Wnt/β‐catenin signaling plays a key role in the development of spondyloarthritis

Xie, Wei‐Fen; Zhou, Lijiang; Li, Shan; Hui, Tianqian; Chen, Di

doi:10.1111/nyas.12968

Cited by 57 publications

(36 citation statements)

References 74 publications

(151 reference statements)

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“…It is well known that the pathogenesis of AS is characterized by three phases: inflammation, erosion and abnormal bone outgrowth [32]. In this regard our data seem to recapitulate all these pathogenetic stages, showing deregulation of genes involved in the inflammatory process as well of transcripts that play a role in bone remodeling (i.e., bone growth and bone erosion).…”

Section: Discussionsupporting

confidence: 73%

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Gene Expression Analysis before and after Treatment with Adalimumab in Patients with Ankylosing Spondylitis Identifies Molecular Pathways Associated with Response to Therapy

Dolcino

Tinazzi

Pelosi

et al. 2017

Genes

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The etiology of Ankylosing spondylitis (AS) is still unknown and the identification of the involved molecular pathogenetic pathways is a current challenge in the study of the disease. Adalimumab (ADA), an anti-tumor necrosis factor (TNF)-alpha agent, is used in the treatment of AS. We aimed at identifying pathogenetic pathways modified by ADA in patients with a good response to the treatment. Gene expression analysis of Peripheral Blood Cells (PBC) from six responders and four not responder patients was performed before and after treatment. Differentially expressed genes (DEGs) were submitted to functional enrichment analysis and network analysis, followed by modules selection. Most of the DEGs were involved in signaling pathways and in immune response. We identified three modules that were mostly impacted by ADA therapy and included genes involved in mitogen activated protein (MAP) kinase, wingless related integration site (Wnt), fibroblast growth factor (FGF) receptor, and Toll-like receptor (TCR) signaling. A separate analysis showed that a higher percentage of DEGs was modified by ADA in responders (44%) compared to non-responders (12%). Moreover, only in the responder group, TNF, Wnt, TLRs and type I interferon signaling were corrected by the treatment. We hypothesize that these pathways are strongly associated to AS pathogenesis and that they might be considered as possible targets of new drugs in the treatment of AS.

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Section: Discussionsupporting

confidence: 73%

“…Moreover, it has been recently suggested that Wnt signaling may take part to the process of ankylosis in spondyloarthritis [32]. …”

Section: Discussionmentioning

confidence: 99%

Gene Expression Analysis before and after Treatment with Adalimumab in Patients with Ankylosing Spondylitis Identifies Molecular Pathways Associated with Response to Therapy

Dolcino

Tinazzi

Pelosi

et al. 2017

Genes

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“…Dkk1 heterozygous KO mice showed a high bone mass phenotype [44], and Dkk1 -overexpressing transgenic mice had a low bone mass phenotype [45]. In addition, severe destruction in spine tissues was observed in 3- and 6-month old β-catenin ( ex3 ) Col2CreER mice, including progressive loss of growth plate and endplate cartilage, disorganized annulus fibrosus and nucleus pulposus tissues, and increased osteophyte formation in the disc of the entire spine [34••, 46••]. These studies suggest that the activation of β-catenin signaling may contribute to the development and progression of SpA.…”

Section: Wnt/β-catenin Signaling In Spamentioning

confidence: 99%

Wnt/β-catenin Signaling in Osteoarthritis and in Other Forms of Arthritis

et al. 2017

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Purpose of Review Arthritis defines a large group of diseases primarily affecting the joint. It is the leading cause of pain and disability in adults. Osteoarthritis (OA) affecting the knee or hip is the most common form among over 100 types of arthritis. Other types of arthritis include erosive hand OA, tempo-romandibular joint (TMJ) OA, facet joint OA, diffuse idiopathic skeletal hyperostosis (DISH), and spondyloarthritis (SpA). However, the specific molecular signals involved in the development and progression of OA and related forms of arthritis remain largely unknown. The canonical wingless/integrated (Wnt)/β-catenin signaling pathway could play a unique role in the pathogenesis of arthritis. In this review article, we will focus on the molecular mechanisms of Wnt/β-catenin signaling in the pathogenesis of OA and other types of arthritis. Recent Findings Emerging evidence demonstrates that Wnts and Wnt-related molecules are involved in arthritis development and progression in human genetic studies and in vitro studies. Also, mouse models have been generated to determine the role of Wnt/β-catenin signaling in the pathogenesis of arthritis. Summary Wnt/β-catenin signaling represents a unique signaling pathway regulating arthritis development and progression, and the molecules in this particular pathway may serve as targets for the therapeutic intervention of arthritis. Mediators and downstream effectors of Wnt/β-catenin signaling are increased in OA as well other forms of arthritis, including DISH and SpA. Through extensive investigations, including pre-clinical studies in transgenic mice and translational and human studies, the Wnt/β-catenin signaling pathway has been proven to play roles in bone and joint pathology by directly affecting bone, cartilage, and synovial tissue; further, these pathologies can be reduced through targeting this pathway. Continued investigation into the distinct molecular signaling of the Wnt/β-catenin pathway will provide additional insights toward the therapeutic intervention in arthritis.

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“…In addition to its dispensable roles in the development of T cells and the immune system, mounting evidence has recently suggested that it is involved in the pathogenesis of many types of autoimmune diseases, including rheumatoid arthritis (RA), SLE, spondyloarthritis (PsA), and ankylosing spondylitis (AS) [12–17]. In SLE patients, aberrant Wnt/ β -catenin signaling was observed in both peripheral B and T cell fractions [18].…”

Section: Introductionmentioning

confidence: 99%

Dickkopf-1 Is a Biomarker for Systemic Lupus Erythematosus and Active Lupus Nephritis

Xue

Yang

et al. 2017

Journal of Immunology Research

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An early diagnosis of lupus nephritis (LN) has an important clinical implication in guiding treatments of systemic lupus erythematosus (SLE) in clinical settings. In this study, the concentrations of Wnt-3A, Frizzled-8 (FZD-8), and Dickkopf-1 (DKK-1) of Wnt signaling, as well as their diagnostic values for accessing LN, were evaluated by ELISA in sera and urine of 111 SLE patients (31 with LN and 80 without LN) and 70 healthy cohorts. Significantly more abundances of DKK-1 protein were determined in both of sera and urine of SLE patients compared to healthy cohorts (p < 0.0001); in particular the serum DKK-1 concentration was even higher in LN-SLE patients relative to non-LN SLE subjects (p < 0.0001). Intriguingly, concentrations of above examined proteins in SLE patients showed no correlation between serum and urine. Moreover, a combination of DKK-1 with anti-dsDNA and/or levels of complement C3 and C4 could not increase the specificity and/or sensitivity for identification of patients with LN diseases, but both ROC curve and multiple-factor nonconditional logistic regression analysis showed that serum DKK-1 was considered better positive biomarker for identification of LN in SLE patients. These results imply that serum and/or urine DKK-1 may be a valuable and independent biomarker for identification of SLE patients with LN.

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Wnt/β‐catenin signaling plays a key role in the development of spondyloarthritis

Cited by 57 publications

References 74 publications

Gene Expression Analysis before and after Treatment with Adalimumab in Patients with Ankylosing Spondylitis Identifies Molecular Pathways Associated with Response to Therapy

Gene Expression Analysis before and after Treatment with Adalimumab in Patients with Ankylosing Spondylitis Identifies Molecular Pathways Associated with Response to Therapy

Wnt/β-catenin Signaling in Osteoarthritis and in Other Forms of Arthritis

Dickkopf-1 Is a Biomarker for Systemic Lupus Erythematosus and Active Lupus Nephritis

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