Fibroblast Insights into the Pathogenesis of Ankylosing Spondylitis

Abstract

Purpose of the Review: Emerging evidence has shown that ankylosing spondylitis fibroblasts (ASFs) act as crucial participants in inflammation and abnormal ossification in ankylosing spondylitis (AS). This review examines the investigations into ASFs and their pathological behavior, which contributes to inflammatory microenvironments and abnormal bone formation. The review spans the period from 2000 to 2023, with a primary focus on the most recent decade. Additionally, the review provides an in-depth discussion on studies on ASF ossification at the cellular level. Recent Findings: ASFs organize immune functions by recruiting immune cells and influencing their differentiation and activation, thus mediate the inflammatory response in the early phase of disease. ASFs promote joint destruction at sites of cartilage and actively promote abnormal ossification by recruiting osteoblasts, differentiation into myofibroblasts or ossification directly. Many signaling pathways and cytokines such as Wnt signaling and BMP/TGF-β signaling are involved in ASF ossification. Summary: ASFs play a key role in AS inflammation and osteogenesis. Further studies are required to elucidate molecular mechanisms behind that and provide new targets and directions for AS diagnosis and treatment from a new perspective of fibroblasts.

Genetic associations in ankylosing spondylitis: circulating proteins as drug targets and biomarkers

“…Pirfenidone possesses anti-inflammatory and antifibrotic properties; its mechanisms include inhibition of TGF-β-induced fibroblast proliferation and suppression of inflammatory mediator production ( 58 ). Given the chronic inflammation and potential fibrosis in the pathological process of AS, including new bone formation ( 59 ), pirfenidone may have potential therapeutic utility in the treatment of AS. Due to the critical role of MAPK14 in regulating inflammation, inhibitors targeting this protein may lead to adverse effects, such as immunosuppression ( 60 ).…”

A review of long non-coding RNAs in ankylosing spondylitis: pathogenesis, clinical assessment, and therapeutic targets

“…For example, the mesenchymal stem cells (MSCs), was reported that may resulting in AS in the conditions of oxidative stress-mediated mitochondrial dysfunction ( Ye et al, 2020 ) and TNF-α-mediated m6A modification of ELMO1 ( Xie et al, 2021 ). Likewise, ankylosing spondylitis fibroblasts (ASFs) can also influence the progression of AS by promoting joint remodeling, affecting fat enrichment and activating as myofibroblasts to form extracellular matrix independent of inflammation ( Liu et al, 2023 ). Given that dysregulation of inflammatory responses are primary manifestations of AS, treatment strategies primarily focus on non-steroidal anti-inflammatory drugs and biologics, including tumor necrosis factor inhibitors and interleukin-17 inhibitors ( Deodhar et al, 2020 ; Tam et al, 2022 ).…”