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No evidence for a direct role of HLA-B27 in pathological bone formation in axial SpA
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: Di...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BMJ Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574451/ https://www.ncbi.nlm.nih.gov/pubmed/28879048 http://dx.doi.org/10.1136/rmdopen-2017-000451 |
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author | Neerinckx, Barbara Kollnberger, Simon Shaw, Jacqueline Lories, Rik |
author_facet | Neerinckx, Barbara Kollnberger, Simon Shaw, Jacqueline Lories, Rik |
author_sort | Neerinckx, Barbara |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5574451 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BMJ Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-55744512017-09-06 No evidence for a direct role of HLA-B27 in pathological bone formation in axial SpA Neerinckx, Barbara Kollnberger, Simon Shaw, Jacqueline Lories, Rik RMD Open Spondyloarthritis 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. BMJ Publishing Group 2017-06-29 /pmc/articles/PMC5574451/ /pubmed/28879048 http://dx.doi.org/10.1136/rmdopen-2017-000451 Text en © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted. 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/ |
spellingShingle | Spondyloarthritis Neerinckx, Barbara Kollnberger, Simon Shaw, Jacqueline Lories, Rik No evidence for a direct role of HLA-B27 in pathological bone formation in axial SpA |
title | No evidence for a direct role of HLA-B27 in pathological bone formation in axial SpA |
title_full | No evidence for a direct role of HLA-B27 in pathological bone formation in axial SpA |
title_fullStr | No evidence for a direct role of HLA-B27 in pathological bone formation in axial SpA |
title_full_unstemmed | No evidence for a direct role of HLA-B27 in pathological bone formation in axial SpA |
title_short | No evidence for a direct role of HLA-B27 in pathological bone formation in axial SpA |
title_sort | no evidence for a direct role of hla-b27 in pathological bone formation in axial spa |
topic | Spondyloarthritis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5574451/ https://www.ncbi.nlm.nih.gov/pubmed/28879048 http://dx.doi.org/10.1136/rmdopen-2017-000451 |
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