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Spondyloarthritis
Original article
No evidence for a direct role of HLA-B27 in pathological bone formation in axial SpA
  1. Barbara Neerinckx1,2,
  2. Simon Kollnberger3,
  3. Jacqueline Shaw4 and
  4. Rik Lories1,2
  1. 1 Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, Leuven, Belgium
  2. 2 Division of Rheumatology, UZ Leuven, Leuven, Belgium
  3. 3 Cardiff Institute of Infection and Immunity, Cardiff University, Cardiff, UK
  4. 4 Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Botnar Research Centre, Oxford University, Oxford, UK
  1. Correspondence to Professor Rik Lories; rik.lories{at}uz.kuleuven.be

Abstract

Objective The strong genetic association between HLA-B27 and ankylosing spondylitis has been known for over 40 years. HLA-B27 positivity is possibly associated with severity of ankylosis. We studied the in vitro and in vivo impact of HLA-B27 in models of chondrogenesis and osteogenesis.

Methods Different in vitro differentiation systems were used to mimic endochondral and direct bone formation. ATDC5 cells and primary human periosteum-derived cells (hPDCs) were transduced with lentiviral vectors expressing HLA-B27 or HLA-B7. These cells and limb bud cells (from HLA-B27 transgenic and wild-type (WT) mice) were cultured in micromasses. To study direct osteogenesis in hPDCs, cells were cultured as monolayers and stimulated with osteogenic media. Chondrogenesis (COL2, ACAN, COL10) and osteogenesis (OSC, ALP, RUNX2) marker expression was studied by quantitative RT-PCR. Colorimetric tests were performed to measure proteoglycans, mineralization and collagens. Collagen antibody-induced arthritis (CAIA) was induced in HLA-B27 transgenic and WT mice. Clinical scoring and µCTs were performed. Statistical analyses were performed by two-way ANOVA.

Results There was no difference in chondrogenesis markers or in colorimetric tests between HLA-B27+ and HLA-B7+ micromasses. Expression of osteogenesis markers and Alizarin red staining was comparable in the HLA-B27+ and the HLA-B7+ hPDCs in monolayers. HLA-B27 transgenic mice showed more severe arthritis compared with WT mice in the CAIA model. µCT analysis showed no increased bone formation in HLA-B27 transgenic mice.

Conclusion HLA-B27 seems to enhance joint inflammation in the CAIA model. We could not document a direct effect of HLA-B27 on chondrogenesis or osteogenesis.

  • axial spondyloarthritis
  • HLA-B27
  • ankylosis
  • osteogenesis
  • chondrogenesis

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/rmdopen-2017-000451

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    Footnotes

    • Contributors BN and RL initiated the study and wrote the manuscript. BN performed experiments and developed reagents. SK and JS developed and optimized the used plasmids. All authors were involved in drafting the article or revising it critically for important intellectual content. All authors approved the final version to be published.

    • Competing interests None declared.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data sharing statement All data supporting the findings of this study are available within the article and its supplementary files, or available from the authors upon request.