骨髓间充质干细胞成脂成骨平衡调控研究进展

占秀文 杨磊 郑美蓉 汪鑫平 许晓源

解剖学报 ›› 2019, Vol. 50 ›› Issue (3) : 400-404.

PDF(997 KB)
欢迎访问《解剖学报》官方网站!今天是 English
PDF(997 KB)
解剖学报 ›› 2019, Vol. 50 ›› Issue (3) : 400-404. DOI: 10.16098/j.issn.0529-1356.2019.03.023
综述

骨髓间充质干细胞成脂成骨平衡调控研究进展

  • 占秀文1 杨磊1,2* 郑美蓉1 汪鑫平1 许晓源1*
作者信息 +

Research progress on the balance regulation of osteogenic differentiation and adipogenic differentiation in bone marrow mesenchymal stem cell

  • ZHAN Xiu-wen1 YANG Lei 1,2* ZHENG Mei-rong1 WANG Xin-ping1 XU Xiao-yuan 1*
Author information +
文章历史 +

摘要

骨质疏松症(OP)是一种全身性的骨代谢疾病,主要表现为骨量减少、骨质脆性增加、骨骼微结构退化。随着对骨质疏松症发病机制的深入研究,骨髓间充质干细胞(BMSCs)分化失衡(成骨分化减少,成脂分化增多)是引发骨质疏松症的关键。我们总结了BMSCs成脂成骨分化相关的信号通路,充分理解这些信号通路,有利于更好的阐明骨质疏松症的发病机制,为临床医生有效地治疗骨质疏松症提供帮助。

Abstract

Osteoporosis (OP), a systemic bone metabolism disease, mainly manifested in the decrease of bone mass, the increase of bone fragility and the microstructure degeneration of the bone. Along with the in-depth research of the pathogenesis of osteoporosis, the imbalance differentiation of bone marrow mesenchymal stem cell (BMSCs) (Osteogenic differentiation decrease and adipogenic differentiation increase) is the main reason that causes osteoporosis. In this paper, we summarize the signal pathways of osteogenic differentiation and adipogenic differentiation of BMSCs. Better understand these signal pathways is conducive to elucidate and treat osteoporosis.

关键词

平衡调控 / 骨髓间充质干细胞 / 成骨分化 / 成脂分化 / 信号通路

Key words

Balance regulation / Bone marrow mesenchymal stem cell / Osteogenic differentiation / Adipogenic differentiation / Signal pathway

引用本文

导出引用
占秀文 杨磊 郑美蓉 汪鑫平 许晓源. 骨髓间充质干细胞成脂成骨平衡调控研究进展[J]. 解剖学报. 2019, 50(3): 400-404 https://doi.org/10.16098/j.issn.0529-1356.2019.03.023
ZHAN Xiu-wen YANG Lei ZHENG Mei-rong WANG Xin-ping XU Xiao-yuan. Research progress on the balance regulation of osteogenic differentiation and adipogenic differentiation in bone marrow mesenchymal stem cell[J]. Acta Anatomica Sinica. 2019, 50(3): 400-404 https://doi.org/10.16098/j.issn.0529-1356.2019.03.023

参考文献

[1] Nakajima K, Kunimatsu R, Ando K, et al. Comparison of the bone regeneration ability between stem cells from human exfoliated deciduous teeth, human dental pulp stem cells and human bone marrow mesenchymal stem cells [J]. Biochem Bioph Res Co, 2018, 497 (3): 876-882.
[2] Bagheri L, Pellati A, Rizzo P, et al. Notch pathway is active during osteogenic differentiation of human bone marrow mesenchymal stem cells induced by pulsed electromagnetic fields [J]. J Tissue Eng Regen M, 2018, 12 (2): 304-315.
[3] Yuan Z, Li Q, Luo S, et al. PPARγ and Wnt signaling in adipogenic and osteogenic differentiation of mesenchymal stem cells [J]. Curr Stem Cell Res Ther,2016,11(3):216-225
[4] Bateman ME, Strong AL, McLachlan JA, et al. The effects of endocrine disruptors on adipogenesis and osteogenesis in mesenchymal stem cells: a review [J]. Front Endocrinol, 2017,7: 171.
[5] Francisco J,Lin YM. Nitrolinoleic acid: an endogenous peroxisome proliferator-activated receptor γ ligand [J]. Proc Natl Acad Sci USA,2005, 102 (7):2340-2345. 
[6] Liao L, Su X, Yang X, et al. TNF-α inhibits Foxo1 by upregulating miR-705 to aggravate oxidative damage in bone marrow-derived mesenchymal stem cells during osteoporosis[J]. Stem Cells, 2016, 34 (4): 1054-1067.
[7] Nakashima K, De CB. Transcriptional mechanisms in osteoblast differentiation and bone formation [J]. Trends Genet, 2003, 19 (8):458-466.
[8] Wang CL, Xiao F, Wang CD, et al. Gremlin2 suppression increases the BMP 2-induced osteogenesis of human bone marrow-derived mesenchymal stem cells via the BMP2/Smad/Runx2 signaling pathway[J]. J Biol Chem, 2017, 118 (2): 286-297.
[9] Krishnan Ⅴ, Bryant HU, Macdougald OA. Regulation of bone mass by Wnt signaling [J]. J Clin Invest, 2006, 116 (5):1202-1209.
[10] Ying J, Wang P, Zhang S, et al. Transforming growth factor-beta1 promotes articular cartilage repair through canonical Smad and Hippo pathways in bone mesenchymal stem cells[J]. Life Sci, 2018, 192 (2): 84-90.
[11] Hata K, Nishimura R, Lkeda F, et al. Differential roles of Smad1 and p38 kinase in regulation of peroxisome proliferator-activating receptor gamma during bone morphogenetic protein 2-induced adipogenesis [J]. Mol Biol Cell, 2003, 14 (2):545-555.
[12] Abdallah BM. Marrow adipocytes inhibit the differentiation of mesenchymal stem cells into osteoblasts via suppressing BMP-signaling [J]. J Biomed Sci, 2017, 24 (1): 11-17.
[13] Bowers RR, Kim JW, Otto TC, et al. Stable stem cell commitment to the adipocyte lineage by inhibition of DNA methylation: role of the BMP-4 gene [J]. Proc Natl Acad Sci USA, 2006, 103 (35):13022-13027.
[14] Kang Q, Song WX, Luo Q, et al. A comprehensive analysis of the dual roles of BMPs in regulating adipogenic and osteogenic differentiation of mesenchymal progenitor cells [J]. Stem Cells Dev, 2009, 18 (4):545-559.
[15] Barati D, Shariati SRP, Moeinzadeh S, et al. Spatiotemporal release of BMP-2 and VEGF enhances osteogenic and vasculogenic differentiation of human mesenchymal stem cells and endothelial colony-forming cells co-encapsulated in a patterned hydrogel[J]. J Control Release, 2016, 223: 126-136. 
[16] Livingstone C. Insulin-like growth factor-Ⅰ (IGF-Ⅰ) and clinical nutrition [J]. Clin Sci, 2013, 125 (5):265-280. 
[17] Tang X, Chen F, Lin Q, et al. Bone marrow mesenchymal stem cells repair the hippocampal neurons and increase the expression of IGF1 after cardiac arrest in rats [J]. Exp Ther Med, 2017, 14 (5): 4312-4320.
[18] Yang SJ, Chen CY, Chang GD, et al. Activation of Akt by advanced glycation end products (AGEs): involvement of IGF-1 receptor and caveolin-1 [J]. PLoS One, 2013, 8 (3): e58100.
[19] Peng X, Xu PZ, Chen ML, et al. Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2 [J]. Gene Dev, 2003, 17 (11):1352-1365.
[20] Mccarty RC, Gronthos S, Zannettino AC, et al. Characterisation and developmental potential of ovine bone marrow derived mesenchymal stem cells [J]. J Cell Physiol, 2010, 219 (2):324-333.
[21] Chen J, Yuan K, Mao X, et al. Serum response factor regulates bone formation via IGF-1 and Runx2 signals [J]. J Bone Miner Res, 2012, 27 (8):1659-1668.-
[22] Gaur T, Lengner CJ, Hovhannisyan H, et al. Canonical WNT signaling promotes osteogenesis by directly stimulating Runx2 gene expression[J]. J Biol Chem,2005, 280 (39):33132-33140.
[23] Tao K, Xiao D, Weng J, et al. Berberine promotes bone marrow-derived mesenchymal stem cells osteogenic differentiation via canonical Wnt/β-catenin signaling pathway[J]. Toxicol Lett, 2016, 240 (1): 68-80.
[24] Gregory CA, Gunn WG, Reyes E, et al. How Wnt signaling affects bone repair by mesenchymal stem cells from the bone marrow [J]. Ann Ny Acad Sci, 2010, 1049 (1):97-106.
[25] Oshima T, Abe M, Asano J, et al. Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2 [J]. Blood, 2005, 106 (9):3160-3165.
[26] Li T, Li H, Wang Y, et al. microRNA-23a inhibits osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting LRP5 [J]. Int J Biochem Cell B, 2016, 72 (5): 55-62. 
[27] Fontaine C, Cousin W, Plaisant M, et al. Hedgehog signaling alters adipocyte maturation of human mesenchymal stem cells [J]. Stem Cells, 2010, 26 (4):1037-1046.
[28] Sinha S, Chen JK. Purmorphamine activates the Hedgehog pathway by targeting smoothened [J]. Nat Chem Biol, 2006, 2 (1):29-30.
[29] Almalki SG, Agrawal DK. Key transcription factors in the differentiation of mesenchymal stem cells[J]. Differentiation, 2016, 92 (1-2): 41-51.
[30] Aghaloo T, Cowan CM, Chou YF, et al. Nell-1-induced bone regeneration in calvarial defects [J]. Am J Pathol, 2006, 169 (3):903-915.
[31] Steven S, Lu XL, Zhang CS, et al. The osteoinductive properties of Nell-1 in a rat spinal fusion model [J].Spine J, 2007, 7 (1):50-60.
[32] Shen J, James AW, Zhang X, et al. Novel Wnt regulator NEL-like molecule-1 antagonizes adipogenesis and augments osteogenesis induced by bone morphogenetic protein 2[J]. Am J Pathol, 2016, 186 (2): 419-434. 
[33] Kwak J, Zara JN, Chiang M, et al. NELL-1 injection maintains long-bone quantity and quality in an ovariectomy-induced osteoporotic senile rat model [J]. Tissue Eng Part A, 2013, 19 (3-4):426-436.
[34] Guo Sh, Liao HY, Liu J, et al. Effects of resveratrol on Shh signaling pathway of NIH3T3 cells[J]. Acta Anatomica Sinica, 2018, 49 (2): 179-184. (in Chinese)
郭霜, 廖鸿雁, 刘杰,等. 白藜芦醇对NIH3T3细胞Shh信号通路的影响 [J]. 解剖学报, 2018, 49 (2): 179-184. 
[35] Shakibaei M, Shayan P, Busch F, et al. Resveratrol mediated modulation of Sirt-1/Runx2 promotes osteogenic differentiation of mesenchymal stem cells: potential role of Runx2 deacetylation [J]. PLoS One, 2012, 7 (4): e35712.
[36] Wang YJ, Zhao P, Sui BD, et al. Resveratrol enhances the functionality and improves the regeneration of mesenchymal stem cell aggregates[J]. Exp Mol Med, 2018, 50 (6): 74-80.
[37] Mathieu J, Ruohola BH. Regulation of stem cell populations by microRNAs[J]. Adv Exp Med Biol, 2013,12 (8):329-351.
[38] Li X, Yang Y, Yan R, et al. miR-377-3p regulates adipogenic differentiation of human bone marrow mesenchymal stem cells by regulating LIFR [J]. Mol Cell Biochem, 2018, 70 (2):1-9.
[39] Yu Z, Li Y, Fan H, et al. miRNAs regulate stem cell self-renewal and differentiation [J]. Front Genet, 2012, 12(3):191-198.
[40] Hamam D, Ali D. microRNAs as regulators of adipogenic differentiation of mesenchymal stem cells [J]. Stem Cells Dev,2015,24 (4):417-425.
[41] Zhang JF, Fu W, He ML, et al. MiR-637 maintains the balance between adipocytes and osteoblasts by directly targeting Osterix [J]. Mol Biol Cell, 2011,22 (21):3955-3961.
[42] Rahman M, Akhtar N, Jamil HM, et al. TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation [J]. Bone Res, 2015, 3(1):11-30.
[43] Hao C, Yang S, Xu W, et al. MiR-708 promotes steroid-induced osteonecrosis of femoral head, suppresses osteogenic differentiation by targeting SMAD3 [J]. Sci Rep, 2016,49(6):22599.
[44] Liu ZY, LI Q, Chen LJ, et al. Inhibition of adipogenic differentiation of bone marrow mesenchymal stem cells by all-trans retinoic acid through direct regulation of PPARγ2 by RAR [J]. Journal of Shanghai Jiaotong University (Medical Science), 2015, 35 (5): 682-687. (in Chinese)
刘祖银,李清,陈丽君,等.全反式视黄酸通过RARγ蛋白直接调控PPARγ2蛋白抑制骨髓间充质干细胞成脂分化 [J].上海交通大学学报(医学版),2015,35(5):682-687. 
[45] Shaulian,Karin M. AP-1 as a regulator of cell life and death [J]. Nat Cell Biol, 2002, 4 (5):426-436.
[46] Song BQ, Chi Y, Li X, et al. Inhibition of Notch signaling promotes the adipogenic differentiation of mesenchymal stem cells through autophagy activation and PTEN-PI3K/AKT pathway [J]. Cell Physiol Biochem, 2015,36 (8):1991-2002.
[47] Wang JJ, Zhang XH, Zhu JD, et al. Effects of DAPT on learning and memory abilities and the regulation of Notch signaling pathway in cerebral ischemia-reperfusion injury mice [J]. Acta Anatomica Sinica, 2018, 49 (2): 151-157. (in Chinese)
王俊婕, 张先虎, 朱俊德, 等. DAPT对脑缺血再灌注损伤小鼠学习记忆的影响以及Notch信号通路的调节作用 [J]. 解剖学报, 2018, 49 (2): 151-157. 
[48] Shi Y, Shu B, Yang RH, et al. Expression and effect of Wnt and Notch signaling in mammalian cutaneous wound healing [J]. Chinese Journal of Injury Repair and Wound Healing (Electronic Edition),2014,9 (2):151-157. (in Chinese)
施彦,舒斌,杨荣华,等.Wnt和Notch信号通路在大鼠创面愈合模型中的表达作用[J].中华损伤与修复杂志(电子版), 2014,9(2):151-157. 
[49] Ongaro A,PeHati A,Bagheri L,et al.Characterization of Notch signaling during osteogenic differentiation in human osteosarcoma cell line MG63 [J]. J Cell Physiol, 2016, 231(12):2652-2663.
[50] Schilling T, Ebert R, Raaijmakers N, et al. Effects of phytoestrogens and other plant-derived compounds on mesenchymal stem cells, bone maintenance and regeneration [J]. J Steroid Biochem, 2014, 139(8): 252-261.  

基金

RUNX2-miR320a-BMP6以前馈环模式调控人类成骨细胞分化的机制研究;环状RNAFGFR1/miR-6756-5p/ FASN轴向调控脂肪细胞早期分化过程机制研究;miR-604 靶向作用 MIER1 调控成骨细胞分化的机制研究

PDF(997 KB)

Accesses

Citation

Detail

段落导航
相关文章

/