Background/Purpose: Ankylosing spondylitis (AS) is a chronic inflammatory arthritis that predominantly affects the axial skeleton. Disease progression in AS is marked by new bone formation in the spine resulting in progressive vertebral fusion. The presence of various immune cell subsets and cytokines at sites of inflammation has been reported. However their specific role in mediating bone fusion is not understood. Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine with pleiotropic functions and has been implicated in a variety of inflammatory diseases. Herein, we intend to identify a role for MIF in triggering bone formation in AS.

Methods: For the initial analysis, AS patients who satisfied the Modified New York Criteria and healthy controls were included. Among AS patients, non-progressors had no increase in the modified Stoke’s AS Spinal Score (mSASSS) despite a minimum 4 years of follow up and progressors had ≥2 mSASSS units/year of progression and syndesmophyte formation based on sequential X-rays. MIF levels were estimated by ELISA in stored serum of AS patients and healthy controls and synovial fluid samples from AS, rheumatoid arthritis (RA) and osteoarthritis (OA) patients. The human osteosarcoma cell line Saos-2 was treated with recombinant human MIF in the presence of osteogenic conditions and the extent of mineralization was visualized by Alizarin Red S staining and quantified using Image J analysis. Active β-catenin was detected by western blotting and normalized using  Glyceradehyde 3-phosphate dehydrogenase (GAPDH) as control.

Results: AS patients had significantly higher serum MIF levels as compared to healthy controls (p<0.0001). Baseline MIF levels were significantly higher in progressors compared to non-progressors (p<0.04). Saos-2 cells cultured in-vitro in an inflammatory milieu in the presence of recombinant human MIF showed enhanced mineralization in a dose dependent manner (p<0.03). Also, we found that MIF levels were markedly elevated in the synovial fluid of AS patients as compared to those suffering from RA or OA (p<0.04). Western blot analysis showed an induction of active β-catenin in MIF treated osteoblasts.

Conclusion: Serum MIF levels are significantly higher in AS patients compared to healthy controls. MIF levels in AS synovial fluid is higher than RA and OA. The study identifies a previously unknown role for MIF in bone formation in AS by having a direct stimulatory effect on osteoblastogenesis possibly by triggering the Wnt/β-catenin pathway.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/macrophage-migration-inhibitory-factor-a-novel-biomarker-in-ankylosing-spondylitis-that-can-drive-spinal-fusion/