Paricalcitol inhibits the Wnt/beta-catenin signaling pathway and ameliorates  experimentally induced arthritis

Yolbaş, Servet; Yıldırım, Ahmet; Tektemur, Ahmet; Çelik, Zülfinaz Betül; Etem, Ebru Önalan; Özercan, İbrahim Hanifı; Akın, Mehmet; Koca, Süleyman Serdar

doi:10.3906/sag-1804-62

Cited by 7 publications

(6 citation statements)

References 32 publications

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“…39 Others have reported that the inhibition of the Wnt/b-catenin signaling pathway caused by paricalcitol can ameliorate RA. 40 In a previous study of osteosarcoma, the knockdown of HOTTIP was demonstrated similarly to suppress cell proliferation and promote cell apoptosis via inhibiting the Wnt/b-catenin signaling pathway. 41 Together with our results, it appears evident that HOTTIP can inhibit SFRP1 and activate the Wnt signaling pathway by mediating Dnmt3b, thereby upregulating the levels of inflammatory factors and RA marker genes.…”

Section: Discussionmentioning

confidence: 94%

RETRACTED: Silencing of Long Non-coding RNA HOTTIP Reduces Inflammation in Rheumatoid Arthritis by Demethylation of SFRP1

Tang

et al. 2020

Molecular Therapy - Nucleic Acids

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Accumulating evidence suggests long non-coding RNAs (lncRNAs) play crucial roles in the pathogenesis of rheumatoid arthritis (RA). Here, we aimed to define the role of HOXA transcript at the distal tip (HOTTIP) in RA pathogenesis in relation to SFRP1 methylation and Wnt signaling pathway. HOTTIP was found highly expressed, and SFRP1 was hypermethylated in RA synovial fibroblasts (RASFs). Next, gain-or lossof-function experiments were conducted in RASFs to explore the effects of HOTTIP on the biological behaviors of RASFs. Silencing of HOTTIP or overexpression of SFRP1 inhibited RASF proliferation, invasion, and migration, while enhancing apoptosis. The relationship among HOTTIP, SFRP1, and Dnmt3b was determined using methylation-specific PCR (MSP), bisulfite sequencing PCR (BSP), RNA pull-down, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (ChIP) assays. The regulatory mechanisms of HOTTIP/Dnmt3b/SFRP1 were explored by altering their expression in RASFs. It was noted that HOTTIP could induce SFRP1 promoter methylation through recruitment of Dnmt3b and activate the Wnt signaling pathway. Finally, a rat RA model was established in order to evaluate the in vivo effects of HOTTIP and SFRP1, which suggested that HOTTIP silencing or SFRP1 elevation inhibited the progression of RA in vivo. Our key findings demonstrate the anti-inflammatory ability of HOTTIP silencing in RA through SFRP1 promoter demethylation. These findings support HOTTIP as a candidate anti-arthritis target.

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Section: Discussionmentioning

confidence: 94%

RETRACTED: Silencing of Long Non-coding RNA HOTTIP Reduces Inflammation in Rheumatoid Arthritis by Demethylation of SFRP1

Tang

et al. 2020

Molecular Therapy - Nucleic Acids

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“…Considering the role of cellular immune function in RA patients and the differentiation of CD4 + T cells into Th17 cells for the development of RA, 14 , 24 , 26 the effects of the serum-derived exosomes of RA patients on CD4 + T cell proliferation, apoptosis, and Th17 differentiation were analyzed. The result indicated that serum-derived exosomes from RA patients promoted proliferation of CD4 + T cells ( Figure 2a ) and inhibited CD4 + T cell apoptosis in RA patients ( Figure 2b ).…”

Section: Resultsmentioning

confidence: 99%

“…25 Wnt/ β-catenin inhibition was shown to alleviate RA. 26 In light of previous studies, we determined the impact of serum-derived exosome containing NEAT1 in RA through regulation of the miR-144-3p/ROCK2/Wnt/β-catenin axis.…”

Section: Introductionmentioning

confidence: 99%

Serum-derived exosomes containing NEAT1 promote the occurrence of rheumatoid arthritis through regulation of miR-144-3p/ROCK2 axis

Liu

Jiang

et al. 2021

Therapeutic Advances in Chronic Disease

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Background: Evidence has demonstrated that non-coding RNAs (ncRNAs) could be delivered efficiently to recipient cells using exosomes as a carrier. Additionally, long ncRNA nuclear enriched abundant transcript 1 (NEAT1) is emerging as a vital regulatory molecule in the progression of rheumatoid arthritis (RA). The aim of this study was to identify the NEAT1/miR-144-3p/Rho-associated protein kinase 2 (ROCK2) functional network regulating the WNT signaling pathway in RA. Methods: In vivo, a collagen-induced arthritis (CIA) model was established to analyze the effects of blood exosomes on the incidence, clinical score, and bone degradation of RA. In vitro, the CD4+T cells were characterized by flow cytometry and the cell activities were analyzed in the presence of exosome treatment alone or in combination with altered expression of NEAT1, miR-144-3p or Rho-associated protein kinase 2 (ROCK2). The expression of NEAT1, miR-144-3p, ROCK2, and corresponding proteins in the WNT signaling pathway was detected by RT-qPCR and western blot techniques. The binding profile of NEAT1 to miR-144-3p was evaluated via a combination approach of luciferase activity assay, RNA immunoprecipitation, and RNA pull-down experiments. Results: Blood exosomes extracted from RA patients increased the incidence of RA and bone destruction significantly. Overexpression of NEAT1 or ROCK2 promoted immune cell (CD4+T cells) proliferation, Th17 cell differentiation, and cell migration in response to stimulus, whereas knockout of the NEAT1 gene induced the expression of miR-144-3p in CD4+T cells. ROCK2 exogenous expression inhibited the expression of miR-144-3p, inducing activation of the WNT signaling pathway. Conclusion: A novel regulatory pathway NEAT1/miR-144-3p/ROCK2/WNT in RA was investigated as a potential target for RA therapy.

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“…38 Paricalcitol, a synthetic analog of vitamin D, modulates the Wnt pathway by reducing expression of Axin2, Wnt5a , and DKK1. 39 Collagen-induced arthritis rats treated with paricalcitol once a day for 17 days via subcutaneous injection had less cartilage and subchondral bone destruction, reduced perisynovial inflammation, and significantly lower arthritis scores at 29 days compared with sham-injected arthritic rats. 39 Finally, the natural microbial extracellular heteropolysaccharide Xanthan gum inhibits the Wnt pathway by suppressing expression of downstream genes MMP13 and ADAMTS5.…”

Section: Preclinical Genetic Studiesmentioning

confidence: 91%

“…39 Collagen-induced arthritis rats treated with paricalcitol once a day for 17 days via subcutaneous injection had less cartilage and subchondral bone destruction, reduced perisynovial inflammation, and significantly lower arthritis scores at 29 days compared with sham-injected arthritic rats. 39 Finally, the natural microbial extracellular heteropolysaccharide Xanthan gum inhibits the Wnt pathway by suppressing expression of downstream genes MMP13 and ADAMTS5. 40 IA administration of Xanthan gum to DMM-induced OA rabbits once weekly for 5 weeks restored articular cartilage, significantly lowered OARSI scores, and reduced cartilage damage compared with saline-injected OA controls.…”

Section: Preclinical Genetic Studiesmentioning

confidence: 91%

Inhibition of Wnt pathway activity as a treatment approach for human osteoarthritis: a systematic review

Sayegh

Zgoda

Leite

et al. 2022

Journal of Cartilage & Joint Preservation

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Paricalcitol inhibits the Wnt/beta-catenin signaling pathway and ameliorates experimentally induced arthritis

Cited by 7 publications

References 32 publications

RETRACTED: Silencing of Long Non-coding RNA HOTTIP Reduces Inflammation in Rheumatoid Arthritis by Demethylation of SFRP1

RETRACTED: Silencing of Long Non-coding RNA HOTTIP Reduces Inflammation in Rheumatoid Arthritis by Demethylation of SFRP1

Serum-derived exosomes containing NEAT1 promote the occurrence of rheumatoid arthritis through regulation of miR-144-3p/ROCK2 axis

Inhibition of Wnt pathway activity as a treatment approach for human osteoarthritis: a systematic review

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