Syndesmophyte growth in ankylosing spondylitis occurs via specific osteoimmunologic mechanisms.
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The retrieved literature indicates that syndesmophyte growth in ankylosing spondylitis is driven by inflammatory and immune-mediated processes, linking activated immune cells, cytokines, and signaling pathways like Wnt to abnormal bone formation.
The concept of osteoimmunology is based on growing insight into the links between the immune system and bone at the anatomical, vascular, cellular, and molecular levels. In both rheumatoid arthritis (RA) and ankylosing spondylitis (AS), bone is a target of inflammation. Activated immune cells at sites of inflammation produce a wide spectrum of cytokines in favor of increased bone resorption in RA and AS, resulting in bone erosions, osteitis, and peri-inflammatory and systemic bone loss. Peri-inflammatory bone formation is impaired in RA, resulting in non-healing of erosions, and this allows a local vicious circle of inflammation between synovitis, osteitis, and local bone loss. In contrast, peri-inflammatory bone formation is increased in AS, resulting in healing of erosions, ossifying enthesitis, and potential ankylosis of sacroiliac joints and intervertebral connections, and this changes the biomechanical competence of the spine. These changes in bone remodeling and structure contribute to the increased risk of vertebral fractures (in RA and AS) and non-vertebral fractures (in RA), and this risk is related to severity of disease and is independent of and superimposed on background fracture risk. Identifying patients who have RA and AS and are at high fracture risk and considering fracture prevention are, therefore, advocated in guidelines. Local peri-inflammatory bone loss and osteitis occur early and precede and predict erosive bone destruction in RA and AS and syndesmophytes in AS, which can occur despite clinically detectable inflammation (the so-called 'disconnection'). With the availability of new techniques to evaluate peri-inflammatory bone loss, osteitis, and erosions, peri-inflammatory bone changes are an exciting field for further research in the context of osteoimmunology.
Ankylosing spondylitis (AS) is an autoinflammatory disease that manifests with the unique feature of enthesitis. Gut microbiota, HLA-B*27, and biomechanical stress mutually influence and interact resulting in setting off a flame of inflammation. In the HLA-B*27 positive group, dysbiosis in the gut environment disrupts the barrier to exogenous bacteria or viruses. Additionally, biomechanical stress induces inflammation through enthesial resident or gut-origin immune cells. On this basis, innate and adaptive immunity can propagate inflammation and lead to chronic disease. Finally, bone homeostasis is regulated by cytokines, by which the inflamed region is substituted into new bone. Agents that block cytokines are constantly being developed to provide diverse therapeutic options for preventing the progression of inflammation. In addition, some antibodies have been shown to distinguish disease selectively, which support the involvement of autoimmune immunity in AS. In this review, we critically analyze the complexity and uniqueness of the pathogenesis with updates on the findings of immunity and provide new information about biologics and biomarkers.
Several rheumatologic diseases are primarily distinguished by their involvement of bone tissue, which not only serves as a mere target of the condition but often plays a pivotal role in its pathogenesis. This scenario is particularly prominent in chronic inflammatory arthritis such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). Given the immunological and systemic nature of these diseases, in this review, we report an overview of the pathogenic mechanisms underlying specific bone involvement, focusing on the complex interactions that occur between bone tissue's own cells and the molecular and cellular actors of the immune system, a recent and fascinating field of interest defined as osteoimmunology. Specifically, we comprehensively elaborate on the distinct pathogenic mechanisms of bone erosion seen in both rheumatoid arthritis and spondyloarthritis, as well as the characteristic process of aberrant bone formation observed in spondyloarthritis. Lastly, chronic inflammatory arthritis leads to systemic bone involvement, resulting in systemic bone loss and consequent osteoporosis, along with increased skeletal fragility.
<h4>Purpose of the review</h4>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.<h4>Recent findings</h4>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.<h4>Summary</h4>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.
Systemic connective tissue disorders constitute a heterogenous group of autoimmune diseases with the potential to affect a range of organs. Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune inflammatory disease affecting the joints. Systemic lupus erythematosus (SLE) may manifest with multiple system involvement as a result of inflammatory response to autoantibodies. Spondyloarthropathies (SpAs) such as ankylosing spondylitis (AS) or psoriatic arthritis (PsA) are diseases characterised by the inflammation of spinal joints, paraspinal tissues, peripheral joints and enthesitis as well as inflammatory changes in many other systems and organs. Physiologically, sclerostin helps to maintain balance in bone tissue metabolism through the Wnt/β-catenin pathway, which represents a major intracellular signalling pathway. This review article aims to present the current knowledge on the role of sclerostin in the Wnt/β-catenin pathway and its correlation with clinical data from RA, SLE, AS and PsA patients.
Introduction. Syndesmophyte, which is the hallmark of ankylosing spondylitis (AS), is a vertically oriented ossification located outside the fibrous ring of the intervertebral disc. In recent decades, the most widespread theory is that after inflammation in the area of attachment of the fibrous ring to the vertebral body, fatty degeneration occurs with reparative processes, as a result of which the growth of new bone – syndesmophyte – begins. It is believed that the likelihood of developing syndesmophyte is two to three times higher in the angles of those vertebrae in which active inflammation or fatty changes were detected on magnetic resonance tomography (MRI) in the previous 2 years, the latter having a stronger association with subsequent pathological bone formation. However, this relationship is ambiguous according to different studies.The aim – comparison of the exact localization of magnetic resonance tomography and computed tomography (CT) signs of lesions on the vertebral endplates, characteristic of axial spondyloarthritis, in patients with ankylosing spondylitis.Material and methods. The cross-sectional study included 10 patients with AS who met the inclusion criteria.All patients underwent a standard examination for AS, as well as MRI and CT examination of the lumbar spine.A special technique for joint assessment of changes detected during MRI and CT examination has been developed.For the primary analysis, changes found on the upper endplates of 5 lumbar vertebrae
Ankylosing spondylitis (AS) is a long-lasting autoimmune disorder marked by inflammatory processes affecting the spinal column and sacroiliac joints, alongside abnormal bone growth. This review aims to summarize the mechanisms underlying pathological new bone formation in AS, focusing on key cell types, molecular pathways, and their roles in disease progression. We will discuss the interplay between osteoblasts and osteoclasts, the cytokines and signaling pathways that influence new bone formation, and how recent research findings contribute to our understanding of this complex process. Through a comprehensive analysis of relevant literature, this review seeks to provide a theoretical foundation and direction for future therapeutic strategies.
The enthesopathy of ankylosing spondylitis.
The enthesopathic lesion of ankylosing spondylitis consists of a nonspecific, nongranulomatous inflammatory lesion which leads to destruction of the attachment of ligament to bone. Resulting erosion leads to reactive bone formation which may form a new enthesis and around the outer fibres of the annulus may lead to syndesmophyte formation. What determines the distribution of the enthesopathy and ankylosis is not known.
Published in British journal of rheumatology (1983)
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