Biomechanical Effects of Mechanical Stress on Cells Involved in Fracture Healing

Weiyong Wu , Zhihui Zhao , Yongqing Wang , Gengbao Zhu , Kemeng Tan , Meiyue Liu , Lili Li

Orthopaedic Surgery ›› 2024, Vol. 16 ›› Issue (4) : 811 -820.

PDF
Orthopaedic Surgery ›› 2024, Vol. 16 ›› Issue (4) :811 -820. DOI: 10.1111/os.14026
REVIEW ARTICLE

Biomechanical Effects of Mechanical Stress on Cells Involved in Fracture Healing

Author information +
History +
PDF

Abstract

Fracture healing is a complex staged repair process in which the mechanical environment plays a key role. Bone tissue is very sensitive to mechanical stress stimuli, and the literature suggests that appropriate stress can promote fracture healing by altering cellular function. However, fracture healing is a coupled process involving multiple cell types that balance and limit each other to ensure proper fracture healing. The main cells that function during different stages of fracture healing are different, and the types and molecular mechanisms of stress required are also different. Most previous studies have used a single mechanical stimulus on individual mechanosensitive cells, and there is no relatively uniform standard for the size and frequency of the mechanical stress. Analyzing the mechanisms underlying the effects of mechanical stimulation on the metabolic regulation of signaling pathways in cells such as in bone marrow mesenchymal stem cells (BMSCs), osteoblasts, chondrocytes, and osteoclasts is currently a challenging research hotspot. Grasping how stress affects the function of different cells at the molecular biology level can contribute to the refined management of fracture healing. Therefore, in this review, we summarize the relevant literature and describe the effects of mechanical stress on cells associated with fracture healing, and their possible signaling pathways, for the treatment of fractures and the further development of regenerative medicine.

Keywords

Bone marrow mesenchymal stem cells / Fracture healing / Fracture microenvironment / Mechanical stress / Osteoblast

Cite this article

Download citation ▾
Weiyong Wu, Zhihui Zhao, Yongqing Wang, Gengbao Zhu, Kemeng Tan, Meiyue Liu, Lili Li. Biomechanical Effects of Mechanical Stress on Cells Involved in Fracture Healing. Orthopaedic Surgery, 2024, 16(4): 811-820 DOI:10.1111/os.14026

登录浏览全文

4963

注册一个新账户 忘记密码

References

[1]

RauschV, Seybold D, KönigshausenM, KöllerM, SchildhauerTA, Geßmann J. Basic principles of fracture healing. Orthopade. 2017;46:640–647.

[2]

AugatP, Hollensteiner M, von RüdenC. The role of mechanical stimulation in the enhancement of bone healing. Injury. 2021;52(Suppl 2):S78–S83.

[3]

Bigham-SadeghA, OryanA. Basic concepts regarding fracture healing and the current options and future directions in managing bone fractures. Int Wound J. 2015;12:238–247.

[4]

BahneyCS, Zondervan RL, AllisonP, TheologisA, AshleyJW, AhnJ, et al. Cellular biology of fracture healing. J Orthop Res. 2019;37:35–50.

[5]

ChoyM, WongR, ChowS, Li MC, ChimYN, LiTK, et al. How much do we know about the role of osteocytes in different phases of fracture healing? a systematic review. J Orthop Translat. 2020;21:111–121.

[6]

WolffJ. The classic: on the inner architecture of bones and its importance for bone growth. 1870. Clin Orthop Relat Res. 2010;468:1056–1065.

[7]

WangL, YouX, LotinunS, Zhang L, WuN, ZouW. Mechanical sensing protein PIEZO1 regulates bone homeostasis via osteoblast-osteoclast crosstalk. Nat Commun. 2020;11:282.

[8]

GlattV, EvansCH, TetsworthK. A concert between biology and biomechanics: the influence of the mechanical environment on bone healing. Front Physiol. 2016;7:678.

[9]

Osagie-ClouardL, Sanghani-Kerai A, CoathupM, MeesonR, BriggsT, BlunnG. The influence of parathyroid hormone 1-34 on the osteogenic characteristics of adipose- and bone-marrow-derived mesenchymal stem cells from juvenile and ovarectomized rats. Bone Joint Res. 2019;8:397–404.

[10]

Granero-MoltóF, Weis JA, MigaMI, LandisB, MyersTJ, O'RearL, et al. Regenerative effects of transplanted mesenchymal stem cells in fracture healing. Stem Cells. 2009;27:1887–1898.

[11]

KitaoriT, ItoH, SchwarzEM, Tsutsumi R, YoshitomiH, OishiS, et al. Stromal cell-derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model. Arthritis Rheum. 2009;60:813–823.

[12]

LiangX, HuangX, ZhouY, Jin R, LiQ. Mechanical stretching promotes skin tissue regeneration via enhancing mesenchymal stem cell homing and transdifferentiation. Stem Cells Transl Med. 2016;5:960–969.

[13]

WeiFY, LeungKS, LiG, QinJ, ChowSKH, Huang S, et al. Low intensity pulsed ultrasound enhanced mesenchymal stem cell recruitment through stromal derived factor-1 signaling in fracture healing. PloS One. 2014;9:e106722.

[14]

WeiFY, ChowSK, LeungKS, et al. Low-magnitude high-frequency vibration enhanced mesenchymal stem cell recruitment in osteoporotic fracture healing through the SDF-1/CXCR4 pathway. Eur Cell Mater. 2016;31:341–354.

[15]

ZhangB, LuoQ, ChenZ, Sun J, XuB, JuY, et al. Cyclic mechanical stretching promotes migration but inhibits invasion of rat bone marrow stromal cells. Stem Cell Res. 2015;14:155–164.

[16]

YuanL, Sakamoto N, SongG, SatoM. Migration of human mesenchymal stem cells under low shear stress mediated by mitogen-activated protein kinase signaling. Stem Cells Dev. 2012;21:2520–2530.

[17]

RiesC, EgeaV, KarowM, Kolb H, JochumM, NethP. MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines. Blood. 2007;109:4055–4063.

[18]

KasperG, Glaeser JD, GeisslerS, OdeA, Tuischer J, MatziolisG, et al. Matrix metalloprotease activity is an essential link between mechanical stimulus and mesenchymal stem cell behavior. Stem Cells. 2007;25:1985–1994.

[19]

XiaP, ShiY, WangX, Li X. Advances in the application of low-intensity pulsed ultrasound to mesenchymal stem cells. Stem Cell Res Ther. 2022;13:214.

[20]

LuuYK, Capilla E, RosenCJ, GilsanzV, PessinJE, JudexS, et al. Mechanical stimulation of mesenchymal stem cell proliferation and differentiation promotes osteogenesis while preventing dietary-induced obesity. J Bone Miner Res. 2009;24:50–61.

[21]

StewartS, Darwood A, MasourosS, HigginsC, Ramasamy A. Mechanotransduction in osteogenesis. Bone Joint Res. 2020;9:1–14.

[22]

YourekG, Mccormick SM, MaoJJ, ReillyGC. Shear stress induces osteogenic differentiation of human mesenchymal stem cells. Regen Med. 2010;5:713–724.

[23]

VetschJR, BettsDC, MüllerR, HofmannS. Flow velocity-driven differentiation of human mesenchymal stromal cells in silk fibroin scaffolds: a combined experimental and computational approach. PloS One. 2017;12:e180781.

[24]

YamadaS, YassinMA, TorelliF, Hansmann J, GreenJBA, SchwarzT, et al. Unique osteogenic profile of bone marrow stem cells stimulated in perfusion bioreactor is rho-ROCK-mediated contractility dependent. Bioeng Transl Med. 2023;8:e10509.

[25]

LiuL, YuB, ChenJ, Tang Z, ZongC, ShenD, et al. Different effects of intermittent and continuous fluid shear stresses on osteogenic differentiation of human mesenchymal stem cells. Biomech Model Mechanobiol. 2012;11:391–401.

[26]

ChenJC, JacobsCR. Mechanically induced osteogenic lineage commitment of stem cells. Stem Cell Res Ther. 2013;4:107.

[27]

KearneyEM, Farrell E, PrendergastPJ, CampbellVA. Tensile strain as a regulator of mesenchymal stem cell osteogenesis. Ann Biomed Eng. 2010;38:1767–1779.

[28]

WuY, ZhangX, ZhangP, Fang B, JiangL. Intermittent traction stretch promotes the osteoblastic differentiation of bone mesenchymal stem cells by the ERK1/2-activated Cbfa1 pathway. Connect Tissue Res. 2012;53:451–459.

[29]

LuY, ZhaoQ, LiuY, ZhangL, LiD, ZhuZ, et al. Vibration loading promotes osteogenic differentiation of bone marrow-derived mesenchymal stem cells via p38 MAPK signaling pathway. J Biomech. 2018;71:67–75.

[30]

JiangM, ShenQ, ZhouY, Ren W, ChaiM, ZhouY, et al. Fluid shear stress and endothelial cells synergistically promote osteogenesis of mesenchymal stem cells via integrin β1-FAK-ERK1/2 pathway. Turk J Biol. 2021;45:683–694.

[31]

HeinerDE, MeyerMH, FrickSL, Kellam JF, FiechtlJ, MeyerRJ. Gene expression during fracture healing in rats comparing intramedullary fixation to plate fixation by DNA microarray. J Orthop Trauma. 2006;20:27–38.

[32]

HaseebA, KcR, AngelozziM, De Charleroy C, RuxD, TowerRJ, et al. SOX9 keeps growth plates and articular cartilage healthy by inhibiting chondrocyte dedifferentiation/osteoblastic redifferentiation. Proc Natl Acad Sci U S A. 2021;118:e2019152118.

[33]

WangYK, ChenCS. Cell adhesion and mechanical stimulation in the regulation of mesenchymal stem cell differentiation. J Cell Mol Med. 2013;17:823–832.

[34]

MiyanishiK, Trindade MC, LindseyDP, et al. Effects of hydrostatic pressure and transforming growth factor-beta 3 on adult human mesenchymal stem cell chondrogenesis in vitro. Tissue Eng. 2006;12:1419–1428.

[35]

AngeleP, YooJU, SmithC, Mansour J, JepsenKJ, NerlichM, et al. Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro. J Orthop Res. 2003;21:451–457.

[36]

LuJ, FanY, GongX, Zhou X, YiC, ZhangY, et al. The lineage specification of mesenchymal stem cells is directed by the rate of fluid shear stress. J Cell Physiol. 2016;231:1752–1760.

[37]

SchättiO, GradS, GoldhahnJ, et al. A combination of shear and dynamic compression leads to mechanically induced chondrogenesis of human mesenchymal stem cells. Eur Cell Mater. 2011;22:214–225.

[38]

ClaesL, Recknagel S, IgnatiusA. Fracture healing under healthy and inflammatory conditions. Nat Rev Rheumatol. 2012;8:133–143.

[39]

RadyD, AbbassM, El-RashidyAA, et al. Mesenchymal stem/progenitor cells: the prospect of human clinical translation. Stem Cells Int. 2020;2020:8837654.

[40]

WoodcockEM, GirvanP, EckertJ, Lopez-Duarte I, KubánkováM, Van LoonJJWA, et al. Measuring intracellular viscosity in conditions of hypergravity. Biophys J. 2019;116:1984–1993.

[41]

LiuP, TuJ, WangW, Li Z, LiY, YuX, et al. Effects of mechanical stress stimulation on function and expression mechanism of osteoblasts. Front Bioeng Biotechnol. 2022;10:830722.

[42]

GuoY, WangY, LiuY, et al. MicroRNA-218, microRNA-191*, microRNA-3070a and microRNA-33 are responsive to mechanical strain exerted on osteoblastic cells. Mol Med Rep. 2015;12:3033–3038.

[43]

DuD, Furukawa KS, UshidaT. 3D culture of osteoblast-like cells by unidirectional or oscillatory flow for bone tissue engineering. Biotechnol Bioeng. 2009;102:1670–1678.

[44]

WangX, GengB, WangH, Wang S, ZhaoD, HeJ, et al. Fluid shear stress-induced down-regulation of microRNA-140-5p promotes osteoblast proliferation by targeting VEGFA via the ERK5 pathway. Connect Tissue Res. 2022;63:156–168.

[45]

MamounJ. Dry socket etiology, diagnosis, and clinical treatment techniques. J Korean Assoc Oral Maxillofac Surg. 2018;44:52–58.

[46]

DuanZW, LuH. Effect of mechanical strain on cells involved in fracture healing. Orthop Surg. 2021;13:369–375.

[47]

TripuwabhrutP, Mustafa M, GjerdeCG, BrudvikP, Mustafa K. Effect of compressive force on human osteoblast-like cells and bone remodelling: an in vitro study. Arch Oral Biol. 2013;58:826–836.

[48]

GogaY, ChibaM, ShimizuY, Mitani H. Compressive force induces osteoblast apoptosis via caspase-8. J Dent Res. 2006;85:240–244.

[49]

LiP, XuJ, LiuL, ZhangY, LiuM, FanY. Promoting proliferation and differentiation of pre-osteoblasts MC3T3-E1 cells under combined mechanical and electrical stimulation. J Biomed Nanotechnol. 2019;15:921–929.

[50]

WangL, ZhangX, GuoY, ChenX, LiR, LiuL, et al. Involvement of BMPs/Smad signaling pathway in mechanical response in osteoblasts. Cell Physiol Biochem. 2010;26:1093–1102.

[51]

WongM, Siegrist M, GoodwinK. Cyclic tensile strain and cyclic hydrostatic pressure differentially regulate expression of hypertrophic markers in primary chondrocytes. Bone. 2003;33:685–693.

[52]

ZhangT, WenF, WuY, GohGSH, GeZ, TanLP, et al. Cross-talk between TGF-beta/SMAD and integrin signaling pathways in regulating hypertrophy of mesenchymal stem cell chondrogenesis under deferral dynamic compression. Biomaterials. 2015;38:72–85.

[53]

MichalopoulosE, KnightRL, KorossisS, Kearney JN, FisherJ, InghamE. Development of methods for studying the differentiation of human mesenchymal stem cells under cyclic compressive strain. Tissue Eng Part C Methods. 2012;18:252–262.

[54]

CarterDR, WongM. Modelling cartilage mechanobiology. Philos Trans R Soc Lond B Biol Sci. 2003;358:1461–1471.

[55]

JinY, LiZ, WuY, LiH, LiuZ, LiuL, et al. Aberrant fluid shear stress contributes to articular cartilage pathogenesis via epigenetic regulation of ZBTB20 by H3K4me3. J Inflamm Res. 2021;14:6067–6083.

[56]

GeX, ShiR, MaX. The secreted protein WNT5A regulates condylar chondrocyte proliferation, hypertrophy and migration. Arch Oral Biol. 2017;82:171–179.

[57]

RenH, YangH, XieM, WenY, LiuQ, LiX, et al. Chondrocyte apoptosis in rat mandibular condyles induced by dental occlusion due to mitochondrial damage caused by nitric oxide. Arch Oral Biol. 2019;101:108–121.

[58]

ZhouX, von der Mark K, HenryS, NortonW, AdamsH, de CrombruggheB. Chondrocytes transdifferentiate into osteoblasts in endochondral bone during development, postnatal growth and fracture healing in mice. PLoS Genet. 2014;10:e1004820.

[59]

AghajanianP, MohanS. The art of building bone: emerging role of chondrocyte-to-osteoblast transdifferentiation in endochondral ossification. Bone Res. 2018;6:19.

[60]

WongSA, HuDP, SlocumJ, Lam C, NguyenM, MiclauT, et al. Chondrocyte-to-osteoblast transformation in mandibular fracture repair. J Orthop Res. 2021;39:1622–1632.

[61]

QinL, HeT, ChenS, Yang D, YiW, CaoH, et al. Roles of mechanosensitive channel Piezo1/2 proteins in skeleton and other tissues. Bone Res. 2021;9:44.

[62]

XuX, LiuS, LiuH, RuK, JiaY, WuZ, et al. Piezo channels: awesome mechanosensitive structures in cellular mechanotransduction and their role in bone. Int J Mol Sci. 2021;22:6429.

[63]

LiC, DuY, ZhangT, et al. “Genetic scissors” CRISPR/Cas9 genome editing cutting-edge biocarrier technology for bone and cartilage repair. Bioact Mater. 2023;22:254–273.

[64]

NabaviN, Khandani A, CamirandA, HarrisonRE. Effects of microgravity on osteoclast bone resorption and osteoblast cytoskeletal organization and adhesion. Bone. 2011;49:965–974.

[65]

WangQ, DuanM, LiaoJ, Xie J, ZhouC. Are osteoclasts mechanosensitive cells? J Biomed Nanotechnol. 2021;17:1917–1938.

[66]

MaC, GengB, ZhangX, Li R, YangX, XiaY. Fluid shear stress suppresses osteoclast differentiation in RAW264.7 cells through extracellular signal-regulated kinase 5 (ERK5) signaling pathway. Med Sci Monit. 2020;26:e918370.

[67]

RubinJ, MurphyT, NanesMS, Fan X. Mechanical strain inhibits expression of osteoclast differentiation factor by murine stromal cells. Am J Physiol Cell Physiol. 2000;278:C1126–C1132.

[68]

XiaoD, ZhouQ, BaiY, CaoB, ZhangQ, Zeng G, et al. Deficiency of PDK1 in osteoclasts delays fracture healing and repair. Mol Med Rep. 2020;22:1536–1546.

[69]

MuschterD, Beiderbeck AS, SpäthT, KirschneckC, Schröder A, GrässelS. Sensory neuropeptides and their receptors participate in Mechano-regulation of murine macrophages. Int J Mol Sci. 2019;20:503.

[70]

ArgentatiC, MorenaF, TortorellaI, Bazzucchi M, PorcellatiS, EmilianiC, et al. Insight into mechanobiology: how stem cells feel mechanical forces and orchestrate biological functions. Int J Mol Sci. 2019;20:5337.

[71]

BouzidT, KimE, RiehlBD, Esfahani AM, RosenbohmJ, YangR, et al. The LINC complex, mechanotransduction, and mesenchymal stem cell function and fate. J Biol Eng. 2019;13:68.

[72]

NaqviSM, Mcnamara LM. Stem cell mechanobiology and the role of biomaterials in governing Mechanotransduction and matrix production for tissue regeneration. Front Bioeng Biotechnol. 2020;8:597661.

[73]

Delaine-SmithRM, ReillyGC. Mesenchymal stem cell responses to mechanical stimuli. Muscles Ligaments Tendons J. 2012;2:169–180.

[74]

StewardAJ, KellyDJ. Mechanical regulation of mesenchymal stem cell differentiation. J Anat. 2015;227:717–731.

[75]

CharrasG, YapAS. Tensile forces and Mechanotransduction at cell-cell junctions. Curr Biol. 2018;28:R445–R457.

[76]

MartinoF, Perestrelo AR, VinarskýV, PagliariS, ForteG. Cellular Mechanotransduction: from tension to function. Front Physiol. 2018;9:824.

[77]

RosaN, SimoesR, MagalhãesFD, MarquesAT. From mechanical stimulus to bone formation: a review. Med Eng Phys. 2015;37:719–728.

[78]

ZhouT, GaoB, FanY, LiuY, FengS, Cong Q, et al. Piezo1/2 mediate mechanotransduction essential for bone formation through concerted activation of NFAT-YAP1-ß-catenin. Elife. 2020;9:e52779.

[79]

WangL, WangX, JiN, LiHM, CaiSX. Mechanisms of the mechanically activated ion channel Piezo1 protein in mediating osteogenic differentiation of periodontal ligament stem cells via the notch signaling pathway. Hua Xi Kou Qiang Yi Xue Za Zhi. 2020;38:628–636.

[80]

DavenportJR, YoderBK. An incredible decade for the primary cilium: a look at a once-forgotten organelle. Am J Physiol Renal Physiol. 2005;289:F1159–F1169.

[81]

WhitfieldJF. Primary cilium: is it an osteocyte's strain-sensing flowmeter? J Cell Biochem. 2003;89:233–237.

[82]

HoeyDA, KellyDJ, JacobsCR. A role for the primary cilium in paracrine signaling between mechanically stimulated osteocytes and mesenchymal stem cells. Biochem Biophys Res Commun. 2011;412:182–187.

[83]

HarrisAR, JreijP, FletcherDA. Mechanotransduction by the Actin cytoskeleton: converting mechanical stimuli into biochemical signals. Annu Rev Biophys. 2016;47:617–631.

[84]

KounakisK, Tavernarakis N. The cytoskeleton as a modulator of aging and neurodegeneration. Adv Exp Med Biol. 2019;1178:227–245.

[85]

McbeathR, PironeDM, NelsonCM, Bhadriraju K, ChenCS. Cell shape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment. Dev Cell. 2004;6:483–495.

[86]

ShivashankarGV. Mechanical regulation of genome architecture and cell-fate decisions. Curr Opin Cell Biol. 2019;56:115–121.

[87]

MichaelM, Parsons M. New perspectives on integrin-dependent adhesions. Curr Opin Cell Biol. 2020;63:31–37.

[88]

KongL, WangB, YangX, He B, HaoD, YanL. Integrin-associated molecules and signalling cross talking in osteoclast cytoskeleton regulation. J Cell Mol Med. 2020;24:3271–3281.

[89]

LachowskiD, CortesE, RobinsonB, Rice A, RomboutsK, Del Río HernándezAE. FAK controls the mechanical activation of YAP, a transcriptional regulator required for durotaxis. FASEB J. 2018;32:1099–1107.

[90]

MichaelKE, Dumbauld DW, BurnsKL, HanksSK, García AJ. Focal adhesion kinase modulates cell adhesion strengthening via integrin activation. Mol Biol Cell. 2009;20:2508–2519.

[91]

ZhouJ, Aponte-Santamaría C, SturmS, BullerjahnJT, Bronowska A, GräterF. Mechanism of focal adhesion kinase Mechanosensing. PLoS Comput Biol. 2015;11:e1004593.

[92]

JungO, ChoiS, JangSB, Lee SA, LimST, ChoiYJ, et al. Tetraspan TM4SF5-dependent direct activation of FAK and metastatic potential of hepatocarcinoma cells. J Cell Sci. 2012;125:5960–5973.

RIGHTS & PERMISSIONS

2024 The Authors. Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.

AI Summary AI Mindmap
PDF

387

Accesses

0

Citation

Detail

Sections
Recommended

AI思维导图

/