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  3. Osteoclast-derived DEL1 promotes pathological bone formation in ankylosing spondylitis by regulating RUNX2 expression in osteoblasts

Osteoclast-derived DEL1 promotes pathological bone formation in ankylosing spondylitis by regulating RUNX2 expression in osteoblasts

  • Differentiation. 2026 May-Jun:149:100962. doi: 10.1016/j.diff.2026.100962.
Seung Hoon Lee 1,  Chanhyeok Jeon 1,  Dongju Kim 1,  Hye-Ryeong Jo 1,  Eunae Ko 1,  Jeehee Youn 2,  Seunghun Lee 3,  Sung Hoon Choi 4,  Ye-Soo Park 5,  Sungsin Jo 6,  Tae-Hwan Kim 7
Affiliations

Affiliations

  • 1 Hanyang University Institute for Rheumatology Research (HYIRR), Hanyang University, Seoul, 04763, South Korea.
  • 2 Department of Anatomy & Cell Biology, College of Medicine, Hanyang University, Seoul, 04763, South Korea.
  • 3 Department of Radiology, Hanyang University Hospital for Rheumatic Diseases, Seoul, 04763, South Korea.
  • 4 Department of Orthopaedic Surgery, Hanyang University Seoul Hospital, Seoul, 04763, South Korea.
  • 5 Department of Orthopaedic Surgery, Guri Hospital, Hanyang University College of Medicine, Guri, 11923, South Korea.
  • 6 Department of Biology, College of Natural Sciences, Soonchunhyang University, Asan, Chungcheongnam-do, 31538, South Korea. Electronic address: [email protected].
  • 7 Hanyang University Institute for Rheumatology Research (HYIRR), Hanyang University, Seoul, 04763, South Korea; Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, 04763, South Korea. Electronic address: [email protected].
PMID: 42128469 DOI: 10.1016/j.diff.2026.100962
Abstract

Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by ectopic bone formation. We investigated in vitro and in vivo the role of developmental endothelial locus-1 (DEL1) on new bone formation and determined the association between DEL1 and spinal progression in AS.

Methods: DEL1 levels were measured in plasma and facet joint tissues from patients with AS, and in osteoclast-derived medium. Human osteoblast precursor cells were treated with recombinant DEL1 protein and cilengitide trifluoroacetate, an αvβ3 Integrin Inhibitor, to evaluate their effects on osteoblast differentiation markers. A curdlan-injected SKG mouse model was used to mimic AS pathogenesis. Three weeks after curdlan injection, recombinant DEL1 protein or cilengitide was administered, and the mice's ankle thickness was assessed. The mice were sacrificed after six weeks, and micro-CT and histological analyses were performed.

Results: DEL1 expression significantly increased during osteoclast differentiation, peaked at the terminal stage, and correlated with disease progression in AS mice. Systemic plasma DEL1 levels were not different between patients with AS and the control group, but were positively correlated with structural damage (mSASSS; R = 0.3433, p = 0.0195). DEL1 pro-osteogenic effects were neutralized by cilengitide, which attenuated DEL1-induced RUNX2 expression and matrix mineralization.

Conclusion: Our findings establish DEL1 as a key osteoclast-derived coupling factor that drives new bone formation in AS. DEL1 promotes pathological bone formation and osteoblast differentiation by signaling through the Integrin αVβ3-RUNX2 axis; targeting this pathway may offer a novel approach to prevent structural damage in patients with AS.

Keywords

Ankylosing spondylitis; Developmental endothelial locus-1 (DEL1); Integrin αVβ3; New bone formation; Osteoblast differentiation; osteoclast.

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