Vol 59, No 1 (2021)
Original paper
Published online: 2021-02-12

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Potential of miR-25-3p in protection of chondrocytes: emphasis on osteoarthritis

Xiao He1, Lili Deng2
Pubmed: 33576470
Folia Histochem Cytobiol 2021;59(1):30-39.

Abstract

Introduction. Osteoarthritis (OA) is the most prevailing musculoskeletal dysfunction triggered by lesions in synovial membranes and articular cartilage. MicroRNAs (miRNAs) have emerged as crucial regulators participated in many biological processes, such as osteoarthritis. This study was undertaken to address the role of miR-25-3p in the apoptosis of rat chondrocytes under an OA-like condition and its underlying mechanism.

Material and methods. OA cellular model was established in rat chondrocytes by TNF-a induction. Then, qRTPCR and Western blotting were utilized for evaluation of the expressions of miR-25-3p and insulin-like growth factor-binding protein 7 (IGFBP7), CCK-8 assay for inspection of chondrocyte viability, flow cytometry for assessment of cell apoptosis rate, Western blotting for the detection of cleaved caspase-3 level and dual-luciferase reporter gene assay for verification of the targeting relationship between miR-25-3p and IGFBP7.

Results. The miR-25-3p expression was decreased and IGFBP7 was elevated in TNF-a-induced rat chondrocytes. The miR-25-3p inhibited chondrocyte apoptosis and IGFBP7 promoted apoptosis as evidenced by enhanced cell viability and suppressed cell apoptosis in OA chondrocytes after miR-25-3p overexpression or IGFBP7 knockdown. The miR-25-3p facilitated chondrocyte viability and repressed cell apoptosis in OA by negatively regulating IGFBP7.

Conclusions. MiR-25-3p negatively regulates IGFBP7 to promote chondrocyte proliferation and restrain chondrocyte apoptosis. Our findings suggest that the regulation of IGFBP7 by miR-25-3p may emerge as a novel therapeutic regimen for OA.

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References

  1. Qiong J, Xia Z, Jing L, et al. Synovial mesenchymal stem cells effectively alleviate osteoarthritis through promoting the proliferation and differentiation of meniscus chondrocytes. Eur Rev Med Pharmacol Sci. 2020; 24(4): 1645–1655.
  2. Zou L, Liu J, Lu H. Influence of protein kinase RIPK4 expression on the apoptosis and proliferation of chondrocytes in osteoarthritis. Mol Med Rep. 2018; 17(2): 3078–3084.
  3. Charlier E, Deroyer C, Ciregia F, et al. Chondrocyte dedifferentiation and osteoarthritis (OA). Biochemical Pharmacology. 2019; 165: 49–65.
  4. Charlier E, Relic B, Deroyer C, et al. Insights on Molecular Mechanisms of Chondrocytes Death in Osteoarthritis. Int J Mol Sci. 2016; 17(12).
  5. Yang Bo, Ni J, Long H, et al. IL-1β-induced miR-34a up-regulation inhibits Cyr61 to modulate osteoarthritis chondrocyte proliferation through ADAMTS-4. J Cell Biochem. 2018; 119(10): 7959–7970.
  6. Wang X, Guo Y, Wang C, et al. MicroRNA-142-3p Inhibits Chondrocyte Apoptosis and Inflammation in Osteoarthritis by Targeting HMGB1. Inflammation. 2016; 39(5): 1718–1728.
  7. Miao G, Zang X, Hou H, et al. Bax Targeted by miR-29a Regulates Chondrocyte Apoptosis in Osteoarthritis. Biomed Res Int. 2019; 2019: 1434538.
  8. Duan ZX, Huang P, Tu C, et al. MicroRNA-15a-5p Regulates the Development of Osteoarthritis by Targeting PTHrP in Chondrocytes. Biomed Res Int. 2019; 2019: 3904923.
  9. Wu XF, Zhou ZH, Zou J. MicroRNA-181 inhibits proliferation and promotes apoptosis of chondrocytes in osteoarthritis by targeting PTEN. Biochem Cell Biol. 2017; 95(3): 437–444.
  10. Li R, Wen Y, Wu B, et al. MicroRNA-25-3p suppresses epileptiform discharges through inhibiting oxidative stress and apoptosis via targeting OXSR1 in neurons. Biochem Biophys Res Commun. 2020; 523(4): 859–866.
  11. Yao Y, Sun F, Lei M. miR-25 inhibits sepsis-induced cardiomyocyte apoptosis by targetting PTEN. Biosci Rep. 2018; 38(2).
  12. Ye C, Hou W, Chen Mo, et al. IGFBP7 acts as a negative regulator of RANKL-induced osteoclastogenesis and oestrogen deficiency-induced bone loss. Cell Prolif. 2020; 53(2): e12752.
  13. Benatar T, Yang W, Amemiya Y, et al. IGFBP7 reduces breast tumor growth by induction of senescence and apoptosis pathways. Breast Cancer Res Treat. 2012; 133(2): 563–573.
  14. Aki T, Hashimoto Ko, Ogasawara M, et al. A whole-genome transcriptome analysis of articular chondrocytes in secondary osteoarthritis of the hip. PLoS One. 2018; 13(6): e0199734.
  15. Gao ZQ, Guo X, Duan C, et al. Altered aggrecan synthesis and collagen expression profiles in chondrocytes from patients with Kashin-Beck disease and osteoarthritis. J Int Med Res. 2012; 40(4): 1325–1334.
  16. Kayal RA, Siqueira M, Alblowi J, et al. TNF-alpha mediates diabetes-enhanced chondrocyte apoptosis during fracture healing and stimulates chondrocyte apoptosis through FOXO1. J Bone Miner Res. 2010; 25(7): 1604–1615.
  17. Pearson MJ, Philp AM, Heward JA, et al. Long Intergenic Noncoding RNAs Mediate the Human Chondrocyte Inflammatory Response and Are Differentially Expressed in Osteoarthritis Cartilage. Arthritis Rheumatol. 2016; 68(4): 845–856.
  18. Li Y, Li S, Luo Y, et al. LncRNA PVT1 Regulates Chondrocyte Apoptosis in Osteoarthritis by Acting as a Sponge for miR-488-3p. DNA Cell Biol. 2017; 36(7): 571–580.
  19. Tan Li, Harper L, McNulty MA, et al. High-fat diet induces endoplasmic reticulum stress to promote chondrocyte apoptosis in mouse knee joints. FASEB J. 2020; 34(4): 5818–5826.
  20. Chen J, Wu X. MicroRNA-103 contributes to osteoarthritis development by targeting Sox6. Biomed Pharmacother. 2019; 118: 109186.
  21. Wang Xi, Ning Y, Zhou B, et al. Integrated bioinformatics analysis of the osteoarthritis‑associated microRNA expression signature. Mol Med Rep. 2018; 17(1): 1833–1838.
  22. Coutinho de Almeida R, Ramos YFM, Mahfouz A, et al. RNA sequencing data integration reveals an miRNA interactome of osteoarthritis cartilage. Ann Rheum Dis. 2019; 78(2): 270–277.
  23. Li H, Bai B, Wang J, et al. Identification of key mRNAs and microRNAs in the pathogenesis and progression of osteoarthritis using microarray analysis. Mol Med Rep. 2017; 16(4): 5659–5666.
  24. Yu C, Chen WP, Wang XH. MicroRNA in osteoarthritis. J Int Med Res. 2011; 39(1): 1–9.
  25. Kolhe R, Hunter M, Liu S, et al. Gender-specific differential expression of exosomal miRNA in synovial fluid of patients with osteoarthritis. Sci Rep. 2017; 7(1): 2029.
  26. Wang M, Yang YOu, Jin Q, et al. Function of miR-25 in the invasion and metastasis of esophageal squamous carcinoma cells and bioinformatical analysis of the miR-106b-25 cluster. Exp Ther Med. 2018; 15(1): 440–446.
  27. Rao HC, Wu ZK, Wei Sd, et al. MiR-25-3p Serves as an Oncogenic MicroRNA by Downregulating the Expression of Merlin in Osteosarcoma. Cancer Manag Res. 2020; 12: 8989–9001.
  28. Wu T, Hu H, Zhang T, et al. miR-25 Promotes Cell Proliferation, Migration, and Invasion of Non-Small-Cell Lung Cancer by Targeting the LATS2/YAP Signaling Pathway. Oxid Med Cell Longev. 2019; 2019: 9719723.
  29. Chen H, Pan H, Qian Yi, et al. MiR-25-3p promotes the proliferation of triple negative breast cancer by targeting BTG2. Mol Cancer. 2018; 17(1): 4.
  30. Chen D, Siddiq A, Emdad L, et al. Insulin-like growth factor-binding protein-7 (IGFBP7): a promising gene therapeutic for hepatocellular carcinoma (HCC). Mol Ther. 2013; 21(4): 758–766.
  31. Zhang Le, Lian R, Zhao J, et al. IGFBP7 inhibits cell proliferation by suppressing AKT activity and cell cycle progression in thyroid carcinoma. Cell Biosci. 2019; 9: 44.
  32. Verhagen HJ, de Leeuw DC, Roemer MGm, et al. IGFBP7 induces apoptosis of acute myeloid leukemia cells and synergizes with chemotherapy in suppression of leukemia cell survival. Cell Death Dis. 2014; 5: e1300.
  33. Yang Q, Zhou Y, Cai P, et al. Downregulation of microRNA-23b-3p alleviates IL-1β-induced injury in chondrogenic CHON-001 cells. Drug Des Devel Ther. 2019; 13: 2503–2512.
  34. Yu Y, Zhao J. Modulated Autophagy by MicroRNAs in Osteoarthritis Chondrocytes. Biomed Res Int. 2019; 2019: 1484152.
  35. Jeon OkH, Wilson DR, Clement CC, et al. Senescence cell-associated extracellular vesicles serve as osteoarthritis disease and therapeutic markers. JCI Insight. 2019; 4(7).