NEAT1/miR‐193a‐3p/SOX5 axis regulates cartilage matrix degradation in human osteoarthritis

Li, Feng; Li, Xiangyang; Yang, Yue; Sun, Zhibo; Deng, Shuang; Jiang, Zhongping; Wen, Lai; Wu, Fei

doi:10.1002/cbin.11291

Cited by 35 publications

(16 citation statements)

References 28 publications

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“…We found high correlation between osteoarthritis and sciatica, fibromyalgia, headaches, and other back pain phenotypes, where the highest correlation is with spine osteoarthritis (genetic correlation [rg] = 0.61, 0.87, 0.39, and 0.79, respectively). SOX5 , one of the new signals, has been previously reported to be upregulated in human osteoarthritis cartilage ( Liu et al., 2020 ) and has been associated with back pain and with lumbar intervertebral disc degeneration ( Suri et al., 2018 ). These findings are supported by animal model data, in which inactivation of SOX5 leads to defects in skeletogenesis such as in cartilage development, the notochord, and intervertebral discs in mice ( Smits and Lefebvre, 2003 ; Smits et al., 2001 ).…”

Section: Resultsmentioning

confidence: 99%

Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

Boer¹,

Hatzikotoulas²,

Southam³

et al. 2021

Cell

243

159

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Summary Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.

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Section: Resultsmentioning

confidence: 99%

Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

Boer¹,

Hatzikotoulas²,

Southam³

et al. 2021

Cell

243

159

View full text Add to dashboard Cite

show abstract

“…Sox5 is expressed in numerous human tissues, including the testis, liver, lung, fetal brain and heart (26). Liu et al (27) demonstrated that overexpression of Sox5 can promote inflammatory responses and reverse microRNA-193a-3p mimic-mediated decrease in chondrocyte apoptosis in human osteoarthritis. However, studies have demonstrated that inhibiting Sox5 can promote apoptosis in rheumatoid arthritis and lung cancer (24,25).…”

Section: Discussionmentioning

confidence: 99%

High expression levels and localization of Sox5 in dilated cardiomyopathy

et al. 2020

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dilated cardiomyopathy (dcM) is a disease that can lead to heart expansion and severe heart failure, but the specific pathogenesis remains unclear. Sox5 is a member of the Sox family with a key role in cardiac function. However, the role of Sox5 in DCM remains unclear. In the present study, wild-type mice were intraperitoneally injected with doxorubicin (dox) to induce dcM, and heart specimens from human patients with DCM were used to investigate the preliminary role of Sox5 in DCM. The present study demonstrated that, compared with control human hearts, the hearts of patients with DCM exhibited high expression levels of Sox5 and activation of the wnt/β-catenin pathway. This result was consistent with Dox-induced DCM in mice. Furthermore, in Dox-treated mice, apoptosis was activated during the development of DCM. Inflammation and collagen deposition also increased in DCM mice. The results of the present study indicate that Sox5 may be associated with the development of DCM. Sox5 may be a novel potential factor that regulates DCM.

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“…2 and S 3 ), indicating that miR-193b-3p not only reduces the production of inflammatory factors but also blocks the STAT3 and NF-κB pathways, which are two important pathways that affect the inflammatory response in psoriasis pathogenesis [ 36 , 37 ]. Interestingly, there is evidence showing that miR-193a-3p, which is a sister microRNA of miR-193b-3p and shares similar mature sequences as that of miR-193b-3p (Table S2 ), also plays crucial roles in regulating the cellular inflammation through downregulation of inflammatory factors, including IL-1β, TNF-α, and NF-κB [ 38 , 39 ]. In fact, our parallel experimental results confirmed that miR-193a-3p has functions similar to that of miR-193b-3p in HaCaT cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

MiR-193b-3p–ERBB4 axis regulates psoriasis pathogenesis via modulating cellular proliferation and inflammatory-mediator production of keratinocytes

et al. 2021

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Psoriasis is an auto-inflammatory skin disease characterized by abnormal activation of epidermal keratinocytes, aberrant neovascularization, and dysregulation of immune cells. MicroRNAs are small non-coding RNAs that mainly function in the post-transcriptional regulation of gene expression. Recently, accumulating evidence has demonstrated that expression of microRNAs is dysregulated in psoriasis patients and microRNAs play key roles in psoriasis pathogenesis. Downregulation of miR-193b-3p has been identified to be associated with psoriasis development. However, the precise functions and action mechanisms of miR-193b-3p in psoriasis pathogenesis remain unclear. In this study, we confirmed the downregulation of miR-193b-3p in psoriasis patients, psoriasis-like inflammatory cellular models, and an imiquimod (IMQ) -induced mouse model. A negative correlation was found between miR-193b-3p level and patient Psoriasis Area and Severity Index (PASI) score. Furthermore, miR-193b-3p suppressed proliferation, inflammatory-factor secretion, and the STAT3 and NF-κB signaling pathways in keratinocytes. Importantly, intradermal injection of agomiR-193b-3p blocked, whereas antagomiR-193b-3p augmented, the psoriasis-like inflammation in the IMQ-induced mouse model. Bioinformatics analysis and the dual-luciferase reporter assay showed that miR-193b-3p targets ERBB4 3ʹ untranslated region (UTR). In addition, ERBB4 induced proliferation, inflammatory-factor production, and the STAT3 and NF-κB pathways in keratinocytes. Most importantly, forced expression of ERBB4 could attenuate the effects of miR-193b-3p in keratinocytes, indicating that miR-193b-3p inhibits keratinocyte activation by directly targeting ERBB4. In conclusion, our findings demonstrated that the miR-193b-3p–ERBB4 axis underlies the hyperproliferation and aberrant inflammatory-factor secretion of psoriatic keratinocytes, providing a novel, microRNA-related causal mechanism and a potential therapeutic target in psoriasis.

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NEAT1/miR‐193a‐3p/SOX5 axis regulates cartilage matrix degradation in human osteoarthritis

Cited by 35 publications

References 28 publications

Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

High expression levels and localization of Sox5 in dilated cardiomyopathy

MiR-193b-3p–ERBB4 axis regulates psoriasis pathogenesis via modulating cellular proliferation and inflammatory-mediator production of keratinocytes

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