No evidence for a direct role of HLA-B27 in pathological bone formation in axial SpA

Neerinckx, Barbara; Kollnberger, Simon; Shaw, Jacqueline; Lories, Rik

doi:10.1136/rmdopen-2017-000451

Cited by 13 publications

(7 citation statements)

References 29 publications

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“…Contrary to the previously discussed literature, a study argues against a direct role of HLA-B27 in mediating new bone formation in axial SpA ( 106 ). HLA-B27 overexpression in various in vitro mouse and human differentiation systems mimicking endochondral ossification did not result in differences in bone formation when compared to the HLA-B7 overexpression controls.…”

Section: Hla-b27 In New Bone Formation: a Predisposing Factor?contrasting

confidence: 80%

Juvenile Spondyloarthritis: What More Do We Know About HLA-B27, Enthesitis, and New Bone Formation?

Yeo

Leong

et al. 2021

Front. Med.

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Juvenile spondyloarthritis (JSpA) refers to a diverse spectrum of immune-mediated inflammatory arthritides whose onset occurs in late childhood and adolescence. Like its adult counterpart, JSpA is typified by a strong association with human leukocyte antigen-B27 (HLA-B27) and potential axial involvement, while lacking rheumatoid factor (RF) and distinguishing autoantibodies. A characteristic manifestation of JSpA is enthesitis (inflammation of insertion sites of tendons, ligaments, joint capsules or fascia to bone), which is commonly accompanied by bone resorption and new bone formation at affected sites. In this Review, advances in the role of HLA-B27, enthesitis and its associated osteoproliferation in JSpA pathophysiology and treatment options will be discussed. A deeper appreciation of how these elements contribute to the JSpA disease mechanism will better inform diagnosis, prognosis and therapy, which in turn translates to an improved quality of life for patients.

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Section: Hla-b27 In New Bone Formation: a Predisposing Factor?contrasting

confidence: 80%

Juvenile Spondyloarthritis: What More Do We Know About HLA-B27, Enthesitis, and New Bone Formation?

Yeo

Leong

et al. 2021

Front. Med.

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“…ATDC5 cells can differentiate into chondrocytes. In addition, ATDC5 cells are widely used in the study of AS ( 23 , 24 ). LPS is commonly used as an inducer of inflammatory responses, stimulating cells to induce inflammatory responses and produce proinflammatory cytokines ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

KLF4 downregulates FGF21 to activate inflammatory injury and oxidative stress of LPS‑induced ATDC5 cells via SIRT1/NF‑κB/p53 signaling

et al. 2022

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Ankylosing spondylitis (AS) is a chronic inflammatory disease. Transcriptional regulation of fibroblast growth factor 21 (FGF21) by the transcription factor Krüppel-like factor 4 (KLF4) serves an important role in chronic inflammatory disease. However, to the best of our knowledge, the role of both these factors in AS has not been previously reported. In the present study, ATDC5 cells were induced by lipopolysaccharide (LPS) to establish an AS inflammatory injury model. The expression levels of FGF21 and KLF4 were detected using reverse transcription-quantitative PCR and western blotting. Cell transfection was performed to alter the expression levels of KLF4 and FGF21. Subsequently, the regulatory effects and mechanisms underlying KLF4 and FGF21 on oxidative stress and inflammation in AS were investigated by performing Cell Counting Kit-8 assays, ELISAs, TUNEL staining and western blotting. Moreover, the expression levels of sirtuin 1 (SirT1)/nF-κB/p53 pathway-related proteins were detected via western blotting. FGF21 overexpression promoted LPS-induced viability on ATDC5 cells, inhibited lPS-induced apoptosis, and decreased the lPS-induced inflammatory response and oxidative stress levels of ATDC5 cells. Overexpression of the transcription factor KLF4 reversed the protective effect of FGF21 overexpression on LPS-induced inflammatory injury in ATDC5 cells. The results suggested that this process may be achieved via regulating the SirT1/nF-κB/p53 signaling pathway. Overall, the present study demonstrated that KLF4 downregulates FGF21 to activate inflammatory injury and oxidative stress of LPS-induced ATDC5 cells via SIRT1/NF-κB/p53 signaling.

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“…In SpA, inflammation of the sacroiliac and intervertebral joints is associated with both erosive bone changes and new bone formation at the entheses. HLA-B27 does not directly affect bone formation in transgenic mice or osteoblast differentiation by mouse or human bone precursor cells in vitro 80 ; rather, epigenetic and gene expression analyses suggest that new bone formation occurs in SpA owing to HLA-B27-driven inflammation 103,104 . The mechanistic hypotheses proposed to account for these findings are depicted in Fig.…”

Section: [H1] Mechanisms Of Hla Disease Associationsmentioning

confidence: 93%

HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications

2019

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Our understanding of the mechanisms underlying HLA associations with inflammatory arthritis continues to evolve. Disease associations have been refined, and interactions of HLA genotype with other genes and environmental risk factors in determining disease risk have been identified. This Review provides basic information on the genetics and molecular function of HLA molecules, as well as general features of HLA associations with disease. We summarise evidence for various peptidedependent and peptide-independent mechanisms by which HLA alleles might contribute to the pathogenesis of three types of inflammatory arthritis: rheumatoid arthritis, spondyloarthritis and systemic juvenile idiopathic arthritis. Also discussed are HLA allelic associations that shed light on the genetic heterogeneity of inflammatory arthritides and on the relationships between adult and pediatric forms of arthritis. Clinical implications range from improved diagnosis and outcome prediction to the possibility of using HLA associations in developing personalized strategies for the treatment and prevention of these diseases. [ED: Some general editorial comments are replied to in the marginal comments. For replies to reviewers, please see the accompanying file.]

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No evidence for a direct role of HLA-B27 in pathological bone formation in axial SpA

Cited by 13 publications

References 29 publications

Juvenile Spondyloarthritis: What More Do We Know About HLA-B27, Enthesitis, and New Bone Formation?

Juvenile Spondyloarthritis: What More Do We Know About HLA-B27, Enthesitis, and New Bone Formation?

KLF4 downregulates FGF21 to activate inflammatory injury and oxidative stress of LPS‑induced ATDC5 cells via SIRT1/NF‑κB/p53 signaling

HLA associations in inflammatory arthritis: emerging mechanisms and clinical implications

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