Jiang Lijuan, Qiu Wenlin, Wang Xuefei, Duan Xiaoru, Han Xiaoxiao, Yu Tong, Wen Shenghui, Luo Zhijun, Feng Ruizhi, Teng Yao, Yin Haifeng, Hedrich Christian M, Deng Guo-Min
Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
Department of Pediatric Rheumatology, Alder Hey Children's NHS Foundation Trust Hospital, Liverpool, UK.
iScience. 2023 Aug 26;26(10):107749. doi: 10.1016/j.isci.2023.107749. eCollection 2023 Oct 20.
Glucocorticoid-induced osteoporosis (GIOP) is a severe and common complication of long-term usage of glucocorticoids (GCs) and lacks of efficient therapy. Here, we investigated the mechanism of anti-inflammation effect and osteoclastogenesis side effect of GCs and immunoglobulin G (IgG) treatment against GIOP. GCs inhibited SLE IgG-induced inflammation, while IgG inhibited GCs-induced osteoclastogenesis. FcγRI and glucocorticoid receptor (GR) were found directly interacted with each other. GCs and IgG could reduce the expression of FcγRI on macrophages. The deficiency of FcγRI affected osteoclastogenesis by GCs and systemic lupus erythematosus (SLE) IgG-induced inflammation. Also, IgG efficiently reduced GIOP in mice. These data showed that GCs could induce osteoporosis and inhibit IgG-induced inflammation through FcγRI while IgG efficiently suppressed osteoporosis induced by GCs through FcγRI. Hence, our findings may help in developing a feasible therapeutic strategy against osteoporosis, such as GIOP.
糖皮质激素诱导的骨质疏松症（GIOP）是长期使用糖皮质激素（GCs）的一种严重且常见的并发症，并且缺乏有效的治疗方法。在此，我们研究了GCs和免疫球蛋白G（IgG）治疗GIOP的抗炎作用机制及破骨细胞生成副作用。GCs抑制SLE IgG诱导的炎症，而IgG抑制GCs诱导的破骨细胞生成。发现FcγRI与糖皮质激素受体（GR）直接相互作用。GCs和IgG可降低巨噬细胞上FcγRI的表达。FcγRI的缺乏影响了GCs诱导的破骨细胞生成以及系统性红斑狼疮（SLE）IgG诱导的炎症。此外，IgG有效减轻了小鼠的GIOP。这些数据表明，GCs可通过FcγRI诱导骨质疏松并抑制IgG诱导的炎症，而IgG通过FcγRI有效抑制GCs诱导的骨质疏松。因此，我们的研究结果可能有助于制定针对骨质疏松症（如GIOP）的可行治疗策略。
