HLA-B27–mediated activation of TNAP phosphatase promotes pathogenic syndesmophyte formation in ankylosing spondylitis

摘要: 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 (AS MSCs) within the enthesis involved in to delineate that HLA-B27-mediated spliced X-box-binding protein 1 (sXBP1)/retinoic acid receptor-β (RARB)/tissue-nonspecific alkaline phosphatase (TNAP) axis accelerated mineralization MSCs, which was independent Runt-related transcription factor 2 (Runx2). An animal model mimicking pathological bony appositions established by implantation MSCs into lumbar spine NOD-SCID mice. We found TNAP inhibitors, including levamisole pamidronate, inhibited MSC vitro blocked vivo. Furthermore, demonstrated serum bone-specific (BAP) level potential prognostic biomarker predict with high risk for radiographic progression. Our study highlights importance activation sXBP1/RARB/TNAP pathogenesis provides new strategy diagnosis prevention progression AS.