Vertebral Osteoporosis in Systemic Lupus Erythematosus: A Possible Involvement of Inflammation-Related Osteoblast Ferroptosis
Zhaobai Lao,1,* Xiaogang Chen,2,* Xin Chen,1,* Helou Zhang,1 Zhiguo Zhang,1 Yishan Bian,1 Chengcong Zhou,1 Kun Tian,2 Hongting Jin,1 Fangda Fu,1 Chengliang Wu,1 Kaifeng Gan,3 Hongfeng Ruan1 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Dove Medical Press
2025-04-01
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| Series: | Journal of Inflammation Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/vertebral-osteoporosis-in-systemic-lupus-erythematosus-a-possible-invo-peer-reviewed-fulltext-article-JIR |
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| Summary: | Zhaobai Lao,1,* Xiaogang Chen,2,* Xin Chen,1,* Helou Zhang,1 Zhiguo Zhang,1 Yishan Bian,1 Chengcong Zhou,1 Kun Tian,2 Hongting Jin,1 Fangda Fu,1 Chengliang Wu,1 Kaifeng Gan,3 Hongfeng Ruan1 1Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Traditional Chinese Medicine), Hangzhou, Zhejiang, 310053, People’s Republic of China; 2Department of Orthopaedic Surgery, The Third Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, 310005, People’s Republic of China; 3Department of Orthopaedic Surgery, The Affiliated LiHuiLi Hospital of Ningbo University, Ningbo, Zhejiang, 315040, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kaifeng Gan, Department of Orthopaedic Surgery, The Affiliated LiHuiLi Hospital of Ningbo University, 57 Xingning Road, Ningbo, Zhejiang, 315040, People’s Republic of China, Email gankaifeng@163.com Hongfeng Ruan, Institute of Orthopaedics and Traumatology, The First Affiliated Hospital of Zhejiang Chinese Medical University, 548 Binwen Road, Hangzhou, 310053, People’s Republic of China, Email rhf@zcmu.edu.cnBackground: 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 increased FACL4 and FTH1 expression coupled with decreased GPX4 levels, leading to impaired osteoblast function and enhanced osteoclast activity.Conclusion: SLE-associated vertebral OP is mediated by inflammation-driven ferroptosis, disrupting the balance between bone formation and resorption, offering novel insights into potential therapeutic strategies for managing bone loss in SLE patients.Keywords: systemic lupus erythematosus, vertebral osteoporosis, inflammation, ferroptosis, osteoblast dysfunction |
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| ISSN: | 1178-7031 |