• This record comes from PubMed

Baicalin Ameliorates Cartilage Injury in Rats With Osteoarthritis via Modulating miR-766-3p/AIFM1 Axis

. 2024 Aug 31 ; 73 (4) : 633-642.

Language English Country Czech Republic Media print

Document type Journal Article

The study aims to elucidate the therapeutic mechanism of Baicalin (BAI) in alleviating cartilage injury in osteoarthritic (OA) rat models, concentrating on its regulation of the miR-766-3p/AIFM1 axis. An OA rat model was developed with unilateral anterior cruciate ligament transection (ACLT). Interventions comprised of BAI treatment and intra-articular administration of miR-766-3p inhibitor. For evaluation, histopathological staining was conducted to investigate the pathological severity of knee cartilage injury. The levels of oxidative stress (OS) indicators including MDA, SOD, and GSH-Px, were quantified using colorimetric assays. Inflammatory factors (IFs; TNF-?, IL-1?, and IL-6) in knee joint lavage fluids were assessed using ELISA, while RT-PCR was employed to quantify miR-766-3p expression. TUNEL apoptosis staining was utilized to detect chondrocyte apoptosis, and western blotting examined autophagy-related markers (LC3, Beclin, p62), extracellular matrix (ECM) synthesis-associated indices (COL2A, ACAN, MMP13), and apoptosis-inducing factor mitochondrion-associated 1 (AIFM1). Histological examination revealed a marked amelioration of cartilage injury in the BAI-treated OA rat models compared to controls. BAI treatment significantly reduced inflammation and OS of knee joint fluid, activated autophagy, and decreased chondrocyte apoptosis and ECM degradation. Interestingly, the inhibitory effects of BAI on these pathological markers were significantly decreased by the miR-766-3p inhibitor. Further assessment revealed that BAI efficiently promoted miR-766-3p expression while inhibiting AIFM1 protein expression. BAI potentially mitigates articular cartilage injury in OA rats, likely through modulation of miR-766-3p/AIFM1 axis. Keywords: Baicalin, microRNA, AIFM1, Osteoarthritisv, Rat.

See more in PubMed

Sharma L. Osteoarthritis of the knee. New England J Med. 2021;384:51–59. doi: 10.1056/NEJMcp1903768. PubMed DOI

Schram B, Orr R, Pope R, et al. Risk factors for development of lower limb osteoarthritis in physically demanding occupations: A narrative umbrella review. Journal of occupational health. 2020;62:e12103. doi: 10.1002/1348-9585.12103. PubMed DOI PMC

Vos T, Lim SS, Abbafati C, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396:1204–1222. doi: 10.1016/S0140-6736(20)30925-9. PubMed DOI PMC

March L, Smith EUR, Hoy DG, et al. Burden of disability due to musculoskeletal (MSK) disorders. Best practice & research Clinical rheumatology. 2014;28:353–366. doi: 10.1016/j.berh.2014.08.002. PubMed DOI

Vincent TL. Targeting mechanotransduction pathways in osteoarthritis: a focus on the pericellular matrix. Current opinion in pharmacology. 2013;13:449–454. doi: 10.1016/j.coph.2013.01.010. PubMed DOI

Lee W, Ku SK, Bae JS. Anti-inflammatory effects of Baicalin, Baicalein, and Wogonin in vitro and in vivo. Inflammation, 2015;38:110–125. doi: 10.1007/s10753-014-0013-0. PubMed DOI

Duan X, Guo G, Pei X, et al. Baicalin inhibits cell viability, migration and invasion in breast cancer by regulating miR-338–3p and MORC4. OncoTargets Therap. 2019;12:11183. doi: 10.2147/OTT.S217101. PubMed DOI PMC

Wang X, Yu J, Sun Y, et al. Baicalin protects LPS-induced blood-brain barrier damage and activates Nrf2-mediated antioxidant stress pathway. Int Immunopharmacol. 2021;96:107725. doi: 10.1016/j.intimp.2021.107725. PubMed DOI

Hu S, Jiang L, Yan Q, et al. Evidence construction of baicalin for treating myocardial ischemia diseases: A preclinical meta-analysis. Phytomedicine. 2022;107:154476. doi: 10.1016/j.phymed.2022.154476. PubMed DOI

Wang X, Xie L, Long J, et al. Therapeutic effect of baicalin on inflammatory bowel disease: A review. J Ethnopharmacol. 2022;283:114749. doi: 10.1016/j.jep.2021.114749. PubMed DOI

Li B, Chen K, Qian N, et al. Baicalein alleviates osteoarthritis by protecting subchondral bone, inhibiting angiogenesis and synovial proliferation. J Cell Mol Med. 2021;25:5283–5294. doi: 10.1111/jcmm.16538. PubMed DOI PMC

Dinda B, Dinda S, DasSharma S, et al. Therapeutic potentials of baicalin and its aglycone, baicalein against inflammatory disorders. Eur J Med Chem. 2017;131:68–80. doi: 10.1016/j.ejmech.2017.03.004. PubMed DOI

Ding W, Du D, Chen S. LIPUS promotes synthesis and secretion of extracellular matrix and reduces cell apoptosis in human osteoarthritis through upregulation of SOX9 expression. Int J Clin Exp Pathol. 2020;13:810. PubMed PMC

Chen C, Zhang C, Cai L, et al. 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. 2017;52:218–226. doi: 10.1016/j.intimp.2017.09.017. PubMed DOI

You Y, Que K, Zhou Y, et al. MicroRNA-766-3p inhibits tumour progression by targeting Wnt3a in hepatocellular carcinoma. Mol Cells. 2018;41:830. PubMed PMC

Oh K, Lee DS. In vivo validation of metastasis-regulating microRNA-766 in human triple-negative breast cancer cells. Laboratory Animal Research. 2017;33:256–263. doi: 10.5625/lar.2017.33.3.256. PubMed DOI PMC

Li Z, Cheng J, Liu J. Baicalin protects human OA chondrocytes against IL-1β-induced apoptosis and ECM degradation by activating autophagy via MiR-766-3p/AIFM1 axis. Drug Design, Development and Therapy. 2020:2645–2655. doi: 10.2147/DDDT.S255823. PubMed DOI PMC

Cui L, Feng L, Zhang ZH, Jia XB. The anti-inflammation effect of baicalin on experimental colitis through inhibiting TLR4/NF-kappaB pathway activation. Int Immunopharmacol. 2014;23:294–303. doi: 10.1016/j.intimp.2014.09.005. PubMed DOI

Khan NM, Ahmad I, Haqqi TM. Nrf2/ARE pathway attenuates oxidative and apoptotic response in human osteoarthritis chondrocytes by activating ERK1/2/ELK1-P70S6K-P90RSK signaling axis. Free Radic Biol Med. 2018;116:159–171. doi: 10.1016/j.freeradbiomed.2018.01.013. PubMed DOI PMC

Li Y, Wu Y, Jiang K, et al. Mangiferin prevents TBHP-induced apoptosis and ECM degradation in mouse osteoarthritic chondrocytes via restoring autophagy and ameliorates murine osteoarthritis. Oxid Med Cell Longev. 2019;2019:8783197. doi: 10.1155/2019/8783197. PubMed DOI PMC

Yang X, Zhang Q, Gao Z, Yu C, Zhang L. Baicalin alleviates IL-1β-induced inflammatory injury via down-regulating miR-126 in chondrocytes. Biomed Pharmacother. 2018;99:184–190. doi: 10.1016/j.biopha.2018.01.041. PubMed DOI

Chen D-S, Cao J-G, Zhu B, Wang Z-L, Wang T-F, Tang J-J. Baicalin attenuates joint pain and muscle dysfunction by inhibiting muscular oxidative stress in an experimental osteoarthritis rat model. Arch Immunol Ther Exp. 2018;66:453–461. doi: 10.1007/s00005-018-0518-6. PubMed DOI

Kapoor M, Martel-Pelletier J, Lajeunesse D, Pelletier JP, Fahmi H. Role of proinflammatory cytokines in the pathophysiology of osteoarthritis. Nat Rev Rheumatol. 2011;7:33–42. doi: 10.1038/nrrheum.2010.196. PubMed DOI

Daheshia M, Yao JQ. The interleukin 1β pathway in the pathogenesis of osteoarthritis. J Rheumatol. 2008;35:2306–2312. doi: 10.3899/jrheum.080346. PubMed DOI

Hussein MR, Fathi NA, El-Din AME, et al. Alterations of the CD4+, CD8+ T cell subsets, Interleukins-1β, IL-10, IL-17, tumor necrosis Factor-α and soluble intercellular adhesion molecule-1 in rheumatoid arthritis and osteoarthritis: preliminary observations. Pathol Oncol Res. 2008;14:321–328. doi: 10.1007/s12253-008-9016-1. PubMed DOI

Mizushima N. Physiological functions of autophagy. Curr Top Microbiol Immunol. 2009;335:71–84. doi: 10.1007/978-3-642-00302-8_3. PubMed DOI

Caramés B, Taniguchi N, Otsuki S, Blanco FJ, Lotz M. Autophagy is a protective mechanism in normal cartilage, and its aging-related loss is linked with cell death and osteoarthritis. Arthritis Rheum. 2010;62:791–801. doi: 10.1002/art.27305. PubMed DOI PMC

Saberi Hosnijeh F, Bierma-Zeinstra SM, Bay-Jensen AC. Osteoarthritis year in review 2018: biomarkers (biochemical markers) Osteoarthr Cartil. 2019;27:412–423. doi: 10.1016/j.joca.2018.12.002. PubMed DOI

Wang X, Li M, Hu Y. miR-29c-3p Attenuates beta-Amyloid-Induced Neurotoxicity in Alzheimer’s Disease Through Regulating beta-Site Amyloid Precursor Protein-Cleaving Enzyme 1. Physiol Res. 2023;72:833–841. doi: 10.33549/physiolres.935084. PubMed DOI PMC

Zhu B, He J, Ye X, Pei X, Bai Y, Gao F, Guo L, Yong H, Zhao W. Role of Cisplatin in Inducing Acute Kidney Injury and Pyroptosis in Mice via the Exosome miR-122/ELAVL1 Regulatory Axis. Physiol Res. 2023;31(72):753–765. doi: 10.33549/physiolres.935129. PubMed DOI PMC

Le LT, Swingler TE, Clark IM. Review: the role of microRNAs in osteoarthritis and chondrogenesis. Arthritis Rheum. 2013;65:1963–1974. doi: 10.1002/art.37990. PubMed DOI

Iliopoulos D, Malizos KN, Oikonomou P, Tsezou A. Integrative microRNA and proteomic approaches identify novel osteoarthritis genes and their collaborative metabolic and inflammatory networks. PLoS One. 2008;3:e3740. doi: 10.1371/journal.pone.0003740. PubMed DOI PMC

Sharma A, Diecke S, Zhang WY, et al. The role of SIRT6 protein in aging and reprogramming of human induced pluripotent stem cells. J Biol Chem. 2013;288:18439–18447. doi: 10.1074/jbc.M112.405928. PubMed DOI PMC

Find record

Citation metrics

Loading data ...

Archiving options

Loading data ...