Matrine is an active ingredient in traditional Chinese medicine that has been shown to be effective in treating bone disorders. The anti-osteoarthritis (OA) effects of matrine were assessed using both in in vitro and in vivo systems, and the mechanisms underlying the effects were investigated by focusing on the activity of miR-29b-3p/PGRN axis. The miR was chosen as potential target for matrine after chondrocytes were treated with both IL-1? and matrine. Changes in cell viability, cell apoptosis, inflammation, and miR-29b-3p/PGRN axis were detected. In vitro assays results were validated using collagen-induced arthritis (CIA) rat models. Incubation with IL-1? reduced cell viability, induced cell apoptosis, and inhibited production of cytokines in chondrocytes, which was associated with the up-regulation of miR-29b-3p and down-regulation of PGRN. In CIA rats, matrine reduced bone destruction and weight loss in a dose-dependent manner. Matrine also reduced the systemic levels of cytokines. At the molecular level, matrine inhibited the expression of miR-29b-3p while increasing the expression of PGRN. The findings outlined in the current study showed that matrine exerted its anti-OA effects by modulating the miR-29b-3p/PGRN axis.

Department of Joint Surgery The Affiliated Hospital of Medical School Ningbo University Ningbo Zhejiang China

See more in PubMed

Loeser RF, Collins JA, Diekman BO. Ageing and the pathogenesis of osteoarthritis. Nat Rev Rheumatol. 2016;12:412–420. doi: 10.1038/nrrheum.2016.65. PubMed DOI PMC

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;32:3854–3860. doi: 10.1016/j.arth.2017.07.021. PubMed DOI

Abouheif MM, Nakasa T, Shibuya H, Niimoto T, Kongcharoensombat W, Ochi M. Silencing microRNA-34a inhibits chondrocyte apoptosis in a rat osteoarthritis model in vitro. Rheumatology (Oxford) 2010;49:2054–2060. doi: 10.1093/rheumatology/keq247. PubMed DOI

Li J, Huang J, Dai L, Yu D, Chen Q, Zhang X, et al. miR-146a, an IL-1β responsive miRNA, induces vascular endothelial growth factor and chondrocyte apoptosis by targeting Smad4. Arthritis Res Ther. 2012;14:R75. doi: 10.1186/ar3798. PubMed DOI PMC

Le LT, Swingler TE, Crowe N, Vincent TL, Barter MJ, Donell ST, et al. The microRNA-29 family in cartilage homeostasis and osteoarthritis. J Mol Med (Berl) 2016;94:583–596. doi: 10.1007/s00109-015-1374-z. PubMed DOI PMC

Bobinac D, Spanjol J, Zoricic S, Maric I. Changes in articular cartilage and subchondral bone histomorphometry in osteoarthritic knee joints in humans. Bone. 2003;32:284–290. doi: 10.1016/S8756-3282(02)00982-1. PubMed DOI

Wang B, Zhong JL, Xu XH, Wu B, Shang J, Jiang N, et al. Gene expression profiling analysis to identify key genes and underlying mechanisms in meniscus of osteoarthritis patients. Comb Chem High Throughput Screen. 2021;24:1151–1167. doi: 10.2174/1386207323666200902140656. PubMed DOI

Wang X, Guo Y, Wang C, Yu H, Yu X, Yu H. MicroRNA-142-3p Inhibits chondrocyte apoptosis and inflammation in osteoarthritis by targeting HMGB1. Inflammation. 2016;39:1718–1728. doi: 10.1007/s10753-016-0406-3. PubMed DOI

Zhang Y, Jia J, Yang S, Liu X, Ye S, Tian H. MicroRNA-21 controls the development of osteoarthritis by targeting GDF-5 in chondrocytes. Exp Mol Med. 2014;46:e79. doi: 10.1038/emm.2013.152. PubMed DOI PMC

Song J, Kim D, Lee CH, Lee MS, Chun CH, Jin EJ. MicroRNA-488 regulates zinc transporter SLC39A8/ZIP8 during pathogenesis of osteoarthritis. J Biomed Sci. 2013;20:31. doi: 10.1186/1423-0127-20-31. PubMed DOI PMC

Wang Y, Guo X, Fan X, Zhang H, Xue D, Pan Z. The protective effect of mangiferin on osteoarthritis: An in vitro and in vivo study. Physiol Res. 2022;71:135–145. doi: 10.33549/physiolres.934747. PubMed DOI PMC

Wang DD, Wu XY, Dong JY, Cheng XP, Gu SF, Olatunji OJ, et al. Qing-Luo-Yin Alleviated experimental arthritis in rats by disrupting immune feedback between inflammatory T cells and monocytes: key evidences from its effects on immune cell phenotypes. J Inflamm Res. 2021;14:7467–7486. doi: 10.2147/JIR.S346365. PubMed DOI PMC

Pu J, Fang FF, Li XQ, Shu ZH, Jiang YP, Han T, et al. Matrine exerts a strong anti-arthritic effect on type II collagen-induced arthritis in rats by inhibiting inflammatory responses. Int J Mol Sci. 2016:17. doi: 10.3390/ijms17091410. PubMed DOI PMC

Yang Y, Dong Q, Li R. Matrine induces the apoptosis of fibroblast-like synoviocytes derived from rats with collagen-induced arthritis by suppressing the activation of the JAK/STAT signaling pathway. Int J Mol Med. 2017;39:307–316. doi: 10.3892/ijmm.2016.2843. PubMed DOI PMC

Niu Y, Dong Q, Li R. Matrine regulates Th1/Th2 cytokine responses in rheumatoid arthritis by attenuating the NF-κB signaling. Cell Biol Int. 2017;41:611–621. doi: 10.1002/cbin.10763. PubMed DOI

Chen L, Li Q, Wang J, Jin S, Zheng H, Lin J, et al. MiR-29b-3p promotes chondrocyte apoptosis and facilitates the occurrence and development of osteoarthritis by targeting PGRN. J Cell Mol Med. 2017;21:3347–3359. doi: 10.1111/jcmm.13237. PubMed DOI PMC

Zhi L, Zhao J, Zhao H, Qing Z, Liu H, Ma J. Downregulation of LncRNA OIP5-AS1 Induced by IL-1β aggravates osteoarthritis via regulating miR-29b-3p/PGRN. Cartilage. 2021;13(Suppl 2):1345s–55s. doi: 10.1177/1947603519900801. PubMed DOI PMC

Wu J, Zhang H, Deng R, Xing L, Hu M, Fu X. Interleukin-Iβ promotes cartilage degeneration by regulating forkhead box protein O4 and type II collagen. Mol Med Rep. 2021;24(5) doi: 10.3892/mmr.2021.12453. PubMed DOI PMC

Wang SN, Xie GP, Qin CH, Chen YR, Zhang KR, Li X, et al. Aucubin prevents interleukin-1 beta induced inflammation and cartilage matrix degradation via inhibition of NF-κB signaling pathway in rat articular chondrocytes. Int Immunopharmacol. 2015;24:408–415. doi: 10.1016/j.intimp.2014.12.029. PubMed DOI

Li X, Zhang L, Xu Y, Zhao D, Mu L, Zhang B, et al. Therapeutic effect of matrine on collagen-induced arthritis rats and its regulatory effect on RANKL and OPG expression. J Immunol Res. 2021;2021:4186102. doi: 10.1155/2021/4186102. PubMed DOI PMC

Zheng CJ, Zhao XX, Ai HW, Lin B, Han T, Jiang YP, et al. Therapeutic effects of standardized Vitex negundo seeds extract on complete Freund’s adjuvant induced arthritis in rats. Phytomedicine. 2014;21:838–846. doi: 10.1016/j.phymed.2014.02.003. PubMed DOI

Choi JK, Oh HM, Park JH, Choi JH, Sa KH, Kang YM, et al. Salvia plebeia extract inhibits the inflammatory response in human rheumatoid synovial fibroblasts and a murine model of arthritis. Phytomedicine. 2015;22:415–422. doi: 10.1016/j.phymed.2015.01.007. PubMed DOI

Zhang H, Chen L, Sun X, Yang Q, Wan L, Guo C. Matrine: A promising natural product with various pharmacological activities. Front Pharmacol. 2020;11:588. doi: 10.3389/fphar.2020.00588. PubMed DOI PMC

Wang S, Lian X, Sun M, Luo L, Guo L. Efficacy of compound Kushen injection plus radiotherapy on nonsmall-cell lungcancer: A systematic review and meta-analysis. J Cancer Res Ther. 2016;12:1298–1306. doi: 10.4103/0973-1482.199538. PubMed DOI

Yu L, Zhou Y, Yang Y, Lu F, Fan Y. Efficacy and Safety of Compound Kushen Injection on Patients with Advanced Colon Cancer: A meta-analysis of randomized controlled trials. Evid Based Complement Alternat Med. 2017;2017:7102514. doi: 10.1155/2017/7102514. PubMed DOI PMC

Yang H, Xie Y, Ni J, Liu Y, Song R, Chen C, et al. Association rule analysis for validating interrelationships of combined medication of compound kushen injection in treating colon carcinoma: a hospital information system-based real-world study. Evid Based Complement Alternat Med. 2018;2018:4579801. doi: 10.1155/2018/4579801. PubMed DOI PMC

Tian R, Li Y, Yao X. PGRN Suppresses inflammation and promotes autophagy in keratinocytes through the Wnt/β-catenin signaling pathway. Inflammation. 2016;39:1387–1394. doi: 10.1007/s10753-016-0370-y. PubMed DOI

Daniel R, He Z, Carmichael KP, Halper J, Bateman A. Cellular localization of gene expression for progranulin. J Histochem Cytochem. 2000;48:999–1009. doi: 10.1177/002215540004800713. PubMed DOI

He Z, Ong CH, Halper J, Bateman A. Progranulin is a mediator of the wound response. Nat Med. 2003;9:225–229. doi: 10.1038/nm816. PubMed DOI

Serrero G, Hawkins DM, Yue B, Ioffe O, Bejarano P, Phillips JT, et al. Progranulin (GP88) tumor tissue expression is associated with increased risk of recurrence in breast cancer patients diagnosed with estrogen receptor positive invasive ductal carcinoma. Breast Cancer Res. 2012;14:R26. doi: 10.1186/bcr3111. PubMed DOI PMC

Yin F, Dumont M, Banerjee R, Ma Y, Li H, Lin MT, et al. Behavioral deficits and progressive neuropathology in progranulin-deficient mice: a mouse model of frontotemporal dementia. Faseb J. 2010;24:4639–4647. doi: 10.1096/fj.10-161471. PubMed DOI PMC