网络出版日期: 2021-08-03
基金资助
国家自然科学基金青年基金(81800979)
Effect of miR-877-3p on proliferation of bone marrow mesenchymal stem cells in osteoporosis
Online published: 2021-08-03
Supported by
National Natural Science Foundation of China for Young Scholars(81800979)
目的·研究骨质疏松症发生及发展过程中miR-877-3p对骨髓间充质干细胞(bone mesenchymal stem cells,BMSCs)增殖能力的影响。方法·8周龄的雌性健康小鼠20只,进行双侧卵巢摘除术,建立绝经后骨质疏松模型(OVX组)。另选20只雌性健康小鼠,切除卵巢附近脂肪组织,建立假手术模型(假手术组)。术后2个月,对2组小鼠骨参数指标包括骨体积分数、骨小梁数量及骨密度行micro-CT检测;采用CCK-8法和细胞计数法检测2组BMSCs增殖能力;通过实时荧光PCR(real-time PCR)检测2组细胞miR-877-3p的表达。上调(下调)细胞内miR-877-3p水平,通过CCK-8法和细胞计数法检测BMSCs增殖能力的变化。结果·Micro-CT检测结果显示,假手术组与OVX组各项骨参数指标比较,差异均有统计学意义(P<0.05)。CCK-8法及细胞计数结果显示,假手术组BMSCs的增殖能力明显高于OVX组(P<0.05)。Real-time PCR结果显示,假手术组BMSCs中miR-877-3p的表达明显低于OVX组(P<0.05)。上调(下调)miR-877-3p后,BMSCs增殖能力下降(上升)。结论·绝经后骨质疏松症小鼠中,BMSCs的增殖能力受到miR-877-3p调控,这可能是影响骨质疏松发病的重要因素之一。
关键词: 骨髓间充质干细胞; 增殖; miR-877-3p; 绝经
童徐 , 舒林径 . miR-877-3p对骨质疏松症小鼠骨髓间充质干细胞增殖能力的影响[J]. 上海交通大学学报(医学版), 2021 , 41(7) : 884 -890 . DOI: 10.3969/j.issn.1674-8115.2021.07.006
·To investigate the effect of miR-877-3p on the proliferation of bone marrow mesenchymal stem cells (BMSCs) during the occurrence and development of osteoporosis.
·Twenty female healthy mice aged 8 weeks underwent bilateral ovariectomy to establish the postmenopausal osteoporosis models (OVX group). In addition, 20 healthy female mice were selected in the same period and the adipose tissue near the ovary was removed to establish sham operation models (Sham group). Two months after surgery, bone parameters of the mice, including bone volume fraction (BVF), trabecular number (Tb.N), and bone mineral density (BMD) were detected by micro-CT, and cell proliferation ability of the two groups was detected by CCK-8 and cell counting. The expression of miR-877-3p in the two groups was detected by real-time PCR. After up-regulating (down-regulating) the level of miR-877-3p in the BMSCs, cell proliferation was detected by CCK-8 and cell counting.
·The micro-CT results showed that there were significant differences in bone parameters between the Sham group and the OVX group (P<0.05). The results of CCK-8 and cell counting showed that the proliferation ability of BMSCs in the Sham group was significantly higher than that in the OVX group (P<0.05). Real-time PCR results showed that the expression of miR-877-3p in BMSCs in the Sham group was significantly lower than that in the OVX group (P<0.05). After upregulation (downregulation) of miR-877-3p, the proliferation ability of BMSCs decreased (increased).
·In postmenopausal osteoporosis mice, the proliferation ability of BMSCs is regulated by miR-877-3p, which may be one of the important factors affecting the incidence of osteoporosis.
Key words: bone mesenchymal stem cells; proliferation; miR-877-3p; menopause
1 | Pavel OR, Popescu M, Novac L, et al. Postmenopausal osteoporosis: clinical, biological and histopathological aspects[J]. Romanian J Morphol Embryol, 2016, 57(1): 121-130. |
2 | Moskaleva EY, Semochkina YP, Shuvatova VG, et al. Mesenchymal stem cells from mouse adipose tissue stimulate tumor growth[J]. Bull Exp Biol Med, 2019, 167(1): 145-149. |
3 | Shuai Y, Yang R, Mu R, et al. MiR-199a-3p mediates the adipogenic differentiation of bone marrow-derived mesenchymal stem cells by regulating KDM6A/WNT signaling[J]. Life Sci, 2019, 220: 84-91. |
4 | Mortada I, Mortada R. Epigenetic changes in mesenchymal stem cells differentiation[J]. Eur J Med Genet, 2018, 61(2): 114-118. |
5 | Zheng XD, Yu Y, Shao BY, et al. Osthole improves therapy for osteoporosis through increasing autophagy of mesenchymal stem cells[J]. Exp Anim, 2019, 68(4): 453-463. |
6 | Shao BY, Liao L, Yu Y, et al. Estrogen preserves Fas ligand levels by inhibiting microRNA-181a in bone marrow-derived mesenchymal stem cells to maintain bone remodeling balance[J]. FASEB J, 2015, 29(9): 3935-3944. |
7 | Yu Y, Liao L, Shao BY, et al. Knockdown of microRNA Let-7a improves the functionality of bone marrow-derived mesenchymal stem cells in immunotherapy[J]. Mol Ther, 2017, 25(2): 480-493. |
8 | Kozomara A, Birgaoanu M, Griffiths-Jones S. miRBase: from microRNA sequences to function[J]. Nucleic Acids Res, 2019, 47(d1): D155-D162. |
9 | Ritchie W. microRNA target prediction[J]. Methods Mol Biol Clifton N J, 2017, 1513: 193-200. |
10 | Wang C, Gu S, Cao H, et al. miR-877-3p targets Smad7 and is associated with myofibroblast differentiation and bleomycin-induced lung fibrosis[J]. Sci Rep, 2016, 6: 30122. |
11 | Zablotni A, Dakischew O, Trinkaus K, et al. Regulation of acetylcholine receptors during differentiation of bone mesenchymal stem cells harvested from human reaming debris[J]. Int Immunopharmacol, 2015, 29(1): 119-126. |
12 | Li Y, Feng C, Gao M, et al. MicroRNA-92b-5p modulates melatonin-mediated osteogenic differentiation of bone marrow mesenchymal stem cells by targeting ICAM-1[J]. J Cell Mol Med, 2019, 23(9): 6140-6153. |
13 | Chen R, Qiu H, Tong Y, et al. MiRNA-19a-3p alleviates the progression of osteoporosis by targeting HDAC4 to promote the osteogenic differentiation of hMSCs[J]. Biochem Biophys Res Commun, 2019, 516(3): 666-672. |
14 | Shuai Y, Liao L, Su X, et al. Melatonin treatment improves mesenchymal stem cells therapy by preserving stemness during long-term in vitro expansion[J]. Theranostics, 2016, 6(11): 1899-1917. |
15 | Tan FZ, Dai HL. TAZ accelerates osteogenesis differentiation of mesenchymal stem cells via targeting PI3K/Akt [J]. Eur Rev Med Pharmacol Sci, 2019, 23(3): 81-88. |
16 | Qi M, Zhang L, Ma Y, et al. Autophagy maintains the function of bone marrow mesenchymal stem cells to prevent estrogen deficiency-induced osteoporosis[J]. Theranostics, 2017, 7(18): 4498-4516. |
17 | Wang L, Chen K, Wan X, et al. NLRP3 inflammasome activation in mesenchymal stem cells inhibits osteogenic differentiation and enhances adipogenic differentiation[J]. Biochem Biophys Res Commun, 2017, 484(4): 871-877. |
18 | Xie Y, Chen Y, Zhang L, et al. The roles of bone-derived exosomes and exosomal microRNAs in regulating bone remodelling[J]. J Cell Mol Med, 2017, 21(5): 1033-1041. |
19 | He G, Chen J, Huang D. miR-877-3p promotes TGF-β1-induced osteoblast differentiation of MC3T3-E1 cells by targeting Smad7[J]. Exp Ther Med, 2019, 18(1): 312-319. |
20 | Li S, Zhu Y, Liang Z, et al. Up-regulation of p16 by miR-877-3p inhibits proliferation of bladder cancer[J]. Oncotarget, 2016, 7(32): 51773-51783. |
21 | Xu X, Zheng S. MiR-887-3p negatively regulates STARD13 and promotes pancreatic cancer progression[J]. Cancer Manag Res, 2020, 12: 6137-6147. |
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