scholarly journals Baicalin Protects Human OA Chondrocytes Against IL-1β-Induced Apoptosis and ECM Degradation by Activating Autophagy via MiR-766-3p/AIFM1 Axis

2020 ◽  
Vol Volume 14 ◽  
pp. 2645-2655 ◽  
Author(s):  
Zhi Li ◽  
Jiangqi Cheng ◽  
Jiuxiang Liu
Keyword(s):  
Ecm Degradation ◽  
Oa Chondrocytes ◽  
Induced Apoptosis

A Purified Extract from Clematis mandshurica Prevents Adenoviral-TRAIL Induced Apoptosis on Rat Articular Chondrocytes

2008 ◽  
Vol 36 (02) ◽  
pp. 399-410 ◽  
Author(s):  
Sung Won Lee ◽  
Hye Jeong Lee ◽  
Jeong Bon Moon ◽  
Sun Mee Choi ◽  
Duk Kyu Kim ◽  
...  
Keyword(s):  
Therapeutic Strategy ◽  
Articular Chondrocytes ◽  
Down Regulation ◽  
Phosphorylated Akt ◽  
Oa Chondrocytes ◽  
Novel Strategy ◽  
Induced Apoptosis

Since TNF-related apoptosis inducing ligand (TRAIL) is one of several apoptotic stimuli on articular chondrocytes, the modulation of the mechanism mediated by TRAIL could be considered as a novel strategy for the treatment of osteoarthritis (OA). Previous studies demonstrated that Clematis mandshurica prevents staurosporin-induced apoptosis in articular chondrocytes. This study was undertaken to examine whether Clematis mandshurica could prevent TRAIL-induced apoptosis in articular chondrocytes. Our data show that Clematis mandshurica prevents adenoviral TRAIL (Ad-TRAIL)-induced apoptosis in primary cultured articular chondrocytes. Clematis mandshurica prevents Ad-TRAIL-induced down-regulation of 14-3-3 and phosphorylated Akt. In addition, Clematis mandshurica treatment prevents the Ad-TRAIL-induced reduction of the interactions between 14-3-3 with phospho-ser112-Bad and phospho-ser136-Bad, and BcL-xL with phospho-ser155-Bad. A better understanding of the mechanism underlying inhibition of apoptosis in OA chondrocytes by Clematis mandshurica might lead to the development of a new therapeutic strategy for OA.

scholarly journals Chondrocyte Targeting Gold Nanoparticles Protect Growth Plate Against Inflammatory Damage By Maintaining Cartilage Balance

2021 ◽  
Author(s):  
Xue Bai ◽  
Hongyan Sun ◽  
Lina Jia ◽  
Junjie Xu ◽  
Peng Zhang ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Growth Plate ◽  
Inflammatory Cytokines ◽  
Degradation Rate ◽  
Cartilage Destruction ◽  
Chondrocyte Apoptosis ◽  
Inflammatory Damage ◽  
Clinical Challenge ◽  
Ecm Degradation ◽  
Induced Apoptosis

Abstract Background: Cartilage destruction caused by inflammation is a clinical challenge. Many studies have investigated cartilage destruction in adults, but little research was conducted on children. Results: The gaps without chondrocytes and ECM between the proliferative and hypertrophy zones of the GP cartilage were formation after the treatment of LPS, but the gaps were not observed in the AuNPs + LPS group. This finding can be attributed to the capability of AuNPs to target to the chondrocytes and reduce the release of inflammatory cytokines and secretion of ECM degradation factors induced by LPS. And then, the LPS-induced apoptosis rate of mouse chondrocytes and ECM degradation rate were inhibited. Finally, the balance of catabolic and anabolic factors in the ECM was maintained.Conclusion: These findings indicate that AuNPs can partially protect the cartilage of children from inflammatory damage by suppressing chondrocyte apoptosis and ECM degradation.

scholarly journals Mangiferin Prevents TBHP-Induced Apoptosis and ECM Degradation in Mouse Osteoarthritic Chondrocytes via Restoring Autophagy and Ameliorates Murine Osteoarthritis

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Yao Li ◽  
Yaosen Wu ◽  
Kaixia Jiang ◽  
Wen Han ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Protective Effect ◽  
Chondrocyte Apoptosis ◽  
Protective Effects ◽  
Ampk Signaling ◽  
Age Related ◽  
Osteoarthritic Chondrocytes ◽  
Ecm Degradation ◽  
Induced Apoptosis ◽  
Amp Activated Protein Kinase

Osteoarthritis (OA) is an age-related degenerative disease with complicated pathology involving chondrocyte apoptosis and extracellular matrix (ECM) degradation. Previous studies have shown that moderate autophagy has a protective effect against apoptosis in chondrocyte. Mangiferin is a natural polyphenol and exerts multiple pharmacological effects on different diseases in various preclinical studies. In this study, we investigated the effects of mangiferin on OA and delineated a potential molecular mechanism. In vitro, mangiferin treatment inhibited the expression of proapoptotic proteins induced by tert-butyl hydroperoxide (TBHP), increased the expression of antiapoptotic Bcl-2, and prevented ECM degradation by inhibiting the production of matrix-degrading enzyme. Mechanistically, mangiferin enhanced autophagy by activating the AMP-activated protein kinase (AMPK) signaling pathway. On the contrary, inhibition of autophagy partly abolished the protective effects of mangiferin on antiapoptosis and ECM synthesis in TBHP-treated chondrocyte. Correspondingly, the protective effect of mangiferin was also found in a mouse OA model. In conclusion, our results suggested that mangiferin serves as a potentially applicable candidate for treating OA.

scholarly journals AntimiR-30b Inhibits TNF-α Mediated Apoptosis and Attenuated Cartilage Degradation through Enhancing Autophagy

2016 ◽  
Vol 40 (5) ◽  
pp. 883-894 ◽  
Author(s):  
Zhe Chen ◽  
Tao Jin ◽  
Yong Lu
Keyword(s):  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Direct Interaction ◽  
Cartilage Degradation ◽  
Protective Role ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Tnf Α ◽  
Ecm Degradation ◽  
Induced Apoptosis

Objective: Cell death plays an important role in the pathology associated with inflammatory diseases such as osteoarthritis. It has been reported that autophagy can protect cells against tumour necrosis factor-α (TNF-α)-induced apoptosis. This study aimed to determine the potential role of microRNA-30b (miR-30b) in TNF-α-induced apoptosis, autophagy and differentiation in the chondrogenic ADTC5 cell line. Methods: To analyse the effect of TNF-α on the viability of ADTC5 cells, cell counting kit-8 and Hoechst 33342 staining were employed and the expression levels of caspase-3 and -9 were assessed. Autophagy was examined by analysing the levels of LC3B-II and p62 and quantitating GFP-LC3B by fluorescence microscopy. A luciferase reporter assay investigated the putative binding sites of miR-30b. The effects of miR-30b and antimiR-30b on autophagy, apoptosis and osteogenic differentiation of TNF-α-treated cells were determined by autophagosome, apoptosis and alkaline phosphatase assays, respectively. Results: TNF-α exposure decreased cell viability, increased apoptosis and positively regulated autophagy in ADTC5 cells. A direct interaction was detected between miR-30b and the mRNA 3ʹ-UTRs of autophagy genes BECN1 and ATG5. Overexpression of miR-30b downregulated autophagy genes and upregulated pro-apoptotic gene expression in TNF-α-treated cells, while treatment with antimiR-30b had the inverse effect. Overexpression of miR-30b also downregulated ECM degradation and anti-miR-30b reverse TNF-α-induced ECM degradation. Conclusions: Anti-miR-30b enhanced autophagy and attenuated cartilage degradation and played a protective role in TNF-α-induced apoptosis of ATDC5 cells. Anti-miR-30b may therefore elevate cellular survival during inflammation and has therapeutic potential for inflammatory diseases such as osteoarthritis.

scholarly journals Apigenin Alleviates Intervertebral Disc Degeneration via Restoring Autophagy Flux in Nucleus Pulposus Cells

2022 ◽  
Vol 9 ◽  
Author(s):  
Chenglong Xie ◽  
Yifeng Shi ◽  
Zuoxi Chen ◽  
Xin Zhou ◽  
Peng Luo ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Nuclear Translocation ◽  
Autophagic Flux ◽  
Ecm Degradation ◽  
Induced Apoptosis

Oxidative stress–induced apoptosis and senescence of nucleus pulposus (NP) cells play a crucial role in the progression of intervertebral disc degeneration (IVDD). Accumulation of studies has shown that activated autophagy and enhanced autophagic flux can alleviate IVDD. In this study, we explored the effects of apigenin on IVDD in vitro and in vivo. Apigenin was found to inhibit tert-butyl hydroperoxide (TBHP)–induced apoptosis, senescence, and ECM degradation in NP cells. In addition, apigenin treatment can restore the autophagic flux blockage caused by TBHP. Mechanistically, we found that TBHP may induce autophagosome and lysosome fusion interruption and lysosomal dysfunction, while apigenin alleviates these phenomena by promoting the nuclear translocation of TFEB via the AMPK/mTOR signaling pathway. Furthermore, apigenin also exerts a protective effect against the progression of IVDD in the puncture-induced rat model. Taken together, these findings indicate that apigenin protects NP cells against TBHP-induced apoptosis, senescence, and ECM degradation via restoration of autophagic flux in vitro, and it also ameliorates IVDD progression in rats in vivo, demonstrating its potential for serving as an effective therapeutic agent for IVDD.

scholarly journals Anisodamine Maintains the Stability of Intervertebral Disc Tissue by Inhibiting the Senescence of Nucleus Pulposus Cells and Degradation of Extracellular Matrix via Interleukin-6/Janus Kinases/Signal Transducer and Activator of Transcription 3 Pathway

2020 ◽  
Vol 11 ◽  
Author(s):  
Ning Tang ◽  
Yulei Dong ◽  
Chong Chen ◽  
Hong Zhao
Keyword(s):  
Intervertebral Disc ◽  
Nucleus Pulposus ◽  
Nuclear Translocation ◽  
Telomerase Activity ◽  
Nucleus Pulposus Cells ◽  
Stat3 Pathway ◽  
Stat3 Phosphorylation ◽  
Ecm Degradation ◽  
Collagen Ii ◽  
Induced Apoptosis

Objectives: Anisodamine (ANI) has been used to treat a variety of diseases. However, the study of ANI in intervertebral disc degeneration (IVDD) is unclear. This study investigated the effects of ANI on degenerative nucleus pulposus cells (NPCs) and IVDD rats, and its possible mechanisms.Methods: Human nucleus pulposus cells (HNPCs) were treated with IL-1β (20 ng/ml) to simulate IVDD, and an IVDD rat model was constructed. IL-1β-induced HNPCs were treated with different concentrations (10, 20, or 40 μM) of ANI, and IVDD rats were also treated with ANI (1 mg/kg).Results: ANI treatment significantly reduced the apoptosis, caspase-3 and SA-β-gal activities, and p53 and p21 proteins expression, while promoted telomerase activity and aggrecan and collagen II synthesis in IL-1β-induced HNPCs. Moreover, the introduction of ANI inhibited the expression of IL-6, phosphorylation of JAK and STAT3, and nuclear translocation of p-STAT3 in Degenerated HNPCs. Additionally, the application of ANI abolished the effects of IL-6 on apoptosis, SA-β-gal and telomerase activity, and the expression of p53, p21, aggrecan and collagen II proteins in degenerated HNPCs. Simultaneously, ANI treatment enhanced the effects of AG490 (inhibitor of JAK/STAT3 pathway) on IL-1β-induced apoptosis, senescence and ECM degradation in HNPCs. Furthermore, ANI treatment markedly inhibited the apoptosis and senescence in the nucleus pulposus of IVDD rats, while promoted the synthesis of aggrecan and collagen II. ANI treatment obviously inhibited JAK and STAT3 phosphorylation and inhibited nuclear translocation of p-STAT3 in IVDD rats.Conclusion: ANI inhibited the senescence and ECM degradation of NPCs by regulating the IL-6/JAK/STAT3 pathway to improve the function of NPCs in IVDD, which may provide new ideas for the treatment of IVDD.

scholarly journals Xanthohumol Inhibited Mechanical Stimulation-Induced Articular ECM Degradation by Mediating lncRNA GAS5/miR-27a Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Tiansheng Zheng ◽  
Qingluo Zhou ◽  
Jishang Huang ◽  
Jinliang Lai ◽  
Guanglin Ji ◽  
...  
Keyword(s):  
Mechanical Stimulation ◽  
Great Effort ◽  
Protective Effects ◽  
Joint Cartilage ◽  
Matrix Metalloproteinase 13 ◽  
Naturally Occurring ◽  
Potential Biomarker ◽  
Ecm Degradation ◽  
Oa Chondrocytes ◽  
Lncrna Gas5

Osteoarthritis (OA) is histopathologically marked by extracellular matrix (ECM) degradation in joint cartilage. Abnormal mechanical stimulation on joint cartilage may result in ECM degeneration and OA development. Matrix metalloproteinase 13 (MMP-13) is one of the catabolic enzymes contributing to the degradation of ECM, and it has become the potential biomarker for the therapeutic management of OA. Xanthohumol (XH), a naturally occurring prenylflavonoid derived from hops and beer, shows the protective activity against OA development. However, the potential mechanisms still need great effort. In this article, mechanical stimulation could significantly increase the expression of MMP-13 and lncRNA GAS5 (GAS5) and promoting ECM degradation. These could be effectively reversed by XH administration. Suppressed expression GAS5 ameliorated mechanical stimulation-induced MMP-13 expression. MiR-27a was predicted and verified as a target of GAS5, and overexpression of miR-27a down regulated the expression of MMP-13. Collectively, XH exhibited protective effects against mechanical stimulation-induced ECM degradation by mediating the GAS5/miR-27a signaling pathway in OA chondrocytes.

scholarly journals A Complex Relationship between Visfatin and Resistin and microRNA: An In Vitro Study on Human Chondrocyte Cultures

2018 ◽  
Vol 19 (12) ◽  
pp. 3909 ◽  
Author(s):  
Sara Cheleschi ◽  
Nicola Giordano ◽  
Nila Volpi ◽  
Sara Tenti ◽  
Ines Gallo ◽  
...  
Keyword(s):  
Collagen Type ◽  
In Vitro Study ◽  
Complex Relationship ◽  
Type Ii ◽  
Qrt Pcr ◽  
Chondrocyte Cultures ◽  
Oa Chondrocytes ◽  
Induced Apoptosis

Growing evidence indicates the important role of adipokines and microRNA (miRNA) in osteoarthritis (OA) pathogenesis. The purpose of the present study was to investigate the effect of visfatin and resistin on some miRNA (34a, 140, 146a, 155, 181a, let-7e), metalloproteinases (MMPs), and collagen type II alpha 1 chain (Col2a1) in human OA chondrocytes and in the T/C-28a2 cell line. The implication of nuclear factor (NF)-κB in response to adipokines was also assessed. Chondrocytes were stimulated with visfatin (5 or 10 μg/mL) and resistin (50 or 100 ng/mL) with or without NF-κB inhibitor (BAY-11-7082, 1 μM) for 24 h. Viability and apoptosis were detected by MMT and cytometry, miRNA, MMP-1, MMP-13, and Col2a1 by qRT-PCR and NF-κB activation by immunofluorescence. Visfatin and resistin significantly reduced viability, induced apoptosis, increased miR-34a, miR-155, miR-181a, and miR-let7e, and reduced miR-140 and miR-146a gene expression in OA chondrocytes. MMP-1, MMP-13, and Col2a1 were significantly modulated by treatment of OA chondrocytes with adipokines. Visfatin and resistin significantly increased NF-κB activation, while the co-treatment with BAY11-7082 did not change MMPs or Col2a1 levels beyond that caused by single treatment. Visfatin and resistin regulate the expression levels of some miRNA involved in OA pathogenesis and exert catabolic functions in chondrocytes via the NF-κB pathway. These data confirm the complex relationship between adipokines and miRNA.

scholarly journals Circular RNA circ_0128846 promotes the progression of osteoarthritis by regulating miR-127-5p/NAMPT axis

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Chao Liu ◽  
Ping Cheng ◽  
Jianjun Liang ◽  
Xiaoming Zhao ◽  
Wei Du
Keyword(s):  
Western Blot ◽  
Cell Viability ◽  
Circular Rna ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Circular Rnas ◽  
Western Blot Assay ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Ecm Degradation ◽  
Oa Chondrocytes

Abstract Background Mounting evidence indicates that circular RNAs (circRNAs) participate in the occurrence and development of various diseases, including osteoarthritis (OA). However, the effects and molecular mechanism of circ_0128846 in OA have not been reported. Methods The expression levels of circ_0128846, microRNA-127-5p (miR-127-5p), and nicotinamide phosphoribosyltransferase (NAMPT) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell viability was determined by Cell Counting Kit-8 (CCK-8) assay. Cell apoptosis was examined by flow cytometry and western blot assay. Inflammatory response and cartilage extracellular matrix (ECM) degradation were evaluated by western blot assay. The relationship between miR-127-5p and circ_0128846 or NAMPT was predicted by bioinformatics tools and verified by dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Results Circ_0128846 and NAMPT were upregulated and miR-127-5p was downregulated in OA cartilage tissues. Knockdown of circ_0128846 increased cell viability and inhibited apoptosis, inflammation and ECM degradation in OA chondrocytes, while these effects were reversed by downregulating miR-127-5p. Moreover, circ_0128846 positively regulated NAMPT expression by sponging miR-127-5p. Furthermore, miR-127-5p promoted cell viability and suppressed apoptosis, inflammation, and ECM degradation in OA chondrocytes by directly targeting NAMPT. Conclusion Circ_0128846 knockdown might inhibit the progression of OA by upregulating miR-127-5p and downregulating NAMPT, offering a new insight into the potential application of circ_0128846 in OA treatment.

scholarly journals Circ_0020093 ameliorates IL-1β-induced apoptosis and extracellular matrix degradation of human chondrocytes by upregulating SPRY1 via targeting miR-23b

2021 ◽  
Author(s):  
Mingli Feng ◽  
Lin Jing ◽  
Jingbo Cheng ◽  
Shuai An ◽  
Jiang Huang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Model ◽  
Interleukin 1 ◽  
Cartilage Degeneration ◽  
Human Chondrocytes ◽  
Luciferase Reporter ◽  
Chondrocyte Apoptosis ◽  
Qrt Pcr ◽  
Ecm Degradation ◽  
Induced Apoptosis

AbstractOsteoarthritis (OA) is a chronic disease characterized by articular cartilage degeneration and uncontrolled chondrocyte apoptosis. At present, accumulating evidence introduces that circular RNA (circRNA) is involved in the development of OA. The aim of our study was to explore the role and the functional mechanism of circ_0020093 in OA cell model. Human chondrocytes were treated with interleukin-1 beta (IL-1β) to construct OA model. The expression of circ_0020093, miR-23b, and Sprouty 1 (SPRY1) mRNA was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell apoptosis was assessed by flow cytometry assay. The expression of extracellular matrix (ECM)-associated markers and SPRY1 protein level was detected by qRT-PCR and Western blot. Bioinformatics analysis-predicted relationship between miR-23b and circ_0020093 or SPRY1 was further verified by dual-luciferase reporter assay and RNA pull-down assay. In this study, we found that the expression of circ_0020093 and SPRY1 was declined, while miR-23b expression was elevated in IL-1β-treated chondrocytes. IL-1β induced chondrocyte apoptosis and ECM degradation, while these negative effects were alleviated by circ_0020093 overexpression or miR-23b inhibition. MiR-23b was a target of circ_0020093, and SPRY1 was a downstream target of miR-23b. Rescue experiments showed that miR-23b enrichment reversed the role of circ_0020093 overexpression, and SPRY1 knockdown also reversed the effects of miR-23b inhibition. Importantly, circ_0020093 positively regulated SPRY1 expression by targeting miR-23b. In conclusion, circ_0020093 ameliorates IL-1β-induced apoptosis and ECM degradation of human chondrocytes by regulating the miR-23b/SPRY1 axis.

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