Mechanical regulation of chondrogenic differentiation of bone marrow mesenchymal cells

doi:10.3969/j.issn.2095-4344.2016.45.022

Abstract

Abstract:

BACKGROUND: Bone marrow mesenchymal cells are ideal seed cells for tissue engineering and cell therapy. We are seeking to improve the cartilage repair strategy based on bone marrow mesenchymal cells in vitro by use of natural mechanical transfer pathways.
OBJECTIVE: To analyze the mechanical factors affecting the fate of bone marrow mesenchymal cells and utilize the mechanical strategy to induce chondrogenesis.
METHODS: The first author retrieved the literature in CNKI, PubMed, Medline and Elsevier databases (1985-2015) with the key words of “mechanical regulation, bone marrow mesenchymal cells, bone marrow mesenchymal stem cells, chondrogenic differentiation, cartilage differentiation”.
RESULTS AND CONCLUSION: Herein, we summarize some latest research results on the mechanical stimulus-induced chondrogenic differentiation of bone marrow mesenchymal cells, discuss the effects of different mechanical stimulations on the chondrogenic differentiation of bone marrow mesenchymal cells, as well as summarize the biological mechanism and signal pathways of the cells in response to mechanical stimulations in the process of chondrogenic differentiation. At last, this paper points out the future prospects of the key problems in this field, such as cartilage regeneration and repair strategy based on chondrogenic differentiation of bone marrow mesenchymal cells under mechanical stimulation.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Mechanics, Cartilage, Tissue Engineering

CLC Number:

R318

Zhang Xiao-mei, Peng Xu, Wei Shi-hang, Shi Xue-ni, Liu Yan, He Xue-ling. Mechanical regulation of chondrogenic differentiation of bone marrow mesenchymal cells[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(45): 6834-6840.

Figures/Tables 1

2.1 骨髓间充质干细胞向软骨细胞分化的过程这是一个多阶段细胞过程，包括细胞的募集、迁移、聚集、浓集以及软骨细胞分化。在这个过程中，细胞形态从扁平伸展状态转变成圆形，细胞间隙开始消失，细胞外基质发生改变以及细胞间的黏附性增加，随之细胞骨架结构发生改变[2-3](图2)。细胞的浓集过程是细胞与细胞以及细胞和细胞外基质之间的相互作用的过程，这些过程可能涉及引起骨髓间充质干细胞软骨细胞分化的信号通路。在细胞浓集前，软骨前体间质细胞产生的细胞外基质富含透明质酸和Ⅰ型以及Ⅲ型胶原。骨髓间充质干细胞浓集的开始伴随透明质酸酶活性增加和细胞黏附分子的出现，如神经钙黏蛋白，以及神经细胞黏附分子[4]。这些细胞分子的下游是细胞内激酶，磷酸酶和小G蛋白。骨形成蛋白和其他生长因子通过这些细胞内信号分子来调节细胞信号。据报道，有丝分裂原激活蛋白激酶(mitogen-activated protein kinase，MAPK)、细胞外信号调节激酶(extracellular signal-regulated kinases 1/2，ERK-1/2)的每一个家族成员能够调节软骨特异性转录增强子Sox9基因的表达，其在间质细胞浓集中表达并能加强Ⅱ型胶原的表达[5]。细胞浓集后，软骨细胞继续分化和成熟。一旦软骨细胞开始成熟，软骨特异性基因Ⅱ型胶原和蛋白聚糖开始表达，并通过产生细胞外基质蛋白来增强分离细胞。在软骨形成过程中，细胞浓集中产生的细胞-细胞外基质和细胞间黏附相继得到释放。随后，肌动蛋白细胞骨架重新组合，细胞变成球形[1]。成熟的软骨细胞通过自身调节细胞外基质的生成平衡，分泌基质金属蛋白酶降解细胞外基质形成软骨陷窝，最后分化为肥大软骨细胞，促进X型胶原和基质钙化。最终在软骨内钙化，软骨被骨骼取代[2]。"

References

[1] 徐百耀,宋关斌.力学刺激诱导骨髓间充质干细胞选择分化的研究进展[J].医用生物力学,2007,22(1):104-108.
[2] Takahashi I, Masuda T, Kohsaka K, et al. Molecular mechanisms of mechanical stress response during chondrogenesis. J Biomech Sci Eng 2009;4(3):307-317.
[3] Angele P, Yoo JU, Smith C, et al. Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro. J Orthop Res. 2003;21(3):451-457.
[4] Toyoda T, Seedhom BB, Kirkham J, et al. Upregulation of aggrecan and type II collagen mRNA expression in bovine chondrocytes by the application of hydrostatic pressure. Biorheology. 2003;40(1-3):79-85.
[5] Tew SR, Peffers MJ, McKay TR, et al. Hyperosmolarity regulates SOX9 mRNA posttranscriptionally in human articular chondrocytes. Am J Physiol Cell Physiol. 2009; 297(4):C898-906.
[6] 刘天一,周广东,苗春雷,等.力学刺激影响猪骨髓基质干细胞体外软骨形成的初步研究[J].中华医学杂志,2004, 84(23):1997-2001.
[7] Elder BD, Athanasiou KA. Synergistic and additive effects of hydrostatic pressure and growth factors on tissue formation. PloS One. 2008;3(6):e2341.
[8] Miyanishi K, Trindade MC, Lindsey DP, et al. Effects of hydrostatic pressure and transforming growth factor-beta 3 on adult human mesenchymal stem cell chondrogenesis in vitro. Tissue Eng. 2006;12(6): 1419-1428.
[9] Wagner DR, Lindsey DP, Li KW, et al. Hydrostatic pressure enhances chondrogenic differentiation of human bone marrow stromal cells in osteochondrogenic medium. Ann Biomed Eng. 2008; 36(5):813-820.
[10] Finger AR, Sargent CY, Dulaney KO, et al. Differential effects on messenger ribonucleic acid expression by bone marrow-derived human mesenchymal stem cells seeded in agarose constructs due to ramped and steady applications of cyclic hydrostatic pressure. Tissue Eng. 2007;13(6):1151-1158.
[11] Puetzer J, Williams J, Gillies A, et al. The effects of cyclic hydrostatic pressure on chondrogenesis and viability of human adipose- and bone marrow-derived mesenchymal stem cells in three-dimensional agarose constructs. Tissue Eng Part A. 2013;19(1-2):299-306.
[12] Li J, Zhao Z, Yang J, et al. p38 MAPK mediated in compressive stress-induced chondrogenesis of rat bone marrow MSCs in 3D alginate scaffolds. J Cell Physiol. 2009 221(3):609-617.
[13] Li J, Wang J, Zou Y, et al. The influence of delayed compressive stress on TGF-β1-induced chondrogenic differentiation of rat BMSCs through Smad-dependent and Smad-independent pathways. Biomaterials. 2012; 33(33):8395-8405.
[14] Urban JP, Hall AC, Gehl KA. Regulation of matrix synthesis rates by the ionic and osmotic environment of articular chondrocytes. J Cell Physiol. 1993;154(2): 262-270.
[15] Hopewell B, Urban JP. Adaptation of articular chondrocytes to changes in osmolality. Biorheology. 2003;40(1-3):73-77.
[16] Negoro K, Kobayashi S, Takeno K, et al. Effect of osmolarity on glycosaminoglycan production and cell metabolism of articular chondrocyte under three-dimensional culture system. Clin Exp Rheumatol. 2008;26(4):534-541.
[17] Xu X, Urban JP, Tirlapur UK, et al. Osmolarity effects on bovine articular chondrocytes during three-dimensional culture in alginate beads. Osteoarthritis Cartilage. 2010;18(3):433-439.
[18] Oswald ES, Ahmed HS, Kramer SP, et al. Effects of hypertonic (NaCl) two-dimensional and three-dimensional culture conditions on the properties of cartilage tissue engineered from an expanded mature bovine chondrocyte source. Tissue Eng Part C Methods. 2011;17(11):1041-1049.
[19] Peffers MJ, Milner PI, Tew SR, et al. Regulation of SOX9 in normal and osteoarthritic equine articular chondrocytes by hyperosmotic loading. Osteoarthritis Cartilage. 2010;18(11):1502-1508.
[20] Wuertz K, Godburn K, Neidlinger-Wilke C, et al. Behavior of mesenchymal stem cells in the chemical microenvironment of the intervertebral disc. Spine (Phila Pa 1976). 2008;33(17):1843-1849.
[21] Liang C, Li H, Tao Y, et al. Responses of human adipose-derived mesenchymal stem cells to chemical microenvironment of the intervertebral disc. J Transl Med. 2012;10:49.
[22] Caron MM, van der Windt AE, Emans PJ, et al. Osmolarity determines the in vitro chondrogenic differentiation capacity of progenitor cells via nuclear factor of activated T-cells 5. Bone. 2013;53(1):94-102.
[23] Lu J, Fan Y, Gong X, et al. The Lineage Specification of Mesenchymal Stem Cells Is Directed by the Rate of Fluid Shear Stress. J Cell Physiol. 2016;231(8): 1752-1760.
[24] Alves da Silva ML, Martins A, Costa-Pinto AR, et al. Chondrogenic differentiation of human bone marrow mesenchymal stem cells in chitosan-based scaffolds using a flow-perfusion bioreactor. J Tissue Eng Regen Med. 2011;5(9):722-732.
[25] Mayer-Wagner S, Hammerschmid F, Redeker JI, et al. Simulated microgravity affects chondrogenesis and hypertrophy of human mesenchymal stem cells. Int Orthop. 2014;38(12):2615-2621.
[26] 吕昌伟,胡蕴玉,崔玉明,等.应力环境下三维诱导组织工程种植细胞修复关节软骨缺损[J].中国矫形外科杂志,2004, 12(1):74-76.
[27] 霍建忠,蒋淳,陈峥嵘.应用微重力旋转培养系统构建组织工程软骨的实验研究[J].中国药物与临床,2008,8(10): 766-769.
[28] Hughes-Fulford M. Signal transduction and mechanical stress. Sci STKE. 2004;2004(249):RE12.
[29] 黎润光,邵景范,魏明发.机械牵张应力对成骨细胞的影响研究进展[J].中国矫形外科杂志,2006,14(6):457-460.
[30] 包志强,任明姬,李建福.干细胞应力学效应机制的研究与进展[J].中国组织工程研究与临床康复,2011,15(1): 143-146.
[31] Takahashi I, Onodera K, Sasano Y, et al. Effect of stretching on gene expression of beta1 integrin and focal adhesion kinase and on chondrogenesis through cell-extracellular matrix interactions. Eur J Cell Biol. 2003;82(4):182-192.
[32] Onodera K, Takahashi I, Sasano Y, et al. Stepwise mechanical stretching inhibits chondrogenesis through cell-matrix adhesion mediated by integrins in embryonic rat limb-bud mesenchymal cells. Eur J Cell Biol. 2005;84(1):45-58.
[33] Somlyo AP, Somlyo AV. Signal transduction by G-proteins, rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II. J Physiol. 2000;522 Pt 2:177-185.
[34] Saha S, Ji L, de Pablo JJ, et al. TGFbeta/Activin/Nodal pathway in inhibition of human embryonic stem cell differentiation by mechanical strain. Biophys J. 2008; 94(10):4123-4133.
[35] 戚孟春,胡静,邹淑娟,等.大鼠骨髓间充质干细胞和颅骨成骨细胞在张应力下细胞骨架的改变[J].华西口腔医学杂志,2005,23(2):110-112.
[36] Arnsdorf EJ, Tummala P, Kwon RY, et al. Mechanically induced osteogenic differentiation--the role of RhoA, ROCKII and cytoskeletal dynamics. J Cell Sci. 2009; 122(Pt 4):546-553.
[37] McBride SH, Knothe Tate ML. Modulation of stem cell shape and fate A: the role of density and seeding protocol on nucleus shape and gene expression. Tissue Eng Part A. 2008;14(9):1561-1572.
[38] Siebers MC, ter Brugge PJ, Walboomers XF, et al. Integrins as linker proteins between osteoblasts and bone replacing materials. A critical review. Biomaterials. 2005;26(2):137-146.
[39] Franceschi RT, Xiao G. Regulation of the osteoblast-specific transcription factor, Runx2: responsiveness to multiple signal transduction pathways. J Cell Biochem. 2003;88(3):446-454.