Vertebral Osteoporosis in Systemic Lupus Erythematosus: A Possible Involvement of Inflammation-Related Osteoblast Ferroptosis

作者：Zhaobai Lao, Xiaogang Chen, Xin Chen, Helou Zhang, Zhiguo Zhang, Yishan Bian, Chengcong Zhou, Kun Tian, Hongting Jin, Fangda Fu, Chengliang Wu, Kaifeng Gan, Hongfeng Ruan · 发表于：Journal of Inflammation Research · 年份：2025 · DOI：10.2147/jir.s523051 · 被引用次数：4 · 研究领域：Ferroptosis and cancer prognosis、Bone Metabolism and Diseases、TGF-β signaling in diseases

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by immune system dysregulation and the production of autoantibodies, leading to widespread inflammation and multi-organ damage. Despite clinical observations have shown that approximately 1.4– 68.7% of SLE patients develop vertebral osteoporosis (OP), the underlying mechanisms remain poorly defined. This study utilized the MRL/ lpr mouse model, which effectively replicates human SLE manifestations, to investigate the impact of SLE on vertebral bone homeostasis. Methods: Female MRL/ lpr mice were employed to investigate SLE-induced bone loss. The study comprehensively evaluated bone structural changes through micro-CT analysis, histological assessment, and bone metabolic markers. Specifically, we analyzed trabecular parameters (TV, BV, BV/TV, Tb.Th), inflammatory cytokine profiles (TNF-α, IL-6, IL-1β, IL-18), osteogenic markers (RUNX2, OSTERIX, ALP, OPG), osteoclastogenic indicators (TRAP, RANKL, CTSK), and ferroptosis-related proteins (FACL4, FTH1, GPX4). Results: SLE progression in MRL/ lpr mice led to significant vertebral bone loss and OP phenotype, evidenced by reduced bone volume fraction (BV/TV) and trabecular thickness (Tb.Th). The inflammatory microenvironment was characterized by elevated TNF-α and IL-6 levels, which disrupted bone homeostasis by suppressing RUNX2, OSTERIX, and OPG expression while enhancing RANKL signaling. Mechanistically, SLE induced ferroptosis through in...