You are here

Article Text

Article menu
Download PDFPDF
Oral Presentations
ER stress & rheumatic disease
OP0270 Targeting IL-23 Can Attenuate Progression of Spinal Ankylosis in Ankylosing Spondylitis
  1. S. Jo1,
  2. B.S. Koo2,
  3. B.S. Koo2,
  4. I.-H. Sung3,
  5. I.-H. Sung3,
  6. Y.-S. Park4,
  7. Y.-S. Park4,
  8. C.-B. Choi1,
  9. C.-B. Choi1,
  10. T.-H. Kim1,
  11. T.-H. Kim1
  1. 1Department of Rheumatology, Hanyang University Hospital for Rheumatic Disease, Seoul
  2. 2Division of Rheumatology, Department of Internal Medicine, Konkuk University College of Medicine, Chungju
  3. 3Department of Orthopaedic Surgery, Hanyang University Hospital for Rheumatic Disease, Seoul
  4. 4Department of Orthopaedic Surgery, Hanyang University Hospital for Rheumatic Disease, Guri, Korea, Republic Of

Abstract

Background IL-23 has been implicated in the development of ankylosing spondylitis (AS). The role of IL- 23 in AS pathogenesis has emerged as a therapeutic target. This study aimed to clarify that anti IL-23 blockade can prevent progression of bony ankylosing in AS patients.

Objectives We investigated endoplasmic reticulum (ER) stress and IL-23 cytokine could play a role in human bone-derived osteoblast cells and blocking it leads to regulation of bone-related genes and/or preventing bone ankylosis in AS.

Methods Primary human osteoblast cells were isolated from diced bones of facet joints which were taken from surgical operation of 8 AS patients and 8 healthy controls (HC). The tissues of facet joints in AS were stained and compared with those of HC. Osteoblast differentiation- and ER stress-related genes were determined by quantitative RT-PCR, immunoblotting, immunofluorescence, and immunohistochemistry. Osteoblast activity of all bones-derived osteoblast cells was confirmed by Alkaline Phosphatase activity (ALP) and Alizarin Red (ARS) staining. The ER stress by BIX, selective BIP inducer X, in the regulation of IL-23 expression and secretion was evaluated by quantitative RT-PCR and ELISA.

Results We found that elevated RUNX2, BIP, and IL-23 protein expressions were observed at osteoblast cells in human AS compared to HC. In addition, mRNA levels of bone differentiation (ALP, BMP2, COL1A, RUNX2, C/EBPβ, OPG, and OCN) and ER stress (BIP and CHOP)-related genes were highly expressed in human AS. In particular, IL-23 and RUNX2 expressions were significantly increased in AS. BIX-mediated ER stress stimulated induction of osteoblast activity and IL-23 secretion via modulating RUNX2 and C/EBPβ genes. Intriguingly, RUNX2 Knockdown by shRNA impeded ER stress-induced effects. Moreover, osteoblast activity and RUNX2 expression in AS were significantly reduced by IL-23 blockers, but not TNFα blockers.

Conclusions This is the first report to show that ER stress, osteoblastic activity, and IL-23 expression in AS were increased compared to HC, suggesting that sustained ER stress induces osteoblast activity and IL-23 expression. Notably, these effects in AS were reduced by IL-23 blockade. Taken together, our results supported that blocking IL-23 may represent a promising therapeutic target to assist and prevent bony progression in AS.

Disclosure of Interest None declared

https://doi.org/10.1136/annrheumdis-2016-eular.3872

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.