生物力学作用对骨髓间充质干细胞增殖和成骨分化影响研究进展

doi:10.3976/j.issn.1002-4026.2021.02.009

山东科学 ›› 2021, Vol. 34 ›› Issue (2): 65-74.doi: 10.3976/j.issn.1002-4026.2021.02.009

生物力学作用对骨髓间充质干细胞增殖和成骨分化影响研究进展

曹盛楠^1，2a,2b，师彬^2a,2b，孙国栋^3,4，王从安^2a,2b，王丹丹^2a,2b*

1.山东中医药大学针炙推拿学院，山东济南 250353； 2.山东第一医科大学（山东省医学科学院）a.山东第一医科大学附属颈肩腰腿痛医院；b.山东省医药生物技术研究中心山东省骨生物力学工程实验室，山东济南 250012；3.山东第一医科大学第三附属医院，山东济南 250062；4. 天津大学医学工程与转化医学研究院，天津 300072

收稿日期:2020-05-19 出版日期:2021-04-13 发布日期:2021-04-14
通信作者: 王丹丹（1985—），女，硕士生导师，助理研究员，研究方向为骨生物力学。E-mail: 158wdd@163.com E-mail:feiyan.70172@qq.com
作者简介:曹盛楠（1992—），女，博士研究生，研究方向为骨生物力学。E-mail:feiyan.70172@qq.com
基金资助:
泰山学者特聘专家计划（ts201511074）；山东省自然科学基金面上项目（ZR2019MH134）；中国博士后科学基金（2019M662420）；山东省自然科学基金面上项目（ZR2018LH019）；山东省重点研发计划（2016GSF202042）；山东省医学科学院科技计划面上项目（2018-23）；山东省中医药科技发展计划（2019-0543，2019-0545）；山东第一医科大学学术提升计划（2019QL003）

Research progress on the effect of biomechanics on proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells

CAO Sheng-nan^1,2a,2b, SHI Bin^2a,2b，SUN Guo-dong^3,4, WANG Cong-an^2a,2b, WANG Dan-dan^2a,2b*

1.School of Acupunchure-Tuina,Shandong Univeristy of Traditional Chinese Medicine, Jinan 250355, China; 2.a. Neck-Shoulder and Lumbocrural Pain Hospital of Shandong First Medical University; b. Bone Biomechanics Engineering Laboratory of Shandong Province,Shandong Medicinal Biotechnology Center, Shandong First Medical University Shandong Academy of Medical Sciences, Jinan 250012, China; 3. The Third Affiliated Hospital of Shandong Academy of Shandong First Medical University,Jinan 250062, China; 4. Academy of Medical Engineering and Translational Medicine, Tianjin University, Tianjin 300072, China

Received:2020-05-19 Online:2021-04-13 Published:2021-04-14

摘要/Abstract

摘要： 骨髓间充质干细胞在体内所处的力学环境比较复杂，为了探索生物力学与骨髓间充质干细胞增殖分化之间的关系，对近年来生物力学微环境对骨髓间充质干细胞增殖分化影响的研究现状和最新进展进行了综述。认为牵张力与流体剪切力对骨髓间充质干细胞产生的刺激大部分会使其向成骨方向分化，而较大的压缩力和静水压力对骨髓间充质干细胞产生的刺激大部分会使其偏向软骨方向分化，小部分向成骨方向分化，每种分化方向都有其最适的分化条件。通过综述生物力学对骨髓间充质干细胞增殖及成骨分化的影响，为骨髓间充质干细胞的骨组织工程与再生医学研究及更好地应用于临床治疗提供思路和参考依据。

关键词: 骨髓间充质干细胞, 生物力学, 增殖, 分化

Abstract: The biomechanical environment of bone marrow mesenchymal stem cells (BMSCs) in vivo is relatively complex. To explore the relationship between biomechanics and the proliferation and osteogenic differentiation of BMSC, This review summarizes the current research status and latest progress of the effects of biomechanical microenvironment on the proliferation and differentiation of bone marrow mesenchymal sterm cells in recent years.Results showed that mechanical tension stress and fluid shear stress on BMSCs generated most of the stimuli to direct cell differentiation and that larger compression force and static water pressure on BMSCs generated most of the stimuli to direct cells toward cartilage differentiation and a minority of cells toward osteogenic differentiation. Cell differentiation in each direction occurred under its optimal conditions. Here we reviewed the effects of biomechanics on proliferation and osteogenic differentiation of BMSC, which may provide insights and references for research on bone tissue engineering, regenerative medicine, and clinical applications of BMSCs.

Key words: bone marrow mesenchymal stem cells, biomechanics, proliferation, osteogenic differentiation

中图分类号:

曹盛楠, 师彬, 孙国栋, 王从安, 王丹丹. 生物力学作用对骨髓间充质干细胞增殖和成骨分化影响研究进展[J]. 山东科学, 2021, 34(2): 65-74.

CAO Sheng-nan, SHI Bin, SUN Guo-dong, WANG Cong-an, WANG Dan-dan. Research progress on the effect of biomechanics on proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells[J]. Shandong Science, 2021, 34(2): 65-74.

参考文献 51

1	李婷, 陈莉智, 黄文华. 骨髓间充质干细胞在基础医学及临床应用中的研究进展[J]. 中国医学物理学杂志, 2019,36(8): 962-967. doi: 10.3969/j.issn.1005-202X.2019.08.019
2	MOHAMED-AHMED S, FRISTAD I, LIE S A, et al. Adipose-derived and bone marrow mesenchymal stem cells: a donor-matched comparison[J]. Stem Cell Research & Therapy, 2018, 9: 168. doi: 10.1186/s13287-018-0914-1
3	WANG Y K, CHEN C S. Cell adhesion and mechanical stimulation in the regulation of mesenchymal stem cell differentiation[J]. Journal of Cellular and Molecular Medicine, 2013, 17(7): 823-832. doi: 10.1111/jcmm.12061
4	LIU Y S, LEE O K. In search of the pivot point of mechanotransduction:Mechanosensing of stem cells[J]. Cell Transplantation, 2014, 23(1): 1-11. doi: 10.3727/096368912X659925
5	YIM E K, SHEETZ M P. Force-dependent cell signaling in stemcell differentiation[J]. Stem Cell Research & Therapy, 2012, 3(5): 1-12. doi: 10.1186/scrt132
6	STEWARD A J, KELLY D J. Mechanical regulation ofmesenchymal stem cell differentiation[J]. Journal of Anatomy, 2015, 227(6): 717-731. doi: 10.1111/joa.12243
7	ZENG Z B, YIN X, ZHANG X D, et al. Cyclic stretch enhances bone morphogenetic protein-2-induced osteoblastic differentiation through the inhibition of Hey1[J]. International Journal of Molecular Medicine, 2015, 36(5): 1273-1281. doi: 10.3892/ijmm.2015.2354
8	胡晓磐, 达忱, 黄东洋, 等. 周期性机械牵张刺激对C2C12小鼠成肌细胞增殖和有氧代谢能力的影响[J]. 医用生物力学, 2016, 31(2): 112-116. doi: 10.3871/j.1004-7220.2016.02.112
9	黎润光, 邵景范, 魏明发, 等. 牵张应力对人骨髓间充质干细胞增殖及细胞周期的影响[J]. 中国组织工程研究与临床康复, 2007, 11(7): 1247-1251. doi: 10.3321/j.issn:1673-8225.2007.07.012
10	井燕, 李良, 李毅, 等. 力学应变对大鼠骨髓间充质干细胞增殖和成骨分化能力的影响[J]. 生物医学工程学杂志, 2006, 23(3): 542-545. doi: 10.3321/j.issn:1001-5515.2006.03.018
11	戚孟春, 梁永强, 孙红, 等. 张应力下成骨性转录因子在骨髓间充质干细胞中的表达[J]. 实用口腔医学杂志, 2008, 24(5): 654-658. doi: 10.3969/j.issn.1001-3733.2008.05.010
12	高莺, 李继华, 韩立赤, 等. 张应力诱导大鼠骨髓间充质干细胞骨向分化及其差异基因表达分析[J]. 华西口腔医学杂志, 2009, 27(2): 213-216.
13	薛令法, 张岱尊, 肖文林, 等. 机械牵张力促进小鼠骨髓间充质干细胞的成骨向分化[J]. 国际口腔医学杂志, 2017, 44(6): 679-685. doi: 10.7518/gjkq.2017.06.011
14	WU J J, ZHAO J, SUN L, et al. Long non-coding RNA H19 mediates mechanical tension-induced osteogenesis of bone marrow mesenchymal stem cells via FAK by sponging miR-138[J]. Bone, 2018, 108: 62-70. doi: 10.1016/j.bone.2017.12.013
15	JANG J Y, LEE S W, PARK S H, et al. Combined effects of surface morphology and mechanical straining magnitudes on the differentiation of mesenchymal stem cells without using biochemical reagents[J].Journal of Biomedicine and Biotechnology, 2011, 2011: 1-9. doi: 10.1155/2011/860652
16	SONG G B, JU Y, SHEN X D, et al. Mechanical stretch promotes proliferation of rat bone marrow mesenchymal stem cells[J]. Colloids and Surfaces B: Biointerfaces, 2007, 58(2): 271-277. DOI:10.1016/j.colsurfb.2007.04.001.
17	ELDER S H, SANDERS S W, MCCULLEY W R, et al. Chondrocyte response to cyclic hydrostatic pressure in alginate versus pellet culture[J]. Journal of Orthopaedic Research, 2006, 24(4): 740-747. DOI:10.1002/jor.20086.
18	CAMPBELL J J, LEE D A, BADER D L. Dynamic compressive strain influences chondrogenic gene expression in human mesenchymal stem cells[J]. Biorheology, 2006, 43(3/4): 455-470.
19	刘岩正, 陈慧, 杜静, 等. 压力对大鼠BMSCs增殖及成软骨能力影响[J]. 牙体牙髓牙周病学杂志, 2013, 23(4): 225-230. doi: 10.15956/j.cnki.chin.j.conserv.dent.2013.04.003
20	何川, 邓廉夫, 杨庆铭, 等. 静水压力刺激对人骨髓间充质干细胞成骨、成脂双向分化的影响[J]. 中华骨科杂志, 2008, 28(5): 397-401. doi: 10.3321/j.issn:0253-2352.2008.05.010
21	李正章, 程应樟, 吴险峰, 等. 周期性压力培养对免骨髓间充质干细胞增殖的影响[J]. 中国组织工程研究与临床康复, 2009, 13(19): 3628-3632. doi: 10.3969/j.issn.1673-8225.2009.19.005
22	潘景光, 赵萤, 刘岩正, 等. 周期性流体静压力对BMSCs细胞增殖活性及超微结构的影响[J]. 口腔医学研究, 2017, 33(6): 593-596. doi: 10.13701/j.cnki.kqyxyj.2017.06.004
23	赵永亮, 冯军宇, 王刚, 等. 周期性动态压力对海藻酸钠培养间充质干细胞成软骨分化的作用[J]. 中华关节外科杂志(电子版), 2016, 10(4): 413-418. doi: 10.3877/cma.j.issn.1674-134X.2016.04.010
24	易飞舟,赵萤,张旻.流体压力对骨髓间充质干细胞软骨向分化影响的体外实验研究[J].口腔医学,2016, 36(6): 481-484. doi: 10.13591/j.cnki.kqyx.2016.06.001
25	ARNSDORF E J, TUMMALA P, KWON R Y, et al. Mechanicallyinduced osteogenic differentiation: the role of RhoA, ROCKII and cytoskeletal dynamics[J]. Journal of Cell Science, 2009, 122(Pt 4): 546-553. doi: 10.1242/jcs.036293
26	KAPUR S, BAYLINK D J, WILLIAM LAU K H. Fluid flow shear stress stimulates human osteoblast proliferation and differentiation through multiple interacting and competing signal transduction pathways[J]. Bone, 2003, 32(3): 241-251. doi: 10.1016/S8756-3282(02)00979-1
27	SONAM S, SATHE S R, YIM E K F, et al. Cell contractility arising from topography and shear flow determines human mesenchymal stem cell fate[J]. Scientific Reports, 2016, 6: 20415. doi: 10.1038/srep20415
28	李洪鹏, 许建中, 周强, 等. 流体剪切应力对人骨髓间充质干细胞增值及细胞周期的影响[J]. 第三军医大学学报, 2005, 27(16): 1637-1639. doi: 10.3321/j.issn:1000-5404.2005.16.005
29	李立,朱楚洪,糜建红,等.切应力诱导间充质干细胞分化成内皮细胞的研究[J].局解手术学杂志, 2008, 17(5): 306-308. doi: 10.3969/j.issn.1672-5042.2008.05.004
30	KREKE M R, HUCKLE W R,GOLDSTEIN A S. Fluid flow stimulates expression of osteopontin and bone sialoprotein by bone marrow stromal cells in a temporally dependent manner[J]. Bone, 2005, 36(6): 1047-1055. doi: 10.1016/j.bone.2005.03.008
31	刘立跃. 流体剪切力影响人骨髓间充质干细胞分化的机制研究[D]. 杭州: 浙江大学, 2011.
32	STAVENSCHI E, LABOUR M N, HOEY D A. Oscillatory fluid flow induces the osteogenic lineage commitment of mesenchymal stem cells: The effect of shear stress magnitude, frequency, and duration[J].Journal of Biomechanics, 2017, 55: 99-106. doi: 10.1016/j.jbiomech.2017.02.002
33	HUANG Y, JIA X L, BAI K, et al. Effect of fluid shear stress on cardiomyogenic differentiation of rat bone marrow mesenchymal stem cells[J]. Archives of Medical Research, 2010, 41(7): 497-505. doi: 10.1016/j.arcmed.2010.10.002
34	张成俊, 夏亚一, 王常德. 骨细胞力学信号转导及基因表达[J]. 国际骨科学杂志, 2008,29(3): 182-186. doi: 10.3969/j.issn.1673-7083.2008.03.014
35	孙彬, 段浩, 钟宗雨, 等. 骨髓间充质干细胞对机械力学微环境的响应:观点、现状、思考与未来[J]. 中国组织工程研究, 2019, 23(25): 4075-4081. doi: 10.3969/j.issn.2095-4344.1783
36	SIMMONS C A, MATLIS S, THORNTON A J, et al. Cyclic strain enhances matrix mineralization by adult human mesenchymal stem cells via the extracellular signal-regulated kinase (ERK1/2) signaling pathway[J]. Journal of Biomechanics, 2003, 36(8): 1087-1096. doi: 10.1016/S0021-9290(03)00110-6
37	刘小雅, 肖文林, 于保军. 持续牵张促进小鼠骨髓间充质干细胞成骨向分化机制的研究[J]. 口腔医学研究, 2015, 31(8): 775-778. doi: 10.13701/j.cnki.kqyxyj.2015.08.007
38	赵闯, 周昊, 朱晓文, 等. Wnt/β-catenin信号通路在大鼠骨髓间充质干细胞牵张中的表达[J]. 中国口腔颌面外科杂志, 2013, 11(5): 354-358.
39	WU Y Q, ZHANG X L, ZHANG P, et al. Intermittent traction stretch promotes the osteoblastic differentiation of bone mesenchymal stem cells by the ERK1/2-activated Cbfa1 pathway[J]. Connective Tissue Research, 2012, 53(6): 451-459. doi: 10.3109/03008207.2012.702815
40	HU P, ZHU X W, ZHAO C, et al. Fak silencing impairsosteogenic differentiation of bone mesenchymal stem cells induced by uniaxial mechanical stretch[J]. Journal of Dental Sciences, 2019, 14(3): 225-233. doi: 10.1016/j.jds.2019.03.001
41	杜静, 程百祥, 陈慧, 等. BMPs信号通路在压力调控兔BMSCs成软骨响应中的作用[J]. 牙体牙髓牙周病学杂志, 2013,23(4): 218-224. doi: 10.15956/j.cnki.chin.j.conserv.dent.2013.04.005
42	陈骥, 刘艳丽, 赵寅华, 等. RhoA信号通路在流体静压力调控大鼠BMSCs成骨响应中的作用[J]. 口腔医学研究, 2014, 30(8): 695-698. doi: 10.13701/j.cnki.kqyxyj.2014.08.001
43	易飞舟, 赵萤, 赵寅华, 等. 流体静压力调控下Rac1信号通路在大鼠BMSCs成软骨响应中的作用[J]. 牙体牙髓牙周病学杂志, 2015, 25(6): 335-341. doi: 10.15956/j.cnki.chin.j.conserv.dent.2015.06.002
44	ZHAO Y H, LV X, LIU Y L, et al.Hydrostatic pressure promotes the proliferation and osteogenic/chondrogenic differentiation of mesenchymal stem cells: the roles of RhoA and Rac1[J]. Stem Cell Research, 2015, 14(3): 283-296. doi: 10.1016/j.scr.2015.02.006
45	GRELLIER M, BAREILLE R, BOURGET C,et al. Responsiveness of human bone marrow stromal cells to shear stress[J]. Journal of Tissue Engineering and Regenerative Medicine, 2009, 3(4): 302-309. doi: 10.1002/term.166
46	LIU L Y, SHAO L, LI B, et al. Extracellular signal-regulated kinase1/2 activated by fluid shear stress promotes osteogenic differentiation of human bone marrow-derived mesenchymal stem cells through novel signaling pathways[J]. The International Journal of Biochemistry & Cell Biology, 2011, 43(11): 1591-1601. doi: 10.1016/j.biocel.2011.07.008
47	王颖楠, 赵敏, 徐惠成. 骨髓间充质干细胞与脱细胞基质构建组织工程材料的研究进展[J]. 现代实用医学, 2014, 26(8): 1054-1056. doi: 10.3969/j.issn.1671-0800.2014.08.080
48	ORYAN A, KAMALI A, MOSHIRI A, et al. Role of mesenchymal stem cells in bone regenerative medicine: what is the evidence?[J]. Cells, Tissues, Organs, 2017, 204(2): 59-83. doi: 10.1159/000469704
49	FANG S H, LI Y F, CHEN P. Osteogenic effect of bone marrow mesenchymal stem cell-derived exosomes on steroid-induced osteonecrosis of the femoral head[J]. Drug Design, Development and Therapy, 2018, 13: 45-55. doi: 10.2147/dddt.s178698
50	HUANG C H, CHEN M H, YOUNG T H, et al. Interactive effects of mechanical stretching and extracellular matrix proteins on initiating osteogenic differentiation of human mesenchymal stem cells[J].Journal of Cellular Biochemistry,2009,108(6):1263-1273. doi: 10.1002/jcb.22356
51	ENGLER A J, SEN S, SWEENEY H L, et al. Matrix elasticity directsstem cell lineage specification[J]. Cell, 2006, 126(4): 677-689. doi: 10.1016/j.cell.2006.06.044

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生物力学作用对骨髓间充质干细胞增殖和成骨分化影响研究进展

Research progress on the effect of biomechanics on proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells

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