Inverse Agonist of Retinoid-Related Orphan Receptor-Alpha Prevents Apoptosis and Degeneration in Nucleus Pulposus Cells via Upregulation of YAP

Liang, Tongzhou; Qiu, Jincheng; Li, Shaoguang; Deng, Zhihuai; Qiu, Xianjian; Hu, Wenjun; Li, Pengfei; Chen, Taiqiu; Liang, Zhancheng; Zhou, Hang; Gao, Bo; Huang, Dongsheng; Liang, Anjing; Gao, Wenjie

doi:10.1155/2021/9954909

Cited by 6 publications

(5 citation statements)

References 43 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The homozygous (sg/sg) mice exhibit cerebellar ataxia, bone mineral content loss, and osteopenic phenotype [8,9]. Our studies suggested RORα regulates nucleus pulposus matrix metabolism and apoptosis [10]. Moreover, RORα contributes to chondrocyte hypertrophy during the development of endochondral bone and growth plates, acting as a prehypertrophic marker [11,12].…”

Section: Introductionmentioning

confidence: 75%

Inhibition of nuclear receptor RORα attenuates cartilage damage in osteoarthritis by modulating IL-6/STAT3 pathway

et al. 2021

Self Cite

View full text Add to dashboard Cite

Osteoarthritis (OA) is characterized by cartilage destruction, chronic inflammation, and local pain. Evidence showed that retinoic acid receptor-related orphan receptor-α (RORα) is crucial in cartilage development and OA pathogenesis. Here, we investigated the role and molecular mechanism of RORα, an important member of the nuclear receptor family, in regulating the development of OA pathologic features. Investigation into clinical cartilage specimens showed that RORα expression level is positively correlated with the severity of OA and cartilage damage. In an in vivo OA model induced by anterior crucial ligament transaction, intra-articular injection of si-Rora adenovirus reversed the cartilage damage. The expression of cartilage matrix components type II collagen and aggrecan were elevated upon RORα blockade. RNA-seq data suggested that the IL-6/STAT3 pathway is significantly downregulated, manifesting the reduced expression level of both IL-6 and phosphorylated STAT3. RORα exerted its effect on IL-6/STAT3 signaling in two different ways, including interaction with STAT3 and IL-6 promoter. Taken together, our findings indicated the pivotal role of the RORα/IL-6/STAT3 axis in OA progression and confirmed that RORα blockade improved the matrix catabolism in OA chondrocytes. These results may provide a potential treatment target in OA therapy.

show abstract

Section: Introductionmentioning

confidence: 75%

Inhibition of nuclear receptor RORα attenuates cartilage damage in osteoarthritis by modulating IL-6/STAT3 pathway

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Ample studies have shown that the Hippo signaling pathway is related closely to mechanical stress and is involved in bone and cartilage degenerative diseases [ 42 , 43 ]. According to the available evidence, the YAP protein has been reported to promote the anabolic metabolism of ECM in NPCs [ 31 , 32 ]. CTGF, as the target molecule of the Hippo signaling pathway, has been reported to be involved in the ECM metabolism of nucleus pulposus cells [ 31 , 32 ].…”

Section: Discussionmentioning

confidence: 99%

“…According to the available evidence, the YAP protein has been reported to promote the anabolic metabolism of ECM in NPCs [ 31 , 32 ]. CTGF, as the target molecule of the Hippo signaling pathway, has been reported to be involved in the ECM metabolism of nucleus pulposus cells [ 31 , 32 ]. Nevertheless, the mechanisms governing LATS/YAP/CTGF in the regulation of NPCs have remained elusive.…”

Section: Discussionmentioning

confidence: 99%

“…As reported, the key effector, the yes-associated protein (YAP), was downregulated, while the phosphorylated YAP protein was upregulated in degenerative NP tissues [ 30 ]. Recently, it has been reported that YAP mediates the unbalanced ECM metabolism in NPCs and is found to be regulative in the progression of IDD [ 31 , 32 ]. As the target gene of YAP, the connective tissue growth factor (CTGF), also known as CCN2, is a secreted peptide consisting of 349 amino acids, composed of N-terminal signal peptide, intermediate protein-binding domain, and C-terminal-binding domain [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Irisin Ameliorates Intervertebral Disc Degeneration by Activating LATS/YAP/CTGF Signaling

Chen

Lin

et al. 2022

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

Unbalanced metabolism of an extracellular matrix (ECM) in nucleus pulposus cells (NPCs) is widely acknowledged as the primary cause of intervertebral disc degeneration (IDD). Irisin, a novel myokine, is cleaved from fibronectin type III domain-containing 5 (FNDC5) and has recently been proven to regulate the metabolism of ECM. However, little is known about its potential on NPCs and the development of IDD. Therefore, this study sought to examine the protective effects and molecular mechanism of irisin on IDD in vivo and in vitro. Decreased expression levels of FNDC5 and anabolism markers (COL2A1 and ACAN) but increased levels of catabolism markers (ADAMTS4) were found in degenerative nucleus pulposus (NP) tissues. In a punctured-induced rat IDD model, irisin treatment was found to significantly slow the development of IDD, and in TNF-α-stimulated NPCs, irisin treatment partly reversed the disorder of ECM metabolism. In mechanism, RNA-seq results suggested that irisin treatment affected the Hippo signaling pathway. Further studies revealed that with irisin treatment, the phosphorylation levels of key factors (LATS and YAP) were downregulated, while the expression level of CTGF was upregulated. Moreover, CTGF knockdown partially eliminated the protective effects of irisin on the metabolism of ECM in NPCs, including inhibiting the anabolism and promoting the catabolism. Taken together, this study demonstrated that the expression levels of FNDC5 were decreased in degenerative NP tissues, while irisin treatment promoted the anabolism, inhibited the catabolism of the ECM in NPCs, and delayed the progression of IDD via LATS/YAP/CTGF signaling. These results shed light on the protective actions of irisin on NPCs, leading to the development of a novel therapeutic target for treating IDD.

show abstract

“…Interestingly, nucleus pulposus cells have recently been extensively investigated in LBP-W given their roles in IVD inflammation and degeneration. [50][51][52] The current bibliometric analysis identifies several research priorities. First, as a prevalent and disabling back condition, lumbar spinal stenosis (LSS) was one of the emerging trends in LBP-O research.…”

mentioning

confidence: 99%

Trends of Low Back Pain Research in Older and Working-Age Adults from 1993 to 2023: A Bibliometric Analysis

Zheng,

Kawchuk,

Bussières

et al. 2023

JPR

View full text Add to dashboard Cite

Although the number of publications focusing on low back pain in older adults (LBP-O) and working-age adults (LBP-W) has been growing for decades, comparative research trends in these two populations, which may help to guide future investigation, have not been rigorously explored. This analysis aimed to describe publication patterns and trends of research targeting LBP-O and LBP-W over the last three decades. Peer-reviewed LBP-O and LBP-W articles published between 1993 and 2023 were retrieved from the Web of Science, which provided the details of annual publication volume, and prominent journals/countries/institutions. The relationship between the annual publication volumes and years was analyzed by Spearman correlation analysis. The hot topics and emerging trends were analyzed by VOSviewer and CiteSpace, respectively. A total of 4217 LBP-O-related and 50,559 LBP-W-related documents were included. The annual publication volumes of LBP-O and LBP-W articles increased over the years (r=0.995 to 0.998, p<0.001). The United States had the highest number of prominent institutions publishing relevant articles. The most prolific journal for LBP-O (5.4%) and LBP-W-related (6.1%) papers is the journal "Spine". Cognitive behavioral therapy, intervertebral disc (IVD) degeneration, physiotherapy, physical activity, and walking were the recent hot topics and physical activity was an emerging trend in LBP-O, while surgery and IVD degeneration (also a hot topic) were emerging trends in LBP-W. This study highlights the paucity of LBP-O-related research in the past. The United States and the journal Spine stand out in LBP research. The research trend of physical activity in LBP-O is consistent with the recognized importance of physical activity for older adults in general, and for managing LBP-O in particular. Conversely, the emerging trends of surgery and intervertebral disc degeneration in LBP-W research highlight a focus on the biomedical model of LBP despite LBP being a biopsychosocial condition.

show abstract

Inverse Agonist of Retinoid-Related Orphan Receptor-Alpha Prevents Apoptosis and Degeneration in Nucleus Pulposus Cells via Upregulation of YAP

Cited by 6 publications

References 43 publications

Inhibition of nuclear receptor RORα attenuates cartilage damage in osteoarthritis by modulating IL-6/STAT3 pathway

Inhibition of nuclear receptor RORα attenuates cartilage damage in osteoarthritis by modulating IL-6/STAT3 pathway

Irisin Ameliorates Intervertebral Disc Degeneration by Activating LATS/YAP/CTGF Signaling

Trends of Low Back Pain Research in Older and Working-Age Adults from 1993 to 2023: A Bibliometric Analysis

Contact Info

Product

Resources

About