Inhibition of CXCR4 inhibits the proliferation and osteogenic potential of fibroblasts from ankylosing spondylitis via the Wnt/β‑catenin pathway

He, C.; Da-he, LI; Gao, Jian‐Zhong; Li, Jia; Liu, Zhongtang; Xu, Weidong

doi:10.3892/mmr.2019.9980

Cited by 11 publications

(13 citation statements)

References 42 publications

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“…β-catenin is a critical protein in the classical Wnt signaling pathway that plays a central role in the formation of ectopic bone (10). Moreover, the production of β-catenin is positively associated with AS osteogenesis (60). The present study revealed that β-catenin levels were upregulated in the AS model (PG) and downregulated in the groups with a reduced mechanical load (PG + NLB and PG + PLB), which was consistent with previous studies (10).…”

Section: Discussionsupporting

confidence: 91%

Tail suspension delays ectopic ossification in proteoglycan‑induced ankylosing spondylitis in mice via miR‑103/DKK1

Zhang

Zeng

et al. 2021

Exp Ther Med

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Ankylosing spondylitis (AS), characterized by inflammatory lesions and osteophyte formation, is a common immune rheumatic disease affecting the sacroiliac and axial joints. A high-intensity mechanical load is known to accelerate the heterotopic ossification associated with enthesitis in AS. Thus, the present study explored whether decreased mechanical load could delay the heterotopic ossification in AS. First, 24-week-old female BALB/c mice were induced with proteoglycan (PG) to establish an AS model. The AS-induced pathological and bone morphological changes of the sacroiliac joint were confirmed by hematoxylin and eosin staining and microCT analysis, respectively. Subsequently, the mice were treated with interventions of different mechanical loads. Using reverse transcription-quantitative PCR, it was revealed that expression levels of the osteogenesis-related genes bone morphogenetic protein-2, runt-related transcription factor 2 and osteocalcin were significantly reduced in sacroiliac bone tissue after intervention with a reduced mechanical load. The level of mechanosensory microRNA (miR)-103 increased in response to reduced mechanical loads. Consistently, in groups with reduced mechanical load, proteins with mechanical functions, including ρ-associated coiled-coil-containing protein kinase 1 (ROCK1), phosphorylated (p)-Erk1/2 and β-catenin, were reduced compared with the PG control. A dual-luciferase assay verified that miR-103 binds to the 3'-untranslated region end of Rock1 mRNA, thus negatively regulating the activity of Rock1 and affecting pathological ossification during AS. However, immunohistochemical staining indicated that the expression of dickkopf Wnt signaling pathway inhibitor 1, an inhibitor of the Wnt/β-catenin pathway, was increased in sacroiliac tissues. The results indicated that tail suspension decreased the mechanical load, thus reducing the bone formation in AS mice. Furthermore, tail suspension could inhibit the activation of mechanical kinase ROCK1 and p-Erk1/2 in the MAPK signaling pathway by upregulating miR-103, thereby inhibiting the classical osteogenesis-related Wnt/β-catenin pathway in AS. In summary, the present study uncovered the ameliorative effect of suspension on AS and its therapeutic potential for AS.

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Section: Discussionsupporting

confidence: 91%

Tail suspension delays ectopic ossification in proteoglycan‑induced ankylosing spondylitis in mice via miR‑103/DKK1

Zhang

Zeng

et al. 2021

Exp Ther Med

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“…The expression of the CXCL12/CXCR4 axis was increasing in the patients with SCI and AS (Knerlich-Lukoschus et al, 2011;Tysseling et al, 2011). Besides, a study found that CXCR4 could accelerate the ossification of fibroblasts in patients with AS (He et al, 2019). FN1 (fibronectin 1) is involved in the process of cell adhesion and migration (Cai et al, 2018) and could rely on the TGF-β/PI3K/Akt pathway to promote chondrocyte differentiation and collagen production in fractured bones (Zhang et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Drug Discovery in Spinal Cord Injury With Ankylosing Spondylitis Identified by Text Mining and Biomedical Databases

Wang

et al. 2022

Front. Genet.

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Spinal cord injury (SCI) and ankylosing spondylitis (AS) are common inflammatory diseases in spine surgery. However, it is a project where the relationship between the two diseases is ambiguous and the efficiency of drug discovery is limited. Therefore, the study aimed to investigate new drug therapies for SCI and AS. First, text mining was used to obtain the interacting genes related to SCI and AS, and then, the functional analysis was conducted. Protein–protein interaction (PPI) networks were constructed by STRING online and Cytoscape software to identify hub genes. Last, hub genes and potential drugs were performed after undergoing drug–gene interaction analysis, and MicroRNA and transcription factors regulatory networks were also analyzed. Two hundred five genes common to “SCI” and “AS” identified by text mining were enriched in inflammatory responses. PPI network analysis showed that 30 genes constructed two significant modules. Ultimately, nine (SST, VWF, IL1B, IL6, CXCR4, VEGFA, SERPINE1, FN1, and PROS1) out of 30 genes could be targetable by a total of 13 drugs. In conclusion, the novel core genes contribute to a novel insight for latent functional mechanisms and present potential prognostic indicators and therapeutic targets in SCI and AS.

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“…CXCR4 encodes a CXC chemokine receptor specific for stromal cell-derived factor-1 located on the cell surface, which acts with the CD4 protein to support HIV entry into cells; it is also highly expressed in breast cancer cells (36). He et al (37) discovered that inhibition of CXCR4 prevents the proliferation and osteogenic potential of fibroblasts from ankylosing spondylitis, indicating that CXCR4 may play a key role in the development and perpetuation of joint stiffness. Our results were consistent with these previous reports.…”

Section: Discussionmentioning

confidence: 99%

PDGFRB as a potential therapeutic target of ankylosing spondylitis: validation following bioinformatics analysis

Feng

Zhu

Yan

et al. 2020

Cell Mol Biol (Noisy-le-grand)

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Ankylosing spondylitis (AS) is a chronic, progressive, and inflammatory disease that mainly affects the central axis joint. Although this disease has already been well documented and studied, its pathogenesis is still not well understood. This study aimed to screen and identify key candidate genes involved in the progression of AS. For this purpose, expression profiles of GSE39340 and GSE41038 were downloaded from the Gene Expression Omnibus and displayed in the form of volcano plots and heatmaps. Differentially expressed genes (DEGs) were identified by the Limma package in R and functional enrichment analyses were performed. Moreover, STRING and Cytoscape were utilized to construct protein-protein interaction (PPI) networks and screen significant modules. Immunohistochemistry (IHC) in tissue chips of AS and normal human synovial tissues was performed to confirm the major proteins associated with its development. Western blotting (WB) and alizarin red staining were applied to validate the expression level of platelet-derived growth factor receptor beta (PDGFRB) and function during osteogenesis differentiation of fibroblasts in AS. A total of 256 DEGs were screened, including 191 up-regulated genes and 65 down-regulated genes. The enriched functions of these identified genes mainly included adherens junction, focal adhesion, and cell-substrate adherens junction. The pathways most highly associated with the progression of AS were TGF-β signaling pathway, the Hippo signaling pathway, and the AGE-RAGE signaling pathway. In addition, IHC showed that mitogen-activated protein kinase 1 (MAPK1), C-X-C motif chemokine receptor 4 (CXCR4), and PDGFRB were highly expressed in AS. PDGFRB was found upregulated during osteogenesis of fibroblasts and stimulates osteogenesis in AS. These findings may improve our understanding of the molecular mechanisms controlling AS. Pharmacological targeting of PDGFRB may initiate a possible suppression of bone formation in AS.

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Inhibition of CXCR4 inhibits the proliferation and osteogenic potential of fibroblasts from ankylosing spondylitis via the Wnt/β‑catenin pathway

Cited by 11 publications

References 42 publications

Tail suspension delays ectopic ossification in proteoglycan‑induced ankylosing spondylitis in mice via miR‑103/DKK1

Tail suspension delays ectopic ossification in proteoglycan‑induced ankylosing spondylitis in mice via miR‑103/DKK1

Drug Discovery in Spinal Cord Injury With Ankylosing Spondylitis Identified by Text Mining and Biomedical Databases

PDGFRB as a potential therapeutic target of ankylosing spondylitis: validation following bioinformatics analysis

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