ArticleThe Journal of clinical investigation2019
HLA-B27-mediated activation of TNAP phosphatase promotes pathogenic syndesmophyte formation in ankylosing spondylitis.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42 citing papers in PubMed, 71 citations in OpenAlex.
- Severe aplastic anemia as a rare autoimmune complication of ankylosing spondylitis: A rare case report.Medicine · 2026Article
- The 60Rheumatology and immunology research · 2026Article
- Progression to Radiographic Axial Spondyloarthritis: A Narrative Review on Timeline and Novel Prediction Factors.International journal of molecular sciences · 2026Review
- Restoring immune homeostasis in the spinal microenvironment: targeting mechano-inflammation and immunometabolic reprogramming.Frontiers in immunology · 2026Review
- Research Advances on the Mechanism and Diagnosis of Bone Bridging in Ankylosing Spondylitis.Orthopedic research and reviews · 2026Review
- Mechanical growth factor inhibited syndesmophyte formation and the progression of osteoarthritis and ankylosing spondylitis-like symptoms in HLA-B27/Hu-β2m transgenic rats.Arthritis research & therapy · 2025Article
- Recent Advances in the Immunopathology of Axial Spondyloarthritis: with and without HLA-B27.Current rheumatology reports · 2025Review
- HLA-B27 and spondyloarthritis: at the crossroads of innate and adaptive immunity.Nature reviews. Rheumatology · 2025Review
- Decoding the inflammatory-osteogenic axis in ankylosing spondylitis: mechanisms, dysregulation, and emerging therapeutic interventions.Frontiers in immunology · 2025Review
- Breaking boundaries in ankylosing spondylitis: how innovative cell therapies reshape immunity, drive cutting-edge advances, and face future challenges.Frontiers in immunology · 2025Review
- Application of methylation in the diagnosis of ankylosing spondylitis.Clinical rheumatology · 2024Review
- IRE1α pathway: A potential bone metabolism mediator.Cell proliferation · 2024Review
- Osteoimmunology of Spondyloarthritis.International journal of molecular sciences · 2023Review
- The bone marrow side of axial spondyloarthritis.Nature reviews. Rheumatology · 2023Review
- Syndesmophyte Growth in Ankylosing Spondylitis: from Laboratory to Bedside.Current rheumatology reports · 2023Review
- Association between changes in serum alkaline phosphatase levels and radiographic progression in ankylosing spondylitis.Scientific reports · 2023Article
- MEG3 alleviates ankylosing spondylitis by suppressing osteogenic differentiation of mesenchymal stem cells through regulating microRNA-125a-5p-mediated TNFAIP3.Apoptosis : an international journal on programmed cell death · 2023Article
- Uncovering the Underworld of Axial Spondyloarthritis.International journal of molecular sciences · 2023Review
- Paradoxical Effects of Endoplasmic Reticulum Aminopeptidase 1 Deficiency on HLA-B27 and Its Role as an Epistatic Modifier in Experimental Spondyloarthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2023Article
- Fibroblast Insights into the Pathogenesis of Ankylosing Spondylitis.Journal of inflammation research · 2023Review
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Authors and funding
15 authors at 9 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ankylosing spondylitis (AS) is a type of axial inflammation. Over time, some patients develop spinal ankylosis and permanent disability; however, current treatment strategies cannot arrest syndesmophyte formation completely. Here, we used mesenchymal stem cells (MSCs) from AS patients (AS MSCs) within the enthesis involved in spinal ankylosis to delineate that the HLA-B27-mediated spliced X-box-binding protein 1 (sXBP1)/retinoic acid receptor-β (RARB)/tissue-nonspecific alkaline phosphatase (TNAP) axis accelerated the mineralization of AS MSCs, which was independent of Runt-related transcription factor 2 (Runx2). An animal model mimicking AS pathological bony appositions was established by implantation of AS MSCs into the lumbar spine of NOD-SCID mice. We found that TNAP inhibitors, including levamisole and pamidronate, inhibited AS MSC mineralization in vitro and blocked bony appositions in vivo. Furthermore, we demonstrated that the serum bone-specific TNAP (BAP) level was a potential prognostic biomarker to predict AS patients with a high risk for radiographic progression. Our study highlights the importance of the HLA-B27-mediated activation of the sXBP1/RARB/TNAP axis in AS syndesmophyte pathogenesis and provides a new strategy for the diagnosis and prevention of radiographic progression of AS.
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