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Scutellarein Ameliorated Chondrocyte Inflammation and Osteoarthritis in Rats

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Abstract

Objective

Osteoarthritis (OA) is a degenerative joint disorder characterized by the gradual degradation of joint cartilage and local inflammation. This study aimed to investigate the anti-OA effect of scutellarein (SCU), a single-unit flavonoid compound obtained from Scutellaria barbata D. Don, in rats.

Methods

The extracted rat chondrocytes were treated with SCU and IL-1β. The chondrocytes were divided into control group, IL-1β group, IL-1β+SCU 50 µmol/L group, and IL-1β+SCU 100 µmol/L group. Morphology of rat chondrocytes was observed by toluidine blue and safranin O staining. CCK-8 method was used to detect the cytotoxicity of SCU. ELISA, qRT-PCR, Western blotting, immunofluorescence, SAβ-gal staining, flow cytometry, and bioinformatics analysis were applied to evaluate the effect of SCU on rat chondrocytes under IL-1β intervention. Additionally, anterior cruciate ligament transection (ACL-T) was used to establish a rat OA model. Histological changes were detected by safranin O/fast green, hematoxylin-eosin (HE) staining, and immunohistochemistry.

Results

SCU protected cartilage and exhibited anti-inflammatory effects via multiple mechanisms. Specifically, it could enhance the synthesis of extracellular matrix in cartilage cells and inhibit its degradation. In addition, SCU partially inhibited the nuclear factor kappa-B/mitogen-activated protein kinase (NF-κB/MAPK) pathway, thereby reducing inflammatory cytokine production in the joint cartilage. Furthermore, SCU significantly reduced IL-1β-induced apoptosis and senescence in rat chondrocytes, further highlighting its potential role in OA treatment. In vivo experiments revealed that SCU (at a dose of 50 mg/kg) administered for 2 months could significantly delay the progression of cartilage damage, which was reflected in a lower Osteoarthritis Research Society International (OARSI) score, and reduced expression of matrix metalloproteinase 13 (MMP13) in cartilage.

Conclusion

SCU is effective in the therapeutic management of OA and could serve as a potential candidate for future clinical drug therapy for OA.

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References

  1. Glyn-Jones S, Palmer AJ, Agricola R, et al. Osteoarthritis. Lancet, 2015,386(9991):376–387

    Article  CAS  PubMed  Google Scholar 

  2. Barnett R. Osteoarthritis. Lancet, 2018,391(10134):1985

    Article  PubMed  Google Scholar 

  3. Hunter DJ, Bierma-Zeinstra S. Osteoarthritis. Lancet, 2019,393(10182):1745–1759

    Article  CAS  PubMed  Google Scholar 

  4. Kapoor M, Martel-Pelletier J, Lajeunesse D, et al. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol, 2011,7(1):33–42

    Article  CAS  PubMed  Google Scholar 

  5. Armendáriz-Barragán B, Zafar N, Badri W, et al. Plant extracts: from encapsulation to application. Expert Opin Drug Deliv, 2016,13(8):1165–75

    Article  PubMed  Google Scholar 

  6. Liu D, Zhang C, Hu M, et al. Scutellarein relieves the death and inflammation of tubular epithelial cells in ischemic kidney injury by degradation of COX-2 protein. Int Immunopharmacol, 2021,101(Pt A):108193

    Article  CAS  PubMed  Google Scholar 

  7. Park MY, Ha SE, Kim HH, et al. Scutellarein Inhibits LPS-Induced Inflammation through NF-κB/MAPKs Signaling Pathway in RAW264.7 Cells. Molecules, 2022,27(12):3782

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lang X, Chen Z, Yang X, et al. Scutellarein induces apoptosis and inhibits proliferation, migration, and invasion in ovarian cancer via inhibition of EZH2/FOXO1 signaling. J Biochem Mol Toxicol, 2021,35(10):e22870

    Article  CAS  PubMed  Google Scholar 

  9. Guo F, Yang F, Zhu YH. Scutellarein from Scutellaria barbata induces apoptosis of human colon cancer HCT116 cells through the ROS-mediated mitochondria-dependent pathway. Nat Prod Res, 2019,33(16):2372–2375

    Article  CAS  PubMed  Google Scholar 

  10. Ha SE, Kim SM, Lee HJ, et al. Scutellarein Induces Fas-Mediated Extrinsic Apoptosis and G2/M Cell Cycle Arrest in Hep3B Hepatocellular Carcinoma Cells. Nutrients, 2019,11(2):263

    Article  CAS  PubMed Central  Google Scholar 

  11. Ding Q, Zhang R, Sheng G, et al. Dioscin alleviates the progression of osteoarthritis: an in vitro and in vivo study. J Inflamm (Lond), 2023,20(1):14

    Article  CAS  PubMed  Google Scholar 

  12. Liu X, Ouyang S, Yu B, et al. PharmMapper server: a web server for potential drug target identification using pharmacophore mapping approach. Nucleic Acids Res, 2010,38(Web Server issue):W609–W614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bardou P, Mariette J, Escudié F, et al. Jvenn: an interactive Venn diagram viewer. BMC Bioinformatics, 2014,15(1):293

    Article  PubMed  PubMed Central  Google Scholar 

  14. Gu Z, Gu L, Eils R, et al. circlize implements and enhances circular visualization in R. Bioinformatics, 2014,30(19):2811–2812

    Article  CAS  PubMed  Google Scholar 

  15. Zhou Y, Zhou B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systemslevel datasets. Nat Commun, 2019,10(1):1523

    Article  PubMed  PubMed Central  Google Scholar 

  16. Chu X, You H, Yuan X, et al. Protective effect of lentivirus-mediated siRNA targeting ADAMTS-5 on cartilage degradation in a rat model of osteoarthritis. Int J Mol Med, 2013,31(5):1222–1228

    Article  CAS  PubMed  Google Scholar 

  17. Sun K, Luo J, Jing X, et al. Hyperoside ameliorates the progression of osteoarthritis: An in vitro and in vivo study. Phytomedicine, 2021,80:153387

    Article  CAS  PubMed  Google Scholar 

  18. Lu R, Wang YG, Qu Y, et al. Dihydrocaffeic acid improves IL-1β-induced inflammation and cartilage degradation via inhibiting NF-κB and MAPK signalling pathways. Bone Joint Res, 2023,12(4):259–273

    Article  PubMed  PubMed Central  Google Scholar 

  19. Aydelotte MB, Kuettner KE. Differences between subpopulations of cultured bovine articular chondrocytes. I. Morphology and cartilage matrix production. Connect Tissue Res, 1988,18(3):205–222

    CAS  PubMed  Google Scholar 

  20. Rim YA, Nam Y, Ju JH. The Role of Chondrocyte Hypertrophy and Senescence in Osteoarthritis Initiation and Progression. Int J Mol Sci, 2020,21(7):2358

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tu C, Huang X, Xiao Y, et al. Schisandrin A Inhibits the IL-1β-Induced Inflammation and Cartilage Degradation via Suppression of MAPK and NF-κB Signal Pathways in Rat Chondrocytes. Front Pharmacol, 2019,10:41

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Richards MM, Maxwell JS, Weng L, et al. Intraarticular treatment of knee osteoarthritis: from anti-inflammatories to products of regenerative medicine. Phys Sportsmed, 2016,44(2):101–108

    Article  PubMed  PubMed Central  Google Scholar 

  23. Katz JA. COX-2 inhibition: what we learned—a controversial update on safety data. Pain Med, 2013,14(Suppl1):S29–S34

    Article  PubMed  Google Scholar 

  24. Lin S, Lu J, Chen Q, et al. Plantamajoside suppresses the activation of NF-κB and MAPK and ameliorates the development of osteoarthritis. Int Immunopharmacol, 2023,115:109582

    Article  CAS  PubMed  Google Scholar 

  25. Wang X, Guo Z, Lin J, et al. Indirubin protects chondrocytes and alleviates OA by inhibiting the MAPK and NF-κB pathways. Int Immunopharmacol, 2023,115:109624

    Article  CAS  PubMed  Google Scholar 

  26. Huang XW, Xu Y, Sui X, et al. Scutellarein suppresses Aβ-induced memory impairment via inhibition of the NF-κB pathway in vivo and in vitro. Oncol Lett, 2019,17(6):5581–5589

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Fu F, Shao S, Wang Z, et al. Scutellarein inhibits RANKL-induced osteoclast formation in vitro and prevents LPS-induced bone loss in vivo. J Cell Physiol, 2019,234(7):11951–11959

    Article  CAS  PubMed  Google Scholar 

  28. Sun S, Yan Z, Shui X, et al. Astilbin prevents osteoarthritis development through the TLR4/MD-2 pathway. J Cell Mol Med, 2020, 24(22):13104–13114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Mobasheri A, Rayman MP, Gualillo O, et al. The role of metabolism in the pathogenesis of osteoarthritis. Nat Rev Rheumatol, 2017,13(5):302–311

    Article  CAS  PubMed  Google Scholar 

  30. Motta F, Barone E, Sica A, et al. Inflammaging and Osteoarthritis. Clin Rev Allergy Immunol, 2023,64(2):222–238

    Article  CAS  PubMed  Google Scholar 

  31. Wan J, He Z, Peng R, et al. Injectable photocrosslinking spherical hydrogel-encapsulated targeting peptide-modified engineered exosomes for osteoarthritis therapy. J Nanobiotechnology, 2023,21(1):284

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Guo Q, Chen X, Chen J, et al. STING promotes senescence, apoptosis, and extracellular matrix degradation in osteoarthritis via the NF-κB signaling pathway. Cell Death Dis, 2021,12(1):13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Liu Y, Zhang Z, Li T, et al. Senescence in osteoarthritis: from mechanism to potential treatment. Arthritis Res Ther, 2022,24(1):174

    Article  PubMed  PubMed Central  Google Scholar 

  34. Qu Y, Wang Y, Wang S, et al. A comprehensive analysis of single-cell RNA transcriptome reveals unique SPP1+ chondrocytes in human osteoarthritis. Comput Biol Med, 2023,160:106926

    Article  CAS  PubMed  Google Scholar 

  35. Mobasheri A, Matta C, Zákány R, et al. Chondrosenescence: definition, hallmarks and potential role in the pathogenesis of osteoarthritis. Maturitas, 2015,80(3):237–244

    Article  CAS  PubMed  Google Scholar 

  36. Dulić V, Beney GE, Frebourg G, et al. Uncoupling between phenotypic senescence and cell cycle arrest in aging p21-deficient fibroblasts. Mol Cell Biol, 2000,20(18):6741–6754

    Article  PubMed  PubMed Central  Google Scholar 

  37. Chai B, Zheng ZH, Liao X, et al. The protective role of omentin-1 in IL-1β-induced chondrocyte senescence. Artif Cells Nanomed Biotechnol, 2020,48(1):8–14

    Article  CAS  PubMed  Google Scholar 

  38. Huang H, Lei H, Yang F, et al. Activation of the bile acid receptor GPBAR1 (TGR5) ameliorates interleukin-1β (IL-1β)-induced chondrocytes senescence. Biomed Pharmacother, 2018,106:1713–1719

    Article  CAS  PubMed  Google Scholar 

  39. Hwang HS, Kim HA. Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis. Int J Mol Sci, 2015,16(11):26035–26054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Berenbaum F. Osteoarthritis as an inflammatory disease (osteoarthritis is not osteoarthrosis!). Osteoarthritis Cartilage, 2013,21(1):16–21

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopedics, Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, 030032, China

    Shao-ze Jing, Shu-han Yang, Hai-hu Hao & Hua Wu

  2. Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

    Yun-kun Qu & Hua Wu

Authors
  1. Shao-ze Jing
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  2. Shu-han Yang
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  3. Yun-kun Qu
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  4. Hai-hu Hao
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  5. Hua Wu
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Corresponding authors

Correspondence to Hai-hu Hao or Hua Wu.

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The authors declare no competing interests.

Additional information

This study was financially sponsored by the National Natural Science Foundation of China (No. 51537004).

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Jing, Sz., Yang, Sh., Qu, Yk. et al. Scutellarein Ameliorated Chondrocyte Inflammation and Osteoarthritis in Rats. CURR MED SCI 44, 355–368 (2024). https://doi.org/10.1007/s11596-024-2854-6

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  • DOI: https://doi.org/10.1007/s11596-024-2854-6

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