Basic Research

Effect of mangiferin on differentiation of bone marrow mesenchymal stem cells induced by homocysteine

  • Suzhen CHAO ,
  • Nian ZHOU ,
  • Xinyi SHI ,
  • Yili ZHOU ,
  • Junjie XIA ,
  • Bo LIU ,
  • Mingshi REN ,
  • Zihan. LI
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  • *.School of Medicine,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,Jiangxi,China
    *.School of Pharmacy,Nanchang Medical College,Nanchang 330052,Jiangxi,China

Received date: 2024-06-28

  Online published: 2024-12-16

Abstract

Objective To establish a lipid differentiation model of primary rat bone marrow mesenchymal stem cells (rBMSCs) in vitro using homocysteine (Hcy), and analyze the specific effects of Hcy on lipid and bone differentiation of BMSCs; to comprehensively explore the effects of mangiferin on lipid and bone differentiation of BMSCs, and further reveal the potential mechanism of mangiferin in the treatment of osteoporosis through the intervention of Hcy-induced BMSCs by different concentrations of mangiferin. Methods First, rBMSCs were extracted and isolated. The rBMSCs that were well-cultured to a certain generation were placed in culture medium containing different concentrations of Hcy (0.125, 0.250, 0.5, 1, 2, 4 mmol/L) to establish lipid differentiation model of rBMSCs. Then, different concentrations of mangiferin (37.5, 75, 150 μmol/L) were applied to the experimental cells for intervention. After culture for a certain period of time, the cells were collected for the following tests: The accumulation of lipids in the cells was detected by semi-quantitative method of oil red O dye solution to evaluate the degree of lipid differentiation; The activity of alkaline phosphatase (ALP) was measured by ρNPP method; The expression of bone morphogenetic protein-2 (BMP-2) and type I collagen (ColⅠ) were detected by western blot assay to evaluate the degree of bone differentiation. Results Mangiferin could significantly up-regulate the expression of BMP-2 and ColⅠ in vitro, increase the level of ALP, and promote bone differentiation of rBMSCs. Hcy promoted lipid differentiation of rBMSCs by increasing lipid accumulation, and down-regulated the expression of BMP-2 and ColⅠ, reduced the intracellular ALP level, thereby inhibiting bone differentiation of rBMSCs. However, the above Hcy-related effects could be successfully reversed by mangiferin. Conclusion Mangiferin can significantly promote bone differentiation of rBMSCs in vitro, while Hcy can inhibit bone differentiation of rBMSCs and promote its lipid differentiation. Mangiferin has the ability to reverse this effect, indicating that mangiferin has certain potential in the treatment of osteoporosis-related diseases.

Cite this article

Suzhen CHAO , Nian ZHOU , Xinyi SHI , Yili ZHOU , Junjie XIA , Bo LIU , Mingshi REN , Zihan. LI . Effect of mangiferin on differentiation of bone marrow mesenchymal stem cells induced by homocysteine[J]. The Journal of Practical Medicine, 2024 , 40(23) : 3284 -3290 . DOI: 10.3969/j.issn.1006-5725.2024.23.002

References

1 付银锋, 史栋梁, 马永胜, 等. 骨质疏松症外周血miR-141评价骨折风险的价值[J], 实用医学杂志, 2023, 39(4): 447-450. doi:10.3969/j.issn.1006-5725.2023.04.010
2 陈颖, 何柳柳, 邓伟民, 等. 唑来膦酸治疗原发性骨质疏松症的长期疗效[J], 实用医学杂志, 2023, 39(10): 1278-1284. doi:10.3969/j.issn.1006-5725.2023.10.016
3 LIU J, GAO J, LIANG Z, et al. Mesenchymal stem cells and their microenvironment[J]. Stem Cell Res Ther, 2022, 13(1):429. doi:10.1186/s13287-022-02985-y
4 YU H, LIU P, ZHU D, et al. Chrysophanic acid shifts the differentiation tendency of BMSCs to prevent alcohol-induced osteonecrosis of the femoral head[J]. Cell Prolif, 2020, 53(8):e12871. doi:10.1111/cpr.12871
5 陈斌伟, 刘圣曜, 黄帅, 等. 辛伐他汀联合机械牵拉激活Wnt/β-catenin信号通路促进大鼠骨髓间充质干细胞成骨分化[J], 实用医学杂志, 2021, 37(1) : 41-45.
6 JIANG Y, ZHANG P, ZHANG X, et al. Advances in mesenchymal stem cell transplantation for the treatment of osteoporosis[J]. Cell Prolif, 2021, 54(1):e12956. doi:10.1111/cpr.12956
7 HERMANN A, SITDIKOVA G. Homocysteine: Biochemistry, Molecular Biology and Role in Disease[J]. Biomolecules, 2021, 11(5):737. doi:10.3390/biom11050737
8 ZHU Z, LIU C, LI X, et al. Association between plasma total homocysteine level within normal range and bone mineral density in adults[J]. J Orthop Surg Res, 2020, 15(1):475. doi:10.1186/s13018-020-02012-x
9 ILESANMI-OYELERE B L, KRUGER M C. B vitamins and homocysteine as determinants of bone health: A literature review of human studies[J]. J Hum Nutr Diet,2023, 36(3):1031-1044. doi:10.1111/jhn.13080
10 ZHAO J, LU Q, ZHANG X. Associations of serum vitamin B12 and its biomarkers with musculoskeletal health in middle-aged and older adults[J]. Front Endocrinol (Lausanne), 2024, 15:1387035. doi:10.3389/fendo.2024.1387035
11 ZIVKOVI? J, KUMAR K A, RUSHENDRAN R, et al. Pharmacological properties of mangiferin: bioavailability, mechanisms of action and clinical perspectives[J]. Naunyn Schmiedebergs Arch Pharmacol, 2024, 397(2):763-781. doi:10.1007/s00210-023-02682-4
12 HE J, WANG X, ZHAO D, et al. Mangiferin promotes osteogenic differentiation and alleviates osteoporosis in the ovariectomized mouse via the AXL/ERK5 pathway[J]. Front Pharmacol, 2022, 13:1028932. doi:10.3389/fphar.2022.1028932
13 SWAIN S, KODURU J R, RAUTRAY T R. Mangiferin-Enriched Mn-Hydroxyapatite Coupled with β-TCP Scaffolds Simultaneously Exhibit Osteogenicity and Anti-Bacterial Efficacy[J]. Materials (Basel), 2023, 16(6):2206. doi:10.3390/ma16062206
14 GU Y, HU Y, HUANG S, et al. CpG ODN/Mangiferin Dual Delivery through Calcium Alginate Hydrogels Inhibits Immune-Mediated Osteoclastogenesis and Promotes Alveolar Bone Regeneration in Mice[J]. Biology (Basel), 2023, 12(7):976. doi:10.3390/biology12070976
15 BAI Y, LIU C, FU L, et al. Mangiferin enhances endochondral ossification-based bone repair in massive bone defect by inducing autophagy through activating AMP-activated protein kinase signaling pathway[J]. FASEB J, 2018, 32(8):4573-4584. doi:10.1096/fj.201701411r
16 王雪,杨娟,袁红,等. 丹参素冰片酯对同型半胱氨酸诱导大鼠骨髓间充质干细胞损伤的保护作用及机制 [J]. 中华心血管病杂志, 2017, 45(2):130-136.
17 李小琴, 汪乐新, 马小军, 等. 高同型半胱氨酸经TRPC6/NF-κB诱导肾小球足细胞铁死亡的机制 [J]. 实用医学杂志, 2024,40(2):174-181.
18 YUAN D, CHU J, LIN H, et al. Mechanism of homocysteine-mediated endothelial injury and its consequences for atherosclerosis[J]. Front Cardiovasc Med, 2023, 9:1109445. doi:10.3389/fcvm.2022.1109445
19 WANG C, ZHANG X, QIU B. Genetically predicted circulating serum homocysteine levels on osteoporosis: a two-sample mendelian randomization study[J]. Sci Rep, 2023, 13(1):9063. doi:10.1038/s41598-023-35472-2
20 DE MARTINIS M, SIRUFO M M, NOCELLI C, et al. Hyperhomocysteinemia is Associated with Inflammation, Bone Resorption, Vitamin B12 and Folate Deficiency and MTHFR C677T Polymorphism in Postmenopausal Women with Decreased Bone Mineral Density[J]. Int J Environ Res Public Health, 2020, 17(12):4260. doi:10.3390/ijerph17124260
21 ANAGNOSTIS P, FLORENTIN M, LIVADAS S, et al. Bone Health in Patients with Dyslipidemias: An Underestimated Aspect[J]. Int J Mol Sci, 2022, 23(3):1639. doi:10.3390/ijms23031639
22 ALKAISSI H, MCFARLANE S I. Hyperhomocysteinemia and Accelerated Aging: The Pathogenic Role of Increased Homocysteine in Atherosclerosis, Osteoporosis, and Neurodegeneration[J]. Cureus, 2023, 15(7):e42259.
23 SELVARAJ V, SEKARAN S, DHANASEKARAN A, et al. Type 1 collagen: Synthesis, structure and key functions in bone mineralization[J]. Differentiation, 2024, 136:100757. doi:10.1016/j.diff.2024.100757
24 WANG L, NIU H, ZHANG J. Homocysteine induces mitochondrial dysfunction and oxidative stress in myocardial ischemia/reperfusion injury through stimulating ROS production and the ERK1/2 signaling pathway[J]. Exp Ther Med, 2020, 20(2):938-944. doi:10.3892/etm.2020.8735
25 CHU D T, PHUONG T N T, TIEN N L B, et al. An Update on the Progress of Isolation, Culture, Storage, and Clinical Application of Human Bone Marrow Mesenchymal Stem/Stromal Cells[J]. Int J Mol Sci, 2020, 21(3):708. doi:10.3390/ijms21030708
26 DUTTA T, DAS T, GOPALAKRISHNAN A V, et al. Mangiferin: the miraculous xanthone with diverse pharmacological properties[J]. Naunyn Schmiedebergs Arch Pharmacol, 2023, 396(5):851-863. doi:10.1007/s00210-022-02373-6
27 DENG X, LIN B, WANG F, et al. Mangiferin attenuates osteoporosis by inhibiting osteoblastic ferroptosis through Keap1/Nrf2/SLC7A11/GPX4 pathway[J]. Phytomedicine, 2024, 124:155282. doi:10.1016/j.phymed.2023.155282
28 GU Y, ZHANG L, BAI Y. Mangiferin promotes the osteogenic differentiation of human periodontal ligament stem cells via TGF?β/SMAD2 signaling[J]. Mol Med Rep, 2022, 26(2):266. doi:10.3892/mmr.2022.12782
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