Background Ankylosing spondylitis is characterized by new bone formation and bone loss, associated with inflammation, which are mediated by cytokine-signaling pathways. High mobility group box 1 (HMGB1) protein, is a nonhistone nuclear protein, which is secreted by inflammatory cells, is also defined as a bone-active cytokine. Recent studies have shown that RANKL induces HMGB1 release and it is required for RANKL-induced osteoclastogenesis in vitro and in vivo.
Objectives To investigate the relationship of serum HMGB1 levels with RANKL/ Osteoprotegerin (OPG) axis and clinical and radiographic parameters in patients with AS.
Methods In this cross-sectional study, serum samples for total HMGB1, sRANKL and OPG were detected from 54 tumour necrosis factor (TNF) inhibitor naive patients with AS according to the modified New York criteria [mean age 34.9 years (S.D. 7.1); duration of symptoms 8.6 years (S.D. 4.2); male gender 38 patients (70.4%)] and 26 healthy controls. ESR, CRP, Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI) were assessed for each patient. Bone mineral density was measured using dual-energy X-ray absorptiometry (DXA) at lumbar spine (L2–L4) and proximal femur. Lumbar spine radiographs were scored using the modified Stoke AS Spine Score (mSASSS).
Results Serum HMGB1 levels were relatively higher in patients with AS than HCs however no statistically significant in each other. Serum HMGB1 levels correlated with CRP (rho=0.368 and P=0.006), ASDAS-CRP (rho=0.358 and p=0.008) and BASDAI (rho=0.334 and p=0.014) and BASFI (rho=0.355 and p=0.008) in patients with AS. CRP and ASDAS-CRP showed more correlated to HMGB1 serum levels than BASDAI. There was no significant correlation between HMGB1 levels with sRANKL, OPG, mSASSS and spine or femur BMD values. In addition, serum OPG levels and the ratio of sRANKL to OPG from AS patients were significantly higher than those of HCs.
Conclusions This study showed that levels of HMGB1 in the sera of AS patients, are increased compared to healty controls. Serum HMGB1 levels are related to BASDAI, ASDAS-CRP, BASFI and CRP in patients with AS. Different results in the literature on serum HMGB1 levels as well as our results support the hypothesis that HMGB1 plays a role in the pathogenesis of AS. According to our knowledge, it is the first trial evaluating association between serum HMGB1 levels with sRANKL-OPG axis, bone mineral density and new bone formation in AS patients and it seems not to be related for these conditions.
Zhou Z, Han JY, Xi CX, et al. J Bone Miner Res. HMGB1 regulates RANKL-induced osteoclastogenesis in a manner dependent on RAGE.2008 Jul;23(7):1084–96.
Bidwell JP, Yang J, Robling AG. Is HMGB1 an osteocyte alarmin? J Cell Biochem. 2008 Apr 15;103(6);1671–80.
Acknowledgements Grant Support: by Erciyes University Council of Scientific Investigations (Project code: TTU-2014–5575).
Disclosure of Interest None declared
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