The function of integrin in bone remodeling

doi:10.3877/cma.j.issn.1674-1366.2021.02.011

Abstract

Abstract:

The process of bone remodeling is an important biological response, which involves various cells including mesenchymal stem cells, osteoblasts, osteocytes and osteoclasts. As an important transmembrane molecule, Integrins regulates a variety of cell functions during this process. Here, we shall briefly review the expression and function of integrins in bone remodeling in order to provide theoretical foundation for follow-up research and clinical application.

Key words: Integrins, Bone remodeling, Cytoskeleton, Mechanotransduction, cellular, Mesenchymal stem cell, Osteoblasts, Osteocytes, Osteoclasts

Huimin Zheng, Xianyou Xia, Meng Liu, Xiaoyu Yao, Lei Sui. The function of integrin in bone remodeling[J]. Chinese Journal of Stomatological Research(Electronic Edition), 2021, 15(02): 124-128.

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References 42

[1]	Jensen PR, Andersen TL, Pennypacker BL，et al. A supra-cellular model for coupling of bone resorption to formation during remodeling：lessons from two bone resorption inhibitors affecting bone formation differently[J]. Biochem Biophys Res Commun，2014，443（2）：694-699. DOI：10.1016/j.bbrc.2013.12.036.
[2]	Erben RG. Hypothesis：Coupling between Resorption and Formation in Cancellous bone Remodeling is a Mechanically Controlled Event[J]. Front Endocrinol（Lausanne），2015，6：82. DOI：10.3389/fendo.2015.00082.
[3]	Cao W, Helder MN, Bravenboer N，et al. Is There a Governing Role of Osteocytes in Bone Tissue Regeneration？[J]. Curr Osteoporos Rep，2020，18（5）：541-550. DOI：10.1007/s11914-020-00610-6.
[4]	Søe K, Delaisse JM, Borggaard XG. Osteoclast formation at the bone marrow/bone surface interface：Importance of structural elements，matrix，and intercellular communication[J]. Semin Cell Dev Biol，2020. DOI：10.1016/j.semcdb.2020.05.016.
[5]	Lee HM, Seo SR, Kim J，et al. Expression dynamics of integrin α2，α3，and αV upon osteogenic differentiation of human mesenchymal stem cells[J]. Stem cell Res Ther，2020，11（1）：210. DOI：10.1186/s13287-020-01714-7.
[6]	Sun Z, Guo SS, Fässler R. Integrin-mediated mechanotransduction[J]. J Cell Biol，2016，215（4）：445-456. DOI：10.1083/jcb.201609037.
[7]	Wang X, Schwartz Z, Gittens RA，et al. Role of integrin α2 β1 in mediating osteoblastic differentiation on three-dimensional titanium scaffolds with submicron-scale texture[J]. J Biomed Mater Res A，2015，103（6）：1907-1918. DOI：10.1002/jbm.a.35323.
[8]	De Franceschi N, Hamidi H, Alanko J，et al. Integrin traffic - the update[J]. J Cell Sci，2015，128（5）：839-852. DOI：10.1242/jcs.161653.
[9]	Geoghegan IP, Hoey DA, Mcnamara LM. Integrins in Osteocyte Biology and Mechanotransduction[J]. Curr Osteoporosis Rep，2019，17（4）：195-206. DOI：10.1007/s11914-019-00520-2.
[10]	Kong L, Wang B, Yang X，et al. Integrin-associated molecules and signalling cross talking in osteoclast cytoskeleton regulation[J]. J Cell Mol Med，2020，24（6）：3271-3281. DOI：10.1111/jcmm.15052.
[11]	Marie PJ, Haÿ E, Saidak Z. Integrin and cadherin signaling in bone：role and potential therapeutic targets[J]. Trends Endocrinol Metab，2014，25（11）：567-575. DOI：10.1016/j.tem.2014.06.009.
[12]	Michael M, Parsons M. New perspectives on integrin-dependent adhesions[J]. Curr Opin Cell Biol，2020，63：31-37. DOI：10.1016/j.ceb.2019.12.008.
[13]	Shie MY, Ding SJ. Integrin binding and MAPK signal pathways in primary cell responses to surface chemistry of calcium silicate cements[J]. Biomaterials，2013，34（28）：6589-6606. DOI：10.1016/j.biomaterials.2013.05.075.
[14]	Uda Y, Azab E, Sun N，et al. Osteocyte Mechanobiology[J]. Curr Osteoporos Rep，2017，15（4）：318-325. DOI：10.1007/s11914-017-0373-0.
[15]	Shin SY, Pozzi A, Boyd SK，et al. Integrin α1β1 protects against signs of post-traumatic osteoarthritis in the female murine knee partially via regulation of epidermal growth factor receptor signalling[J]. Osteoarthritis Cartilage，2016，24（10）：1795-1806. DOI：10.1016/j.joca.2016.05.013.
[16]	Bayer ML, Svensson RB, Schjerling P，et al. Influence of the integrin alpha-1 subunit and its relationship with high-fat diet upon extracellular matrix synthesis in skeletal muscle and tendon[J]. Cell Tissue Res，2020，381（1）：177-187. DOI：10.1007/s00441-020-03184-y.
[17]	Chiu LH, Lai WF, Chang SF，et al. The effect of type Ⅱ collagen on MSC osteogenic differentiation and bone defect repair[J]. Biomaterials，2014，35（9）：2680-2691. DOI：10.1016/j.biomaterials.2013.12.005.
[18]	Lee HJ, Kim SY, Koh JM，et al. Polymorphisms and haplotypes of integrinalpha1（ITGA1）are associated with bone mineral density and fracture risk in postmenopausal Koreans[J]. Bone，2007，41（6）：979-986. DOI：10.1016/j.bone.2007.08.034.
[19]	Adorno-Cruz V, Liu H. Regulation and functions of integrin α2 in cell adhesion and disease[J]. Genes Dis，2019，6（1）：16-24. DOI：10.1016/j.gendis.2018.12.003.
[20]	Becerra-Bayona SM, Guiza-Arguello VR, Russell B，et al. Influence of collagen-based integrin α1 and α2 mediated signaling on human mesenchymal stem cell osteogenesis in three dimensional contexts[J]. J Biomed Mater Res A，2018，106（10）：2594-2604. DOI：10.1002/jbm.a.36451.
[21]	Stange R, Kronenberg D, Timmen M，et al. Age-related bone deterioration is diminished by disrupted collagen sensing in integrin α2β1 deficient mice[J]. Bone，2013，56（1）：48-54. DOI：10.1016/j.bone.2013.05.003.
[22]	Chen C, Jiang Z, Yang G. Laminins in osteogenic differentiation and pluripotency maintenance[J]. Differentiation，2020，114：13-19. DOI：10.1016/j.diff.2020.05.002.
[23]	Peng X, Nelson ES, Maiers JL，et al. New insights into vinculin function and regulation[J]. Int Rev Cell Mol Bio，2011，287：191-231. DOI：10.1016/b978-0-12-386043-9.00005-0.
[24]	Lo YP, Liu YS, Rimando MG，et al. Three-dimensional spherical spatial boundary conditions differentially regulate osteogenic differentiation of mesenchymal stromal cells[J]. Sci Rep，2016，6：21253. DOI：10.1038/srep21253.
[25]	Zheng H, Tian Y, Gao Q，et al. Hierarchical Micro-Nano Topography Promotes Cell Adhesion and Osteogenic Differentiation via Integrin α2-PI3K-AKT Signaling Axis[J]. Front Bioeng Biotechnol，2020，8：463. DOI：10.3389/fbioe.2020.00463.
[26]	Marie PJ. Targeting integrins to promote bone formation and repair[J]. Nat Rev Endocrinol，2013，9（5）：288-295. DOI：10.1038/nrendo.2013.4.
[27]	Salmela M, Jokinen J, Tiitta S，et al. Integrin α2β1 in nonactivated conformation can induce focal adhesion kinase signaling[J]. Sci Rep，2017，7（1）：3414. DOI：10.1038/s41598-017-03640-w.
[28]	Yoon SO, Shin S, Karreth FA，et al. Focal Adhesion- and IGF1R-Dependent Survival and Migratory Pathways Mediate Tumor Resistance to mTORC1/2 Inhibition[J]. Mol Cell，2017，67（3）：512-527.e4. DOI：10.1016/j.molcel.2017.06.033.
[29]	Guan M, Yao W, Liu R，et al. Directing mesenchymal stem cells to bone to augment bone formation and increase bone mass[J]. Nat Med，2012，18（3）：456-462. DOI：10.1038/nm.2665.
[30]	Wei Y, Jiang S, Si M，et al. Chirality Controls Mesenchymal Stem Cell Lineage Diversification through Mechanoresponses[J]. Adv Mater，2019，31（16）：e1900582. DOI：10.1002/adma.201900582.
[31]	Zhu J, Cai Q, Zhang X，et al. Biological characteristics of mesenchymal stem cells grown on different topographical nanofibrous poly-L-lactide meshes[J]. J Biomed Nanotechnol，2013，9（10）：1757-1767. DOI：10.1166/jbn.2013.1661.
[32]	Raines AL, Berger MB, Schwartz Z，et al. Osteoblasts grown on microroughened titanium surfaces regulate angiogenic growth factor production through specific integrin receptors[J]. Acta Biomater，2019，97：578-586. DOI：10.1016/j.actbio.2019.07.036.
[33]	Chen Q, Shou P, Zhang L，et al. An osteopontin-integrin interaction plays a critical role in directing adipogenesis and osteogenesis by mesenchymal stem cells[J]. Stem cells，2014，32（2）：327-337. DOI：10.1002/stem.1567.
[34]	Hartman GD, Duggan ME. α_vβ₃ Integrin antagonists as inhibitors of bone resorption[J]. Expert Opin Investig Drugs，2000，9（6）：1281-1291. DOI：10.1517/13543784.9.6.1281.
[35]	Wang Y, Guo Q, Hei H，et al. BK ablation attenuates osteoblast bone formation via integrin pathway[J]. Cell Death Dis，2019，10（10）：738. DOI：10.1038/s41419-019-1972-8.
[36]	Globus RK, Amblard D, Nishimura Y，et al. Skeletal phenotype of growing transgenic mice that express a function-perturbing form of beta1 integrin in osteoblasts[J]. Calcif Tissue Int，2005，76（1）：39-49. DOI：10.1007/s00223-004-0309-4.
[37]	Brunner M, Millon-Frémillon A, Chevalier G，et al. Osteoblast mineralization requires beta1 integrin/ICAP-1-dependent fibronectin deposition[J]. J Cell Biol，2011，194（2）：307-322. DOI：10.1083/jcb.201007108.
[38]	Qin L, Liu W, Cao H，et al. Molecular mechanosensors in osteocytes[J]. Bone Res，2020，8：23. DOI：10.1038/s41413-020-0099-y.
[39]	Cora-Cruz JJ, Diffoot-Carlo N, Sundaram PA. Vinculin expression in MC3T3-E1 cells in response to mechanical stimulus[J]. Data Brief，2016，6：94-100. DOI：10.1016/j.dib.2015.11.052.
[40]	Zhang K, Barragan-Adjemian C, Ye L，et al. E11/gp38 selective expression in osteocytes：regulation by mechanical strain and role in dendrite elongation[J]. Mol Cell Biol，2006，26（12）：4539-4552. DOI：10.1128/mcb.02120-05.
[41]	Nobuta H, Katagi M, Kume S，et al. A role for bone marrow-derived cells in diabetic nephropathy[J]. FASEB J，2019，33（3）：4067-4076. DOI：10.1096/fj.201801825R.
[42]	Brunner M, Jurdic P, Tuckerman JP，et al. New insights into adhesion signaling in bone formation[J]. Int Rev Cell Mol Biol，2013，305：1-68. DOI：10.1016/B978-0-12-407695-2.00001-9.

整联蛋白亚基	配体	表达细胞	功能作用	相关信号通路
α1	Ⅰ型胶原蛋白	间充质干细胞	间充质干细胞增殖	BMP
	Ⅳ型胶原蛋白	成骨细胞	成骨向分化	EGFR
	层黏连蛋白	骨细胞
α2	Ⅰ型胶原蛋白	间充质干细胞	细胞黏附、增殖、迁移、成骨向分化、骨吸收	BMP
	Ⅱ型胶原蛋白	成骨细胞		FAK
	层黏连蛋白	骨细胞		PI3K-AKT
		破骨细胞		MAPK
α4	纤连蛋白	骨髓来源间充质干细胞	骨髓来源间充质干细胞归巢	PI3K-AKT
		成骨细胞	成骨向分化
α5	纤连蛋白	间充质干细胞	细胞黏附、增殖、迁移、成骨向分化、机械传导	BMP
		成骨细胞		FAK
		骨细胞		PI3K-AKT
				MAPK
αV	玻连蛋白	间充质干细胞	成骨向分化	MAPK
		成骨细胞	骨吸收	RANKL
		破骨细胞
β1	α1~α11	间充质干细胞	细胞黏附、增殖、成骨向分化、机械传导、细胞外基质沉积	FAK
	αⅤ	成骨细胞		ERK
		骨细胞
		破骨细胞
β3	αⅡ	骨细胞	机械传导	FAK
	αV	破骨细胞		PI3K-AKT

整联蛋白亚基	配体	表达细胞	功能作用	相关信号通路
α1	Ⅰ型胶原蛋白	间充质干细胞	间充质干细胞增殖	BMP
	Ⅳ型胶原蛋白	成骨细胞	成骨向分化	EGFR
	层黏连蛋白	骨细胞
α2	Ⅰ型胶原蛋白	间充质干细胞	细胞黏附、增殖、迁移、成骨向分化、骨吸收	BMP
	Ⅱ型胶原蛋白	成骨细胞		FAK
	层黏连蛋白	骨细胞		PI3K-AKT
		破骨细胞		MAPK
α4	纤连蛋白	骨髓来源间充质干细胞	骨髓来源间充质干细胞归巢	PI3K-AKT
		成骨细胞	成骨向分化
α5	纤连蛋白	间充质干细胞	细胞黏附、增殖、迁移、成骨向分化、机械传导	BMP
		成骨细胞		FAK
		骨细胞		PI3K-AKT
				MAPK
αV	玻连蛋白	间充质干细胞	成骨向分化	MAPK
		成骨细胞	骨吸收	RANKL
		破骨细胞
β1	α1~α11	间充质干细胞	细胞黏附、增殖、成骨向分化、机械传导、细胞外基质沉积	FAK
	αⅤ	成骨细胞		ERK
		骨细胞
		破骨细胞
β3	αⅡ	骨细胞	机械传导	FAK
	αV	破骨细胞		PI3K-AKT

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