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The complement factor H-related protein-5 (CFHR5) exacerbates pathological bone formation in ankylosing spondylitis

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Author(s)
Ji-Hyun LeeSeung Hoon LeeChanhyeok JeonJinil HanSang-Hyon KimJeehee YounYe-Soo ParkTae-Jong KimJong-Seo KimSungsin JoTae-Hwan KimChang-Nam Son
Keimyung Author(s)
Kim, Sang Hyon
Department
Dept. of Internal Medicine (내과학)
Journal Title
J Mol Med (Berl)
Issued Date
2024
Volume
102
Issue
4
Keyword
ASCFHR5MineralizationOsteoprogenitorsPathological bone formation
Abstract
Ankylosing spondylitis (AS) is a chronic inflammatory disease, characterized by excessive new bone formation. We previously reported that the complement factor H-related protein-5 (CFHR5), a member of the human factor H protein family, is significantly elevated in patients with AS compared to other rheumatic diseases. However, the pathophysiological mechanism underlying new bone formation by CFHR5 is not fully understood. In this study, we revealed that CFHR5 and proinflammatory cytokines (TNF, IL-6, IL-17A, and IL-23) were elevated in the AS group compared to the HC group. Correlation analysis revealed that CFHR5 levels were not significantly associated with proinflammatory cytokines, while CFHR5 levels in AS were only positively correlated with the high CRP group. Notably, treatment with soluble CFHR5 has no effect on clinical arthritis scores and thickness at hind paw in curdlan-injected SKG, but significantly increased the ectopic bone formation at the calcaneus and tibia bones of the ankle as revealed by micro-CT image and quantification. Basal CFHR5 expression was upregulated in AS-osteoprogenitors compared to control cells. Also, treatment with CFHR5 remarkedly induced bone mineralization status of AS-osteoprogenitors during osteogenic differentiation accompanied by MMP13 expression. We provide the first evidence demonstrating that CFHR5 can exacerbate the pathological bone formation of AS. Therapeutic modulation of CFHR5 could be promising for future treatment of AS. KEY MESSAGES: Serum level of CFHR5 is elevated and positively correlated with high CRP group of AS patients. Recombinant CFHR5 protein contributes to pathological bone formation in in vivo model of AS. CFHR5 is highly expressed in AS-osteoprogenitors compared to disease control. Recombinant CFHR5 protein increased bone mineralization accompanied by MMP13 in vitro model of AS.
Keimyung Author(s)(Kor)
김상현
Publisher
School of Medicine (의과대학)
Type
Article
ISSN
1432-1440
Source
https://link.springer.com/article/10.1007/s00109-024-02428-6
DOI
10.1007/s00109-024-02428-6
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/45508
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Internal Medicine (내과학)
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