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The Abiwaijiwuli-Mufasili Attenuates Cartilage Damage and Ameliorates Osteoarthritis In vivo and In vitro By Regulating Serpina3-Mediated Wnt/b-Catenin Pathway

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Open Access
Article Type Original Article
Subject Medicine Group
OCLC JBRES Record
Qin Ma, Xinyi Liu, Xiaomin Wang, Rui Liu, Jingjing Li, Jialin Wu, Zhe Xu, Peipei Wang and Wei Chen*
Issue: Volume6-Issue6
Pages: 792-807
Received: 2025-06-20
Accepted: 2025-06-26
Published: 2025-06-30

Abstract

Introduction: Aibiwajiwuli-Mufasili (ABYJ), an ancient classic formula of Uyghur medicine, is used to treat osteoarthritis (OA) in clinical practice in China, yet the underlying mechanism remains obscure. We aimed to propose a novel therapeutic effect of ABYJ on the MIA-induced OA model and ATDC5 cell inflammatory model, and further demonstrated the cartilage renovation of OA through the Serpina3-mediated Wnt/β-catenin pathway.

Methods: In this study, the chemical composition of ABYJ were elucidated using optimized ultrahigh-performance liquid chromatography coupled with quadrupole exactive-orbitrap mass spectrometry (UPLC-Q-Exactive-orbitrap-MS). In an in vivo experiment, rats were randomly divided into 6 groups, the OA model in rats were induced by intraarticular injection with sodium iodoacetate (MIA) solution (60mg·mL-1), behavior of model animals were evaluated by Lequesne MG, and Micro-CT imaging was used for morphological evaluation, Hematoxylin-Eosin (HE) and Safranin O-fast green (SF) staining were used for histology assessment. In addition, 4D Label-free quantification proteomics analysis was used to further explore proteins differentially expressed after different treatment. The expression of Serpina3 and proteins on the Wnt/β-catenin signaling pathway in the rats OA models were determined by Western blot. In vitro, a LPS-induced ATDC5 cells inflammation model was used to validate the possible active ingredients and signaling pathway.

Result: Our studies had shown that a total of 75 active ingredients of ABYJ formula were identified by UPLC-Q-Exactive-orbitrap-MS, Ten marker compounds were identified using orthogonal partial least-squares discrimination analysis, which indicated colchicine and aloin may be the material basis for ABYJ. ABYJ reversed MIA-induced behavioral characteristics, articular inflammatory lesions, the pathological changes and micro structure of knee joint tissue, balance conversion of cartilage cell in rat and reduced the protein expression level of wnt5a, β-catenin and MMP13, while increased Serpina3. A similar rule was demonstrated, the result in vitro suggested ABYJ could inhibit LPS-induced overproduction of pro-inflammatory mediators in ATDC5 cells, including IL-1β, TNF-α and increased the expression level of Serpina3, the increasing expression of Serpina3 would induce [Ca2+] i influx, accordingly, chondrocyte apoptosis was inhibited.

Conclusion: These findings suggest that ABYJ exerts therapeutic effects on joint inflammation and cartilage damage by regulating the wnt5a/β-catenin signaling pathway and modulating the expression of key proteins such as Serpina3, highlighting its potential as a promising candidate for the treatment of joint-related diseases.

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© 2025 Xinyi L, et al., Distributed under Creative Commons CC-BY 4.0 Creative CommonsAttribution

How to cite this article

Ma Q, Liu X, Wang X, Liu R, Li J, Wu J, Xu Z, Wang P, Chen W. The Abiwaijiwuli-Mufasili Attenuates Cartilage Damage and Ameliorates Osteoarthritis In vivo and In vitro By Regulating Serpina3-Mediated Wnt/Î’-Catenin Pathway. J Biomed Res Environ Sci. 2025 Jun 30; 6(6): 792-807. doi: 10.37871/jbres2132, Article ID: JBRES2132, Available at: https://www. jelsciences.com/articles/jbres2132.pdf

Subject area(s)

OrthopedicsTherapeutics

References

  1. Yao Q, Wu X, Tao C, Gong W, Chen M, Qu M, Zhong Y, He T, Chen S, Xiao G. Osteoarthritis: pathogenic signaling pathways and therapeutic targets. Signal Transduct Target Ther. 2023 Feb 3;8(1):56. doi: 10.1038/s41392-023-01330-w. PMID: 36737426; PMCID: PMC9898571.
  2. Hunter DJ, March L, Chew M. Osteoarthritis in 2020 and beyond: a Lancet Commission. Lancet. 2020 Nov 28;396(10264):1711-1712. doi: 10.1016/S0140-6736(20)32230-3. Epub 2020 Nov 4. PMID: 33159851.
  3. Xie J, Wang Y, Lu L, Liu L, Yu X, Pei F. Cellular senescence in knee osteoarthritis: molecular mechanisms and therapeutic implications. Ageing Res Rev. 2021 Sep;70:101413. doi: 10.1016/j.arr.2021.101413. Epub 2021 Jul 21. PMID: 34298194.
  4. Robinson WH, Lepus CM, Wang Q, Raghu H, Mao R, Lindstrom TM, Sokolove J. Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2016 Oct;12(10):580-92. doi: 10.1038/nrrheum.2016.136. Epub 2016 Aug 19. PMID: 27539668; PMCID: PMC5500215.
  5. Visser AW, de Mutsert R, le Cessie S, den Heijer M, Rosendaal FR, Kloppenburg M; NEO Study Group. The relative contribution of mechanical stress and systemic processes in different types of osteoarthritis: the NEO study. Ann Rheum Dis. 2015 Oct;74(10):1842-7. doi: 10.1136/annrheumdis-2013-205012. Epub 2014 May 20. PMID: 24845389..
  6. Geng R, Li J, Yu C, Zhang C, Chen F, Chen J, Ni H, Wang J, Kang K, Wei Z, Xu Y, Jin T. Knee osteoarthritis: Current status and research progress in treatment (Review). Exp Ther Med. 2023 Aug 25;26(4):481. doi: 10.3892/etm.2023.12180. PMID: 37745043; PMCID: PMC10515111.
  7. Joiner DM, Less KD, Van Wieren EM, Zhang YW, Hess D, Williams BO. Accelerated and increased joint damage in young mice with global inactivation of mitogen-inducible gene 6 after ligament and meniscus injury. Arthritis Res Ther. 2014 Mar 27;16(2):R81. doi: 10.1186/ar4522. PMID: 24670222; PMCID: PMC4060238.
  8. Gunaratne R, Pratt DN, Banda J, Fick DP, Khan RJK, Robertson BW. Patient Dissatisfaction Following Total Knee Arthroplasty: A Systematic Review of the Literature. J Arthroplasty. 2017 Dec;32(12):3854-3860. doi: 10.1016/j.arth.2017.07.021. Epub 2017 Jul 21. PMID: 28844632.
  9. Katz JN, Arant KR, Loeser RF. Diagnosis and Treatment of Hip and Knee Osteoarthritis: A Review. JAMA. 2021 Feb 9;325(6):568-578. doi: 10.1001/jama.2020.22171. PMID: 33560326; PMCID: PMC8225295.
  10. Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell. 2012 Jun 8;149(6):1192-205. doi: 10.1016/j.cell.2012.05.012. PMID: 22682243.
  11. Gan L, Deng Z, Wei Y, Li H, Zhao L. Decreased expression of GEM in osteoarthritis cartilage regulates chondrogenic differentiation via Wnt/β-catenin signaling. J Orthop Surg Res. 2023 Oct 4;18(1):751. doi: 10.1186/s13018-023-04236-z. PMID: 37794464; PMCID: PMC10548561.
  12. Yang Y, Topol L, Lee H, Wu J. Wnt5a and Wnt5b exhibit distinct activities in coordinating chondrocyte proliferation and differentiation. Development. 2003 Mar;130(5):1003-15. doi: 10.1242/dev.00324. PMID: 12538525.
  13. Bradley EW, Drissi MH. WNT5A regulates chondrocyte differentiation through differential use of the CaN/NFAT and IKK/NF-kappaB pathways. Mol Endocrinol. 2010 Aug;24(8):1581-93. doi: 10.1210/me.2010-0037. Epub 2010 Jun 23. PMID: 20573686; PMCID: PMC5417459.
  14. Zheng L, Zhang Z, Sheng P, Mobasheri A. The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis. Ageing Res Rev. 2021 Mar;66:101249. doi: 10.1016/j.arr.2020.101249. Epub 2020 Dec 29. PMID: 33383189.
  15. Xia H, Cao D, Yang F, Yang W, Li W, Liu P, Wang S, Yang F. Jiawei Yanghe decoction ameliorates cartilage degradation in vitro and vivo via Wnt/β-catenin signaling pathway. Biomed Pharmacother. 2020 Feb;122:109708. doi: 10.1016/j.biopha.2019.109708. Epub 2019 Dec 30. PMID: 31918279.
  16. Xu X, Wan Y, Gong L, Ma Z, Xu T. Chinese herbal medicine Yanghe decoction for knee osteoarthritis: A protocol for systematic review and meta-analysis. Medicine (Baltimore). 2020 Aug 21;99(34):e21877. doi: 10.1097/MD.0000000000021877. PMID: 32846845; PMCID: PMC7447488.
  17. Rowan AD, Litherland GJ, Hui W, Milner JM. Metalloproteases as potential therapeutic targets in arthritis treatment. Expert Opin Ther Targets. 2008 Jan;12(1):1-18. doi: 10.1517/14728222.12.1.1. PMID: 18076366.
  18. Özler K, Aktaş E, Atay Ç, Yılmaz B, Arıkan M, Güngör Ş. Serum and knee synovial fluid matrix metalloproteinase-13 and tumor necrosis factor-alpha levels in patients with late-stage osteoarthritis. Acta Orthop Traumatol Turc. 2016;50(3):356-61. doi: 10.3944/AOTT.2015.15.0115. PMID: 27130394.
  19. Hu Q, Ecker M. Overview of MMP-13 as a Promising Target for the Treatment of Osteoarthritis. Int J Mol Sci. 2021 Feb 9;22(4):1742. doi: 10.3390/ijms22041742. PMID: 33572320; PMCID: PMC7916132.
  20. van den Bosch MHJ, van Lent PLEM, van der Kraan PM. Identifying effector molecules, cells, and cytokines of innate immunity in OA. Osteoarthritis Cartilage. 2020 May;28(5):532-543. doi: 10.1016/j.joca.2020.01.016. Epub 2020 Feb 7. PMID: 32044352.
  21. Molnar V, Matišić V, Kodvanj I, Bjelica R, Jeleč Ž, Hudetz D, Rod E, Čukelj F, Vrdoljak T, Vidović D, Starešinić M, Sabalić S, Dobričić B, Petrović T, Antičević D, Borić I, Košir R, Zmrzljak UP, Primorac D. Cytokines and Chemokines Involved in Osteoarthritis Pathogenesis. Int J Mol Sci. 2021 Aug 26;22(17):9208. doi: 10.3390/ijms22179208. PMID: 34502117; PMCID: PMC8431625.
  22. Chen C, Zhang C, Cai L, Xie H, Hu W, Wang T, Lu D, Chen H. Corrigendum to "Baicalin suppresses IL-1β-induced expression of inflammatory cytokines via blocking NF-κB in human osteoarthritis chondrocytes and shows protective effect in mice osteoarthritis models" [Int. Immunopharmacol. 52 (2017) 218-226]. Int Immunopharmacol. 2021 Jun;95:107546. doi: 10.1016/j.intimp.2021.107546. Epub 2021 Mar 16. Erratum for: Int Immunopharmacol. 2017 Nov;52:218-226. doi: 10.1016/j.intimp.2017.09.017. PMID: 33735716.
  23. Shen J, Abu-Amer Y, O'Keefe RJ, McAlinden A. Inflammation and epigenetic regulation in osteoarthritis. Connect Tissue Res. 2017 Jan;58(1):49-63. doi: 10.1080/03008207.2016.1208655. Epub 2016 Jul 7. PMID: 27389927; PMCID: PMC5266560.
  24. Wang C, Al-Ani MK, Sha Y, Chi Q, Dong N, Yang L, Xu K. Psoralen Protects Chondrocytes, Exhibits Anti-Inflammatory Effects on Synoviocytes, and Attenuates Monosodium Iodoacetate-Induced Osteoarthritis. Int J Biol Sci. 2019 Jan 1;15(1):229-238. doi: 10.7150/ijbs.28830. PMID: 30662362; PMCID: PMC6329921.
  25. Leong DJ, Li YH, Gu XI, Sun L, Zhou Z, Nasser P, Laudier DM, Iqbal J, Majeska RJ, Schaffler MB, Goldring MB, Cardoso L, Zaidi M, Sun HB. Physiological loading of joints prevents cartilage degradation through CITED2. FASEB J. 2011 Jan;25(1):182-91. doi: 10.1096/fj.10-164277. Epub 2010 Sep 8. PMID: 20826544; PMCID: PMC3005439.
  26. Zhang Y, Li R, Zhong Y, Zhang S, Zhou L, Shang S. Fuyuan Decoction Enhances SOX9 and COL2A1 Expression and Smad2/3 Phosphorylation in IL-1β-Activated Chondrocytes. Evid Based Complement Alternat Med. 2015;2015:821947. doi: 10.1155/2015/821947. Epub 2015 Dec 7. PMID: 26770254; PMCID: PMC4685114.
  27. Grodzinsky AJ, Levenston ME, Jin M, Frank EH. Cartilage tissue remodeling in response to mechanical forces. Annu Rev Biomed Eng. 2000;2:691-713. doi: 10.1146/annurev.bioeng.2.1.691. PMID: 11701528.
  28. Wilkinson DJ, Desilets A, Lin H, Charlton S, Del Carmen Arques M, Falconer A, Bullock C, Hsu YC, Birchall K, Hawkins A, Thompson P, Ferrell WR, Lockhart J, Plevin R, Zhang Y, Blain E, Lin SW, Leduc R, Milner JM, Rowan AD. The serine proteinase hepsin is an activator of pro-matrix metalloproteinases: molecular mechanisms and implications for extracellular matrix turnover. Sci Rep. 2017 Dec 1;7(1):16693. doi: 10.1038/s41598-017-17028-3. PMID: 29196708; PMCID: PMC5711915.
  29. Wilkinson DJ, Arques MDC, Huesa C, Rowan AD. Serine proteinases in the turnover of the cartilage extracellular matrix in the joint: implications for therapeutics. Br J Pharmacol. 2019 Jan;176(1):38-51. doi: 10.1111/bph.14173. Epub 2018 Mar 30. PMID: 29473950; PMCID: PMC6284380.
  30. de Mezer M, Rogaliński J, Przewoźny S, Chojnicki M, Niepolski L, Sobieska M, Przystańska A. SERPINA3: Stimulator or Inhibitor of Pathological Changes. Biomedicines. 2023 Jan 7;11(1):156. doi: 10.3390/biomedicines11010156. PMID: 36672665; PMCID: PMC9856089.
  31. Baker C, Belbin O, Kalsheker N, Morgan K. SERPINA3 (aka alpha-1-antichymotrypsin). Front Biosci. 2007 May 1;12:2821-35. doi: 10.2741/2275. PMID: 17485262.
  32. Wilkinson DJ. Serpins in cartilage and osteoarthritis: what do we know? Biochem Soc Trans. 2021 Apr 30;49(2):1013-1026. doi: 10.1042/BST20201231. PMID: 33843993; PMCID: PMC8106492.
  33. Fang W, Song Q, Lv T, Lv J, Cai Z, Wang Z, Song X, Ji X, Huang J. Serpina3n/serpina3 alleviates cyclophosphamide-induced interstitial cystitis by activating the Wnt/β-catenin signal. Int Urol Nephrol. 2023 Dec;55(12):3065-3075. doi: 10.1007/s11255-023-03726-7. Epub 2023 Aug 18. PMID: 37594700; PMCID: PMC10611603.
  34. Ajekigbe B, Cheung K, Xu Y, Skelton AJ, Panagiotopoulos A, Soul J, Hardingham TE, Deehan DJ, Barter MJ, Young DA. Identification of long non-coding RNAs expressed in knee and hip osteoarthritic cartilage. Osteoarthritis Cartilage. 2019 Apr;27(4):694-702. doi: 10.1016/j.joca.2018.12.015. Epub 2019 Jan 3. PMID: 30611906; PMCID: PMC6444060.
  35. Liu Z, Liu R, Wang R, Dai J, Chen H, Wang J, Li X. Sinensetin attenuates IL-1β-induced cartilage damage and ameliorates osteoarthritis by regulating SERPINA3. Food Funct. 2022 Oct 3;13(19):9973-9987. doi: 10.1039/d2fo01304e. PMID: 36056701.
  36. Tian S, Peng P, Li J, Deng H, Zhan N, Zeng Z, Dong W. SERPINH1 regulates EMT and gastric cancer metastasis via the Wnt/β-catenin signaling pathway. Aging (Albany NY). 2020 Feb 24;12(4):3574-3593. doi: 10.18632/aging.102831. Epub 2020 Feb 24. PMID: 32091407; PMCID: PMC7066881.
  37. Zhang B, Abreu JG, Zhou K, Chen Y, Hu Y, Zhou T, He X, Ma JX. Blocking the Wnt pathway, a unifying mechanism for an angiogenic inhibitor in the serine proteinase inhibitor family. Proc Natl Acad Sci U S A. 2010 Apr 13;107(15):6900-5. doi: 10.1073/pnas.0906764107. Epub 2010 Mar 29. PMID: 20351274; PMCID: PMC2872418.
  38. Xu Q , Fan Y , Loor JJ , Liang Y , Lv H , Sun X , Jia H , Xu C . Aloin protects mice from diet-induced non-alcoholic steatohepatitis via activation of Nrf2/HO-1 signaling. Food Funct. 2021 Jan 21;12(2):696-705. doi: 10.1039/d0fo02684k. Epub 2021 Jan 7. PMID: 33410857.
  39. Ma Y, Tang T, Sheng L, Wang Z, Tao H, Zhang Q, Zhang Y, Qi Z. Aloin suppresses lipopolysaccharide‑induced inflammation by inhibiting JAK1‑STAT1/3 activation and ROS production in RAW264.7 cells. Int J Mol Med. 2018 Oct;42(4):1925-1934. doi: 10.3892/ijmm.2018.3796. Epub 2018 Jul 31. PMID: 30066904; PMCID: PMC6108888.
  40. Dalbeth N, Lauterio TJ, Wolfe HR. Mechanism of action of colchicine in the treatment of gout. Clin Ther. 2014 Oct 1;36(10):1465-79. doi: 10.1016/j.clinthera.2014.07.017. Epub 2014 Aug 21. PMID: 25151572.
  41. Takeuchi K, Ogawa H, Kuramitsu N, Akaike K, Goto A, Aoki H, Lassar A, Suehara Y, Hara A, Matsumoto K, Akiyama H. Colchicine protects against cartilage degeneration by inhibiting MMP13 expression via PLC-γ1 phosphorylation. Osteoarthritis Cartilage. 2021 Nov;29(11):1564-1574. doi: 10.1016/j.joca.2021.08.001. Epub 2021 Aug 20. PMID: 34425229; PMCID: PMC8542595.
  42. Zhang C, Shao Z, Hu X, Chen Z, Li B, Jiang R, Bsoul N, Chen J, Xu C, Gao W. Inhibition of PI3K/Akt/NF-κB signaling by Aloin for ameliorating the progression of osteoarthritis: In vitro and in vivo studies. Int Immunopharmacol. 2020 Dec;89(Pt B):107079. doi: 10.1016/j.intimp.2020.107079. Epub 2020 Oct 20. PMID: 33096361.
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