Skip to content
2000
image of Jiangu Recipe Suppresses ER Stress-Induced Apoptosis and Inhibits Extracellular Matrix Degradation in Chondrocytes through Upregulating SIRT1 Expression

Abstract

Objective

This study aimed to explore the effects of Jiangu Recipe (JGR) on chondrocyte responses under tert-Butyl hydroperoxide (TBHP)-induced oxidative stress, specifically focusing on apoptosis and extracellular matrix (ECM) degradation.

Methods

Chondrocytes were treated with varying JGR concentrations, and cell viability was assessed. The impact of JGR on TBHP-induced apoptosis and protein expression levels of apoptosis-related molecules (Bcl-2, Bax, and cleaved caspase-3) and ECM components (Collagen II, Aggrecan, MMP-13) was evaluated.

Results

JGR exhibited protective effects against oxidative stress in chondrocytes. Moreover, it maintained cell viability under tert-butyl hydroperoxide (TBHP) induction, suppressing apoptosis (Bax, cleaved caspase-3) and enhancing anti-apoptotic Bcl-2. JGR also attenuated extracellular matrix (ECM) degradation, promoting Collagen II and Aggrecan while reducing MMP-13 expression. Investigating endoplasmic reticulum (ER) stress, it was found that JGR downregulated TBHP-induced GRP78, CHOP, ATF4, p-PERK, and p-eIF2α, thus indicating ER stress modulation. SIRT1 played a key role, as JGR upregulated SIRT1, mitigating TBHP-induced downregulation. SIRT1 knockdown reversed JGR's protective effects, highlighting its crucial role in JGR-mediated responses.

Conclusion

Our findings suggest that JGR mitigated TBHP-induced chondrocyte apoptosis and ECM degradation, highlighting its potential therapeutic application in osteoarthritis. Mechanistically, our study highlights that SIRT1 plays a crucial role in mediating the protective effects of JGR against ER stress-induced chondrocyte apoptosis and ECM degradation, providing a foundation for further clinical exploration in managing osteoarthritic conditions.

Loading

Article metrics loading...

/content/journals/cpb/10.2174/0113892010316076240924072658
2024-10-09
2024-11-19
Loading full text...

Full text loading...

References

  1. Charlier E. Deroyer C. Ciregia F. Malaise O. Neuville S. Plener Z. Malaise M. de Seny D. Chondrocyte dedifferentiation and osteoarthritis (OA). Biochem. Pharmacol. 2019 165 49 65 10.1016/j.bcp.2019.02.036 30853397
    [Google Scholar]
  2. Zheng L. Zhang Z. Sheng P. Mobasheri A. The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis. Ageing Res. Rev. 2021 66 101249 10.1016/j.arr.2020.101249 33383189
    [Google Scholar]
  3. Quicke J.G. Conaghan P.G. Corp N. Peat G. Osteoarthritis year in review 2021: Epidemiology & therapy. Osteoarthritis Cartilage 2022 30 2 196 206 10.1016/j.joca.2021.10.003 34695571
    [Google Scholar]
  4. Emery C.A. Whittaker J.L. Mahmoudian A. Lohmander L.S. Roos E.M. Bennell K.L. Toomey C.M. Reimer R.A. Thompson D. Ronsky J.L. Kuntze G. Lloyd D.G. Andriacchi T. Englund M. Kraus V.B. Losina E. Bierma-Zeinstra S. Runhaar J. Peat G. Luyten F.P. Snyder-Mackler L. Risberg M.A. Mobasheri A. Guermazi A. Hunter D.J. Arden N.K. Establishing outcome measures in early knee osteoarthritis. Nat. Rev. Rheumatol. 2019 15 7 438 448 10.1038/s41584‑019‑0237‑3 31201386
    [Google Scholar]
  5. Berenbaum F. Meng Q.J. The brain–joint axis in osteoarthritis: Nerves, circadian clocks and beyond. Nat. Rev. Rheumatol. 2016 12 9 508 516 10.1038/nrrheum.2016.93 27305851
    [Google Scholar]
  6. Hunter D.J. March L. Chew M. Osteoarthritis in 2020 and beyond: A Lancet Commission. Lancet 2020 396 10264 1711 1712 10.1016/S0140‑6736(20)32230‑3 33159851
    [Google Scholar]
  7. Xie Y. Zinkle A. Chen L. Mohammadi M. Fibroblast growth factor signalling in osteoarthritis and cartilage repair. Nat. Rev. Rheumatol. 2020 16 10 547 564 10.1038/s41584‑020‑0469‑2 32807927
    [Google Scholar]
  8. Schulze-Tanzil G. Intraarticular ligament degeneration is interrelated with cartilage and bone destruction in osteoarthritis. Cells 2019 8 9 990 10.3390/cells8090990 31462003
    [Google Scholar]
  9. Sanchez-Lopez E. Coras R. Torres A. Lane N.E. Guma M. Synovial inflammation in osteoarthritis progression. Nat. Rev. Rheumatol. 2022 18 5 258 275 10.1038/s41584‑022‑00749‑9 35165404
    [Google Scholar]
  10. Hodgkinson T. Kelly D.C. Curtin C.M. O’Brien F.J. Mechanosignalling in cartilage: An emerging target for the treatment of osteoarthritis. Nat. Rev. Rheumatol. 2022 18 2 67 84 10.1038/s41584‑021‑00724‑w 34934171
    [Google Scholar]
  11. Shi Y. Hu X. Cheng J. Zhang X. Zhao F. Shi W. Ren B. Yu H. Yang P. Li Z. Liu Q. Liu Z. Duan X. Fu X. Zhang J. Wang J. Ao Y. A small molecule promotes cartilage extracellular matrix generation and inhibits osteoarthritis development. Nat. Commun. 2019 10 1 1914 10.1038/s41467‑019‑09839‑x 31015473
    [Google Scholar]
  12. Hwang H. Kim H. Chondrocyte apoptosis in the pathogenesis of osteoarthritis. Int. J. Mol. Sci. 2015 16 11 26035 26054 10.3390/ijms161125943 26528972
    [Google Scholar]
  13. Tudorachi N.B. Totu E.E. Fifere A. Ardeleanu V. Mocanu V. Mircea C. Isildak I. Smilkov K. Cărăuşu E.M. The implication of reactive oxygen species and antioxidants in knee osteoarthritis. Antioxidants 2021 10 6 985 10.3390/antiox10060985 34205576
    [Google Scholar]
  14. Ansari M.Y. Ahmad N. Haqqi T.M. Oxidative stress and inflammation in osteoarthritis pathogenesis: Role of polyphenols. Biomed. Pharmacother. 2020 129 110452 10.1016/j.biopha.2020.110452 32768946
    [Google Scholar]
  15. Feng K. Chen Z. Pengcheng L. Zhang S. Wang X. Quercetin attenuates oxidative stress‐induced apoptosis via SIRT1/AMPK‐mediated inhibition of ER stress in rat chondrocytes and prevents the progression of osteoarthritis in a rat model. J. Cell. Physiol. 2019 234 10 18192 18205 10.1002/jcp.28452 30854676
    [Google Scholar]
  16. Feng K. Ge Y. Chen Z. Li X. Liu Z. Li X. Li H. Tang T. Yang F. Wang X. Curcumin inhibits the PERK-eIF2α-CHOP pathway through promoting SIRT1 expression in oxidative stress-induced rat chondrocytes and ameliorates osteoarthritis progression in a rat model. Oxid. Med. Cell. Longev. 2019 2019 1 17 10.1155/2019/8574386
    [Google Scholar]
  17. Xiaodong L. Xinping S. Xuyi T. Haien L. Canyu H. Gang H. Daowei Z. Kejian Z. Zhitong Jiangu decoction mitigates osteoarthritis in rabbits via regulation of NF-κB signaling pathway. Trop. J. Pharm. Res. 2022 20 4 741 748 10.4314/tjpr.v20i4.12
    [Google Scholar]
  18. Liu H. Li Z. Zhang X. Pu X.W. Lin R.L. Jing C.Y. Liu C.F. Effect of Jiangu Shenjin decoction on the Wnt/β-catenin signalling pathway in knee osteoarthritis. Traditional Medicine Research 2022 7 6 54 10.53388/TMR20220401001
    [Google Scholar]
  19. Chen Z-J. Huo X-Q. Ren Y. Shu Z. Zhang Y-L. Anti-osteoarthritis components and mechanism of Fufang Duzhong Jiangu Granules. Zhongguo Zhongyao Zazhi 2022 47 15 4156 4163 36046906
    [Google Scholar]
  20. Yan Y. He M. Zhao L. Wu H. Zhao Y. Han L. Wei B. Ye D. Lv X. Wang Y. Yao W. Zhao H. Chen B. Jin Z. Wen J. Zhu Y. Yu T. Jin F. Wei M. A novel HIF-2α targeted inhibitor suppresses hypoxia-induced breast cancer stemness via SOD2-mtROS-PDI/GPR78-UPRER axis. Cell Death Differ. 2022 29 9 1769 1789 10.1038/s41418‑022‑00963‑8 35301432
    [Google Scholar]
  21. Xiang C. Wang Y. Zhang H. Han F. The role of endoplasmic reticulum stress in neurodegenerative disease. Apoptosis 2017 22 1 1 26 10.1007/s10495‑016‑1296‑4 27815720
    [Google Scholar]
  22. Shen M. Wang L. Wang B. Wang T. Yang G. Shen L. Wang T. Guo X. Liu Y. Xia Y. Jia L. Wang X. Activation of volume-sensitive outwardly rectifying chloride channel by ROS contributes to ER stress and cardiac contractile dysfunction: Involvement of CHOP through Wnt. Cell Death Dis. 2014 5 11 e1528 e1528 10.1038/cddis.2014.479 25412307
    [Google Scholar]
  23. Hosoi T. Saito A. Kume A. Okuma Y. Nomura Y. Ozawa K. Vanadate inhibits endoplasmic reticulum stress responses. Eur. J. Pharmacol. 2008 594 1-3 44 48 10.1016/j.ejphar.2008.07.034 18700142
    [Google Scholar]
  24. Feng Y. Sokol E.S. Del Vecchio C.A. Sanduja S. Claessen J.H.L. Proia T.A. Jin D.X. Reinhardt F. Ploegh H.L. Wang Q. Gupta P.B. Epithelial-to-mesenchymal transition activates PERK-eIF2α and sensitizes cells to endoplasmic reticulum stress. Cancer Discov. 2014 4 6 702 715 10.1158/2159‑8290.CD‑13‑0945 24705811
    [Google Scholar]
  25. Rozpedek W. Pytel D. Mucha B. Leszczynska H. Diehl J.A. Majsterek I. The role of the PERK/eIF2α/ATF4/CHOP signaling pathway in tumor progression during endoplasmic reticulum stress. Curr. Mol. Med. 2016 16 6 533 544 10.2174/1566524016666160523143937 27211800
    [Google Scholar]
  26. Rozpedek W. Markiewicz L. Diehl J. Pytel D. Majsterek I. Unfolded protein response and PERK kinase as a new therapeutic target in the pathogenesis of Alzheimer’s disease. Curr. Med. Chem. 2015 22 27 3169 3184 10.2174/0929867322666150818104254 26282939
    [Google Scholar]
  27. Wang Y. Luo J. Yang H. Liu Y. LncRNA Peg13 alleviates myocardial infarction/reperfusion injury through regulating MiR-34a/Sirt1-mediated endoplasmic reticulum stress Int. Heart J. 2024 65 3 517 527 10.1536/ihj.23‑453 38825496
    [Google Scholar]
  28. Li F. Chang Z. Li Y. Sun J. In vivo and in vitro impact of atorvastatin against myocardial ischaemia-reperfusion injury by upregulation of silent information regulator l and attenuation of endoplasmic reticulum stress-induced apoptosis. J. Drug Target. 2022 30 10 1 12 10.1080/1061186X.2022.2091577 35722944
    [Google Scholar]
  29. Zhang Y. He L. Tu M. Huang M. Chen Y. Pan D. Peng J. Shen X. The ameliorative effect of terpinen-4-ol on ER stress-induced vascular calcification depends on SIRT1-mediated regulation of PERK acetylation. Pharmacol. Res. 2021 170 105629 10.1016/j.phrs.2021.105629 34089864
    [Google Scholar]
  30. Spitz A.Z. Gavathiotis E. Physiological and pharmacological modulation of BAX. Trends Pharmacol. Sci. 2022 43 3 206 220 10.1016/j.tips.2021.11.001 34848097
    [Google Scholar]
  31. Jiang M. Qi L. Li L. Li Y. The caspase-3/GSDME signal pathway as a switch between apoptosis and pyroptosis in cancer. Cell Death Discov. 2020 6 1 112 10.1038/s41420‑020‑00349‑0 33133646
    [Google Scholar]
  32. Flores-Romero H. Hohorst L. John M. Albert M.C. King L.E. Beckmann L. Szabo T. Hertlein V. Luo X. Villunger A. Frenzel L.P. Kashkar H. Garcia-Saez A.J. BCL‐2‐family protein tBID can act as a BAX‐like effector of apoptosis. EMBO J. 2022 41 2 e108690 10.15252/embj.2021108690 34931711
    [Google Scholar]
  33. Zhang X. Han L. Zong H. Ding K. Yuan Y. Bai J. Zhou Y. Zhang B. Zhu J. Enhanced production of anti-PD1 antibody in CHO cells through transient co-transfection with anti-apoptotic genes Bcl-x L and Mcl-1. Bioprocess Biosyst. Eng. 2018 41 5 633 640 10.1007/s00449‑018‑1898‑z 29368032
    [Google Scholar]
  34. Ning R. Chen G. Fang R. Zhang Y. Zhao W. Qian F. Diosmetin inhibits cell proliferation and promotes apoptosis through STAT3/c-Myc signaling pathway in human osteosarcoma cells. Biol. Res. 2021 54 1 40 10.1186/s40659‑021‑00363‑1 34922636
    [Google Scholar]
  35. Ren M.T. Gu M.L. Zhou X.X. Yu M.S. Pan H.H. Ji F. Ding C.Y. Sirtuin 1 alleviates endoplasmic reticulum stress-mediated apoptosis of intestinal epithelial cells in ulcerative colitis. World J. Gastroenterol. 2019 25 38 5800 5813 10.3748/wjg.v25.i38.5800 31636473
    [Google Scholar]
  36. Wang F. Yao S. Xia H. SIRT1 is a key regulatory target for the treatment of the endoplasmic reticulum stress-related organ damage. Biomed. Pharmacother. 2020 130 110601 10.1016/j.biopha.2020.110601 32784049
    [Google Scholar]
  37. Philippe C. Jaud M. Féral K. Gay A. Van Den Berghe L. Farce M. Bousquet M. Pyronnet S. Mazzolini L. Rouault-Pierre K. Touriol C. Pivotal role of the endoplasmic reticulum stress-related XBP1s/miR-22/SIRT1 axis in acute myeloid leukemia apoptosis and response to chemotherapy. Leukemia 2024 38 8 1764 1776 10.1038/s41375‑024‑02321‑8 38909090
    [Google Scholar]
/content/journals/cpb/10.2174/0113892010316076240924072658
Loading
/content/journals/cpb/10.2174/0113892010316076240924072658
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keywords: endoplasmic reticulum stress ; Jiangu recipe ; oxidative stress ; SIRT1 ; apoptosis
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test