MiR-539-3p Alleviates Apoptosis and Extracellular Matrix Degradation in Chondrocytes of Childhood-Onset Osteoarthritis by Targeting RUNX2
Jazyk angličtina Země Česko Médium print
Typ dokumentu časopisecké články
PubMed
39027958
PubMed Central
PMC11299779
DOI
10.33549/physiolres.935291
PII: 935291
Knihovny.cz E-zdroje
- MeSH
- apoptóza * MeSH
- chondrocyty * metabolismus patologie MeSH
- dítě MeSH
- extracelulární matrix * metabolismus patologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- mikro RNA * metabolismus genetika MeSH
- mladiství MeSH
- osteoartróza * metabolismus patologie genetika MeSH
- protein PEBP2alfaA * metabolismus genetika MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- mikro RNA * MeSH
- protein PEBP2alfaA * MeSH
- RUNX2 protein, human MeSH Prohlížeč
Recent research has identified that miR-539-3p impedes chondrogenic differentiation, yet its specific role and underlying mechanisms in childhood-onset osteoarthritis (OA) remain unclear. This study found that miR-539-3p levels were considerably lower in cartilage samples derived from childhood-onset OA patients compared to the control group. Enhancing miR-539-3p expression or suppressing RUNX2 expression notably reduced apoptosis, inflammation, and extracellular matrix (ECM) degradation in OA chondrocytes. In contrast, reducing miR-539-3p or increasing RUNX2 had the opposite effects. RUNX2 was confirmed as a direct target of miR-539-3p. Further experiments demonstrated that miR-539-3p targeting RUNX2 effectively lessened apoptosis, inflammation, and ECM degradation in OA chondrocytes, accompanied by changes in key molecular markers like reduced caspase-3 and matrix etallopeptidase 13 (MMP-13) levels, and increased B-cell lymphoma 2 (Bcl-2) and collagen type X alpha 1 chain (COL2A1). This study underscores the pivotal role of miR-539-3p in alleviating inflammation and ECM degradation in childhood-onset OA through targeting RUNX2, offering new insights for potential therapeutic strategies against this disease.
Zobrazit více v PubMed
Ondresik M, Azevedo Maia FR, da Silva Morais A, Gertrudes AC, Dias Bacelar AH, Correia C, Goncalves C, et al. Management of knee osteoarthritis. Current status and future trends. Biotechnol Bioeng. 2017;114:717–739. doi: 10.1002/bit.26182. PubMed DOI
Caine DJ, Golightly YM. Osteoarthritis as an outcome of paediatric sport: an epidemiological perspective. Br J Sports Med. 2011;45:298–303. doi: 10.1136/bjsm.2010.081984. PubMed DOI
Boehme KA, Rolauffs B. Onset and Progression of Human Osteoarthritis-Can Growth Factors, Inflammatory Cytokines, or Differential miRNA Expression Concomitantly Induce Proliferation, ECM Degradation, and Inflammation in Articular Cartilage? Int J Mol Sci. 2018;19:2282. doi: 10.3390/ijms19082282. PubMed DOI PMC
Zamli Z, Adams MA, Tarlton JF, Sharif M. Increased chondrocyte apoptosis is associated with progression of osteoarthritis in spontaneous Guinea pig models of the disease. Int J Mol Sci. 2013;14:17729–17743. doi: 10.3390/ijms140917729. PubMed DOI PMC
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. doi: 10.1016/j.bcp.2019.02.036. PubMed DOI
Wang J, Liu S, Shi J, Li J, Wang S, Liu H, Zhao S, Duan K, Pan X, Yi Z. The Role of miRNA in the Diagnosis, Prognosis, and Treatment of Osteosarcoma. Cancer Biother Radiopharm. 2019;34:605–613. doi: 10.1089/cbr.2019.2939. PubMed DOI
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
Jones SW, Watkins G, Le Good N, Roberts S, Murphy CL, Brockbank SM, Needham MR, et al. The identification of differentially expressed microRNA in osteoarthritic tissue that modulate the production of TNF-alpha and MMP13. Osteoarthritis Cartilage. 2009;17:464–472. doi: 10.1016/j.joca.2008.09.012. PubMed DOI
Zhang W, Hu C, Zhang C, Luo C, Zhong B, Yu X. MiRNA-132 regulates the development of osteoarthritis in correlation with the modulation of PTEN/PI3K/AKT signaling. BMC Geriatr. 2021;21:175. doi: 10.1186/s12877-021-02046-8. PubMed DOI PMC
Wang H, Wang W, Wang J, Zhang L, Luo Y, Tang X. MicroRNA-15a/beta1,4-GalT-I axis contributes to cartilage degeneration via NF-kappaB signaling in osteoarthritis. Clinics (Sao Paulo) 2023;78:100254. doi: 10.1016/j.clinsp.2023.100254. PubMed DOI PMC
Sun Y, Su S, Li M, Deng A. Inhibition of miR-182-5p Targets FGF9 to Alleviate Osteoarthritis. Anal Cell Pathol (Amst) 2023;2023:5911546. doi: 10.1155/2023/5911546. PubMed DOI PMC
Zhou J, Su M, Zhang H, Wang J, Chen Y. miR-539-3P inhibits proliferation and invasion of gastric cancer cells by targeting CTBP1. Int J Clin Exp Pathol. 2019;12:1618–1625. PubMed PMC
Wang Z, Hu T, Jin C, Yu J, Zhu D, Liu J. The anti-tumor effect of miR-539-3p on colon cancer via regulating cell viability, motility, and nude mouse tumorigenicity with CDK14 inhibition. J Gastrointest Oncol. 2020;11:899–910. doi: 10.21037/jgo-20-387. PubMed DOI PMC
Gong YB, Fan XH. MiR-539-3p promotes the progression of epithelial ovarian cancer by targeting SPARCL1. Eur Rev Med Pharmacol Sci. 2019;23:2366–2373. doi: 10.26355/eurrev_201903_17381. PubMed DOI
Yang Z, Hao J, Hu ZM. MicroRNA expression profiles in human adipose-derived stem cells during chondrogenic differentiation. Int J Mol Med. 2015;35:579–586. doi: 10.3892/ijmm.2014.2051. PubMed DOI PMC
Qin F, Wang F, Wang XP, Chen J, Zeng FH, Sun CL, Mao JP, Li CL. MiR-539-3p inhibited chondrogenic differentiation in human adipose stem cells by targeting Sox9. J Orthop Surg Res. 2022;17:168. doi: 10.1186/s13018-022-03053-0. PubMed DOI PMC
Kim IS, Otto F, Zabel B, Mundlos S. Regulation of chondrocyte differentiation by Cbfa1. Mech Dev. 1999;80:159–170. doi: 10.1016/S0925-4773(98)00210-X. PubMed DOI
Zheng Q, Zhou G, Morello R, Chen Y, Garcia-Rojas X, Lee B. Type X collagen gene regulation by Runx2 contributes directly to its hypertrophic chondrocyte-specific expression in vivo. J Cell Biol. 2003;162:833–842. doi: 10.1083/jcb.200211089. PubMed DOI PMC
Hirata M, Kugimiya F, Fukai A, Saito T, Yano F, Ikeda T, Mabuchi A, et al. C/EBPbeta and RUNX2 cooperate to degrade cartilage with MMP-13 as the target and HIF-2alpha as the inducer in chondrocytes. Hum Mol Genet. 2012;21:1111–1123. doi: 10.1093/hmg/ddr540. PubMed DOI
Kamekura S, Kawasaki Y, Hoshi K, Shimoaka T, Chikuda H, Maruyama Z, Komori T, et al. Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability. Arthritis Rheum. 2006;54:2462–2470. doi: 10.1002/art.22041. PubMed DOI
Wang Y, Zheng X, Luo D, Xu W, Zhou X. MiR-99a alleviates apoptosis and extracellular matrix degradation in experimentally induced spine osteoarthritis by targeting FZD8. BMC Musculoskelet Disord. 2022;23:872. doi: 10.1186/s12891-022-05822-8. PubMed DOI PMC
Pritzker KP, Gay S, Jimenez SA, Ostergaard K, Pelletier JP, Revell PA, Salter D, van den Berg WB. Osteoarthritis cartilage histopathology: grading and staging. Osteoarthritis Cartilage. 2006;14:13–29. doi: 10.1016/j.joca.2005.07.014. PubMed DOI
Zhang Z, Zhao T, Xu H, Wu X. Circ_0008365 Suppresses Apoptosis, Inflammation and Extracellular Matrix Degradation of IL-1beta-treated Chondrocytes in Osteoarthritis by Regulating miR-324-5p/BMPR2/NF-kappaB Signaling Axis. Immunol Invest. 2022;51:1598–1611. doi: 10.1080/08820139.2021.2001496. PubMed DOI
Miyaki S, Asahara H. Macro view of microRNA function in osteoarthritis. Nat Rev Rheumatol. 2012;8:543–552. doi: 10.1038/nrrheum.2012.128. PubMed DOI PMC
Liu Y, Qian K, Li C, Ma Y, Chen X. Roles of microRNA-539 and osteopontin in rheumatoid arthritis. Exp Ther Med. 2018;15:2681–2687. doi: 10.3892/etm.2017.5665. PubMed DOI PMC
Peng Y, Jiang H, Zuo HD. Factors affecting osteogenesis and chondrogenic differentiation of mesenchymal stem cells in osteoarthritis. World J Stem Cells. 2023;15:548–560. doi: 10.4252/wjsc.v15.i6.548. PubMed DOI PMC
Hu X, Miao H. MiR-539-5p inhibits the inflammatory injury in septic H9c2 cells by regulating IRAK3. Mol Biol Rep. 2022;49:121–130. doi: 10.1007/s11033-021-06849-1. PubMed DOI PMC
Meng L, Cao H, Wan C, Jiang L. MiR-539-5p alleviates sepsis-induced acute lung injury by targeting ROCK1. Folia Histochem Cytobiol. 2019;57:168–178. doi: 10.5603/FHC.a2019.0019. PubMed DOI
Martel-Pelletier J, Boileau C, Pelletier JP, Roughley PJ. Cartilage in normal and osteoarthritis conditions. Best Pract Res Clin Rheumatol. 2008;22:351–384. doi: 10.1016/j.berh.2008.02.001. PubMed DOI
Liacini A, Sylvester J, Li WQ, Zafarullah M. Mithramycin downregulates proinflammatory cytokine-induced matrix metalloproteinase gene expression in articular chondrocytes. Arthritis Res Ther. 2005;7:R777–R783. doi: 10.1186/ar1735. PubMed DOI PMC
Akhtar N, Rasheed Z, Ramamurthy S, Anbazhagan AN, Voss FR, Haqqi TM. MicroRNA-27b regulates the expression of matrix metalloproteinase 13 in human osteoarthritis chondrocytes. Arthritis Rheum. 2010;62:1361–1371. doi: 10.1002/art.27329. PubMed DOI PMC
Li Z, Cheng J, Liu J. Baicalin Protects Human OA Chondrocytes Against IL-1beta-Induced Apoptosis and ECM Degradation by Activating Autophagy via MiR-766-3p/AIFM1 Axis. Drug Des Devel Ther. 2020;14:2645–2655. doi: 10.2147/DDDT.S255823. PubMed DOI PMC
Lopponen T, Korkko J, Lundan T, Seppanen U, Ignatius J, Kaariainen H. Childhood-onset osteoarthritis, tall stature, and sensorineural hearing loss associated with Arg75-Cys mutation in procollagen type II gene (COL2A1) Arthritis Rheum. 2004;51:925–932. doi: 10.1002/art.20817. PubMed DOI
Shukla GC, Singh J, Barik S. MicroRNAs: Processing, Maturation, Target Recognition and Regulatory Functions. Mol Cell Pharmacol. 2011;3:83–92. PubMed PMC
Takeda S, Bonnamy JP, Owen MJ, Ducy P, Karsenty G. Continuous expression of Cbfa1 in nonhypertrophic chondrocytes uncovers its ability to induce hypertrophic chondrocyte differentiation and partially rescues Cbfa1-deficient mice. Genes Dev. 2001;15:467–481. doi: 10.1101/gad.845101. PubMed DOI PMC
Ueta C, Iwamoto M, Kanatani N, Yoshida C, Liu Y, Enomoto-Iwamoto M, Ohmori T, et al. Skeletal malformations caused by overexpression of Cbfa1 or its dominant negative form in chondrocytes. J Cell Biol. 2001;153:87–100. doi: 10.1083/jcb.153.1.87. PubMed DOI PMC
Komori T. Molecular Mechanism of Runx2-Dependent Bone Development. Mol Cells. 2020;43:168–175. doi: 10.14348/molcells.2019.0244. PubMed DOI PMC
Cao J, Han X, Qi X, Jin X, Li X. miR-204-5p inhibits the occurrence and development of osteoarthritis by targeting Runx2. Int J Mol Med. 2018;42:2560–2568. doi: 10.3892/ijmm.2018.3811. PubMed DOI PMC
Li C, Li W, Pu G, Wu J, Qin F. Exosomes derived from miR-338-3p-modified adipose stem cells inhibited inflammation injury of chondrocytes via targeting RUNX2 in osteoarthritis. J Orthop Surg Res. 2022;17:567. doi: 10.1186/s13018-022-03437-2. PubMed DOI PMC