Protective effect of resveratrol on obesity-related osteoarthritis via alleviating JAK2/STAT3 signaling pathway is independent of SOCS3

Jiang, Mengqi; He, Jianyi; Gu, Hailun; Yang, Yingchun; Huang, Yue; Xu, Xiaoling; Liu, Li

doi:10.1016/j.taap.2019.114871

Cited by 20 publications

(20 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 38 , 39 Our histological and behavioral observations confirmed that rats fed a HFD presented OA-like lesions, consistent with our previous and others’ studies. 40 , 41 Previously, oral administration of curcumin was shown to be effective in slowing the progression of OA in a post-traumatic OA mouse model. 42 However, doubts have been raised regarding whether oral curcumin can reach pharmacologically active concentrations in synovial fluid or joint tissues 43 and the oral bioavailability of curcumin is only 1%.…”

Section: Discussionmentioning

confidence: 99%

Curcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a

Yao¹,

Liu²,

Sun³

et al. 2021

JIR

Self Cite

View full text Add to dashboard Cite

Purpose The mechanism underlying curcumin’s protective effect on osteoarthritis (OA) has not been clarified. This study aimed to determine whether curcumin exerts a chondroprotective effect by inhibiting apoptosis via upregulation of E2F1/PITX1 and activation of autophagy via the Akt/mTOR pathway by targeting microRNA-34a (miR-34a). Methods Male Sprague–Dawley rats were fed a normal diet (ND) or high-fat diet (HFD) for 28 weeks. Five rats from each diet group were selected randomly for histological analysis of OA characteristics. Rats fed a HFD were given a single intra-stifle joint injection of the miR-34a mimic agomir-34a or negative control agomir (NC), followed by weekly low-dose (200 μg/kg body weight) or high-dose (400 μg/kg body weight) curcumin intra-joint injections from weeks 29 to 32. The rats’ stifle joints were submitted to histological analysis and to an apoptotic assay. Expression of miR-34a was detected using a real-time RT-PCR. E2F1 and PITX1 protein levels were determined by Western blot analysis, and the expressions of Beclin1, LC3B, p62, phosphorylated (p)-Akt, and p-mTOR were measured using immunofluorescence analysis. Results We found that rats fed a HFD had OA-like lesions in their articular cartilage and had increased apoptosis of chondrocytes and decreased autophagy compared to rats fed a ND. Curcumin treatment alleviated OA changes, inhibited apoptosis, and upregulated autophagy. Agomir-34a treatment reduced E2F1, PITX1, Beclin1, and LC3B expression and increased p62, p-Akt, and p-mTOR expression in HFD-fed rats given low- or high-dose curcumin. Greater numbers of apoptotic cells, lesser expression of p62, p-Akt, and p-mTOR, and greater expression of E2F1, PITX1, and LC3B were observed in the agomir-34a and high-dose curcumin-treated group than in agomir-34a and low-dose curcumin-treated group. Conclusion Curcumin’s chondroprotective effect was mediated by its suppression of miR-34a, apparently by reducing apoptosis, via upregulation of E2F1/PITX1, and by augmenting autophagy, likely via the Akt/mTOR pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Curcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a

Yao¹,

Liu²,

Sun³

et al. 2021

JIR

Self Cite

View full text Add to dashboard Cite

show abstract

“…In C57BL/6 mice prone to developing OA and subjected to a high-fat diet, oral treatment with resveratrol showed benefits in slowing down the progression of the pathology in comparison to a control group [129,130]. In the same model, a delay of cartilage degradation was also linked to a resveratrol-induced activation of autophagy [131], and a protective role was attributed to the modulation of the JAK2/STAT3 (Janus kinase 2/signal transducer and activator of transcription 3) pathway [132]. In a recent study, Jin and colleagues addressed the increasingly significant topic of miRNA by linking resveratrol treatment with a chondroprotective effect exerted by the regulation of miR-146 in a LPS-induced OA model in vitro [133].…”

Section: Resveratrolmentioning

confidence: 99%

Nutraceutical Activity in Osteoarthritis Biology: A Focus on the Nutrigenomic Role

D’Adamo

Cetrullo

Panichi

et al. 2020

Cells

View full text Add to dashboard Cite

Osteoarthritis (OA) is a disease associated to age or conditions that precipitate aging of articular cartilage, a post-mitotic tissue that remains functional until the failure of major homeostatic mechanisms. OA severely impacts the national health system costs and patients’ quality of life because of pain and disability. It is a whole-joint disease sustained by inflammatory and oxidative signaling pathways and marked epigenetic changes responsible for catabolism of the cartilage extracellular matrix. OA usually progresses until its severity requires joint arthroplasty. To delay this progression and to improve symptoms, a wide range of naturally derived compounds have been proposed and are summarized in this review. Preclinical in vitro and in vivo studies have provided proof of principle that many of these nutraceuticals are able to exert pleiotropic and synergistic effects and effectively counteract OA pathogenesis by exerting both anti-inflammatory and antioxidant activities and by tuning major OA-related signaling pathways. The latter are the basis for the nutrigenomic role played by some of these compounds, given the marked changes in the transcriptome, miRNome, and methylome. Ongoing and future clinical trials will hopefully confirm the disease-modifying ability of these bioactive molecules in OA patients.

show abstract

“…Primary chondrocytes were isolated from newborn SD rats as described previously [ 15 ]. Briefly, the articular cartilages of rats were dissected and dissociated, and the cells were cultured using DMEM/F12 medium with 10% fetal bovine serum at 37°C and 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Leptin Induced TLR4 Expression via the JAK2-STAT3 Pathway in Obesity-Related Osteoarthritis

Jiang

Sun

et al. 2021

Oxidative Medicine and Cellular Longevity

Self Cite

View full text Add to dashboard Cite

Obesity is considered as a risk factor of osteoarthritis (OA), but the precise relationship is still poorly understood. Leptin, one of the most relevant factors secreted by adipose tissues, plays an important role in the pathogenesis of OA. Our aim was to investigate the regulation and molecular mechanism of the leptin signaling pathway in obesity-related OA. SD rats were fed with a high-fat diet (HFD) for 5, 15, and 27 weeks. The levels of leptin in serum increased from W5, while in the synovial fluid increased from W15. The histological evaluation showed that the pathological changes of OA occurred at 27 weeks rather than 5 or 15 weeks. We also found that leptin induced CD14/TLR4 activation by the JAK2-STAT3 signaling pathway to promote OA. Moreover, silencing SOCS3 enhanced leptin-induced JAK2-STAT3-CD14/TLR4 activation in rat primary chondrocytes. Our findings indicated that leptin may be one of the initiating factors of obesity-related OA. TLR4 is at least partially regulated by leptin through the JAK2-STAT3-CD14 pathway. Meanwhile, SOCS3 acting as a negative feedback inhibitor of leptin signaling presented a potential therapeutic prospect for obesity-related OA. Our study provided new evidence suggesting the key role of leptin in mediating obesity-related OA process and its underlying mechanisms.

show abstract

Protective effect of resveratrol on obesity-related osteoarthritis via alleviating JAK2/STAT3 signaling pathway is independent of SOCS3

Cited by 20 publications

References 35 publications

Curcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a

Curcumin-Alleviated Osteoarthritic Progression in Rats Fed a High-Fat Diet by Inhibiting Apoptosis and Activating Autophagy via Modulation of MicroRNA-34a

Nutraceutical Activity in Osteoarthritis Biology: A Focus on the Nutrigenomic Role

Leptin Induced TLR4 Expression via the JAK2-STAT3 Pathway in Obesity-Related Osteoarthritis

Contact Info

Product

Resources

About