Mulberry aqueous extract regulates rno-miR-139/MMP14 to promote chondrogenic differentiation of bone marrow mesenchymal stem cells

doi:10.13418/j.issn.1001-165x.2025.3.10

PDF(5258 KB)

Chinese Journal of Clinical Anatomy ›› 2025, Vol. 43 ›› Issue (3) : 305-312. DOI: 10.13418/j.issn.1001-165x.2025.3.10

Mulberry aqueous extract regulates rno-miR-139/MMP14 to promote chondrogenic differentiation of bone marrow mesenchymal stem cells

Ye Haoxiang, Liu Zike, Ye Baolin, Liu Aijun*

Author information +

History +

Abstract

Objective To investigate the mechanism of mulberry aqueous extract promoting chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSC). Methods BMSCs were extracted by the whole bone marrow adherent method. The CCK8 assay was used to detect the proliferation of BMSCs induced by mulberry aqueous extract on cells. RT-qPCR was used to test miRNAs in BMSCs treated by mulberry aqueous extract. Biological information prediction and the dual luciferase reporter gene validated that MMP14 was regulated by rno-miR-139. RT-qPCR and WB were used to detect the effect of rno-miR-139 mimic and inhibitor on MMP14 expression. siMMP14 transfected BMSCs to detect the expression of Sox9. Immunohistochemistry was used to detect rno-miR-139 regulate chondrogenic differentiation of BMSCs in ectopic transplantation in vivo. Results The mulberry aqueous extract effectively promoted the chondrogenic differentiation of BMSCs. The downregulation of rno-miR-139 targeted the upregulation of MMP14 and promoted the expression of Sox9. The downregulated rno-miR-139 lead to upregulating Sox9 and Collagen II in ectopic cartilage differentiation of BMSCs in vivo. Conclusions Mulberry aqueous extract inhibits rno-miR-139 by upregulating MMP14 to promote chondrogenic differentiation of BMSCs.

Key words

Mulberry aqueous extrac; / / rno-miR-139; / MMP14; / Bone marrow mesenchymal stem cells; / / Chondrogenic differentiation

Cite this article

EndNote

Ris (Procite)

Bibtex

Download Citations

Ye Haoxiang, Liu Zike, Ye Baolin, Liu Aijun. Mulberry aqueous extract regulates rno-miR-139/MMP14 to promote chondrogenic differentiation of bone marrow mesenchymal stem cells[J]. Chinese Journal of Clinical Anatomy. 2025, 43(3): 305-312 https://doi.org/10.13418/j.issn.1001-165x.2025.3.10

References

[1] Gonzalez-Fernandez P, Rodríguez-Nogales C, Jordan O, et al. Combination of mesenchymal stem cells and bioactive molecules in hydrogels for osteoarthritis treatment[J]. Eur J Pharm Biopharm, 2022, 172:41-52. DOI: 10.1016/j.ejpb.2022.01.003.
[2] 殷海波, 王海南, 刘宏潇, 等. 从肾藏象论衰老与骨关节炎[J]. 中医杂志, 2012, 53(14): 1192-1194. DOI :10.13288/j.11-2166/r.2012.14.007.
Yin HB, Wang HN, Liu HX, et al. On aging and osteoarthritis from the perspective of the kidney theory in TCM visceral manifestation doctrine [J]. Journal of Traditional Chinese Medicine, 2012, 53(14):1192-1194. DOI: 10.13288/j.11-2166/r.2012.14.007.
[3] 郑冬阳, 于静, 金明秀. 基于肾藏精主骨生髓论治骨关节炎[J]. 光明中医,2023, 38(22): 4347-4349. DOI:10.3969/j.issn.1003-8914. 2023. 22.011.
Zheng DY, Yu J, Jin MX. Treatment of osteoarthritis based on the theory of the kidney contains the essence to dominate the bone and produce the marrow[J]. Guangming Journal of Chinese Medicine, 2023, 38(22): 4347-4349. DOI:10.3969/j.issn.1003-8914.2023.22.011.
[4] Diener C, Keller A, Meese E. Emerging concepts of miRNA therapeutics: from cells to clinic[J]. Trends Genet, 2022, 38(6): 613-626. DOI: 10.1016/j.tig.2022.02.006.
[5] Xu H, Ding C, Guo C, et al . Suppression of CRLF1 promotes the chondrogenic differentiation of bone marrow-derived mesenchymal stem and protects cartilage tissue from damage in osteoarthritis via activation of miR-320[J]. Mol Med, 2021, 27(1): 116. DOI: 10.1186/s10020-021-00369-1.
[6] 陈祁青, 金红婷, 应俊, 等. 右归饮含药血清对骨髓间充质干细胞成软骨分化的促进作用及其microRNA表达谱分析[J]. 中华中医药杂志, 2015, 30(5): 1380-1386. DOI: CNKI:SUN:BXYY.0.2015-05-004.

Chen QQ, Jin HT, Ying J, et al. Promoting effect of Youguiyin medicated serum in chondrogenesis differentiation of bone expression profile of microRNA[J]. China Journal of Traditional Chinese Medicine and Pharmacy, 2015, 30(5): 1380-1386. DOI: CNKI:SUN:BXYY.0.2015-05-004.

[7] 靳俊峰, 刘银花, 欧小波, 等. 桑葚水提物抑制H2O2诱导BMSCs成脂分化的研究[J]. 安徽医科大学学报, 2020, 55(7): 1098-1102. DOI :10.19405/j.cnki.issn1000-1492.2020.07.022.
Jin JF, Liu YH, Ou XB, et al. The aqueous extracts of mulberry inhibited adipogenic differentiation of BMSCs induced by H2O2[J]. Acta Universitatis Medicinalis Anhui, 2020, 55(7): 1098-1102. DOI :10.19405/j.cnki.issn1000-1492.2020.07.022.
[8] 黄炜平, 李可, 刘爱军, 等. 芥子碱对H2O2诱导BMSCs成脂分化的影响[J]. 中国病理生理杂志, 2018, 34(5): 918-924. DOI: 10.3969/j.issn.1000-4718.2018.05.023.
Huang WP, Li K, Liu AJ, et al. Effect of sinapine on H2O2-induced adipogenic differentiation of bone marrow mesenchymal stem cells[J]. Chinese Journal of Pathophysiology, 2018, 34(5): 918-924. DOI: 10.3969/j.issn.1000-4718.2018.05.023.
[9] Fujii Y, Liu L, Yagasaki L, et al . Cartilage homeostasis and osteoarthritis[J]. Int J Mol Sci, 2022, 23(11):6316. DOI: 10.3390/ijms23116316.
[10]周勇, 郑树灿, 邵海宾, 等. 基于TGFβ1/Smad信号通路在骨髓间充质干细胞修复骨质疏松大鼠牙槽骨缺损的机制研究[J]. 临床口腔医学杂志, 2023, 39(11):643-648. DOI: 10.3969/j.issn.1003-1634. 2023. 11. 002.
Zhou Y, Zheng SC, Shao HB, et al. Discussion on the mechanism of bone marrow mesenchymal stem cells in repairing alveolar bone defects in osteoporotic rats based on TGFβ1/Smad signaling pathway[J]. Journal of Clinical Stomatology, 2023, 39(11): 643-648. DOI: 10.3969/j.issn.1003-1634.2023.11.002.
[11]Strouhalova K, Tolde O, Rosel D, et al . Cytoplasmic tail of MT1-MMP: a hub of MT1-MMP regulation and function[J]. Int J Mol Sci, 2023, 24(6): 5068. DOI: 10.3390/ijms24065068.
[12]Mhanna R, Öztürk E, Vallmajo-Martin Q, et al . GFOGER-modified MMP-sensitive polyethylene glycol hydrogels induce chondrogenic differentiation of human mesenchymal stem cells[J]. Tissue Eng Part A, 2014, 20(7-8):1165-1174. DOI: 10.1089/ten.TEA.2013.0519.
[13]Zhang HX, Sun C, Yu HC, et al . Targeted inhibition of β-catenin by miR-320 and decreased MMP-13 expression in suppressing chondrocyte collagen degradation[J]. Eur Rev Med Pharmacol Sci, 2018, 22(18):5828-5835. DOI: 10.26355/eurrev_201809_15909.
[14]Sioud M. RNA interference: story and mechanisms[J]. Methods Mol Biol, 2021, 2282:1-15. DOI: 10.1007/978-1-0716-1298-9_1.
鈥�