张永;魏鹤翔;张腾;吴定;张成俊;

• 1:兰州大学第二临床医学院
• 2:兰州大学第二医院骨科

摘要(Abstract)：

成骨细胞是骨组织中重要的的刺激感受细胞和效应细胞,参与多种力学刺激下骨的修复及重建。流体剪切应力是人体内骨组织受到的最直接的力学刺激,已有大量研究证明流体剪切应力可以通过激活Wnt信号通路、BMP-Smad依赖性信号通路或BMP-非Smad依赖性信号通路促进成骨细胞增殖分化。近年来,越来越多的研究发现流体剪切应力还可以通过激活ERK5信号通路、PI3K/AKT激酶信号通路等途径抑制成骨细胞凋亡,这为流体剪切应力促进成骨细胞增殖提供了一个新的研究方向。本文就近年来流体剪切应力促进成骨细胞增殖的影响机制作一综述,希望能为骨科相关疾病的防治及研究提供参考。

关键词(KeyWords)： 成骨细胞;流体剪切应力;凋亡抑制;信号通路

Abstract:

Keywords:

基金项目(Foundation): 兰州市科技发展计划项目《骨细胞生物力学工程靶点下增殖/凋亡功效性研究》(编号：2016-3-121);; 兰州大学第二医院“萃英学子科研培育”计划项目(编号：CYXZ2019-03)

作者(Author): 张永;魏鹤翔;张腾;吴定;张成俊;

Email:

DOI:

参考文献(References)：

• [1] Katsimbri, P. The biology of normal boneremodeling[J]. Eur J Cancer Care, 2017, 2017:12740.
• [2] Robling AG, Castillo AB, Turner CH. Biomechanical and molecular regulation of bone remodeling[J]. Ann Rev of Biomed Engin,2006, 8(1):455-498.
• [3] Plotkin LI, Bellido T. Osteocytic signalling pathways as therapeutic targets for bone fragility[J]. Nat Rev Endocrinol, 2016, 41(2):791-795.
• [4] Prisby RD. Mechanical, hormonal and metabolic influences on blood vessels, blood flow and bone[J]. J Endocrinol, 2017, 235(3):JOE-16-0666.
• [5] Aisha MD, NorAshikin MNK, Sharaniza ABR, et al. Orbitalfluid shear stress promotes osteoblast metabolism, proliferationandalkaline phosphates activity in vitro[J]. Expe Cell Research, 2015:S0014482715300331.
• [6] Li P, Ma Y, Sheng X, et al. Cyclic fluid shear stress promotes osteoblastic cells proliferation through ERK5 signaling pathway[J]. Molecular Cell Bioc, 2012, 364(41641):321-327.
• [7] Letechipia JE, Alessi A, Rodriguez G, et al. Would increased interstitial fluid flow through in situ mechanical stimulation enhance bone remodeling[J]. Med Hypoth, 2010, 75(2):196-198.
• [8] Frost HM. A 2003 update of bone physiology and Wolff's Law for clinicians[J]. Ang Orthodontist, 2004, 74(1):3.
• [9] The Classic. On the inner architecture of bones and its importance for bone growth[J]. Clin Orthop, 2010, 468(4):1056-1065.
• [10] Sharma RP, Chopra VL. Effect of the wingless(wg1)mutation on wing and haltere development in drosophila melanogaster[J]. Dev Biol, 1976, 48(2):461-465.
• [11] Nusslein-Volhard C. Mutation affecting segment number and polarity in drosophila[J]. Nature, 1980, 287(5785):795-801.
• [12] Duan P, Bonewald LF. The role of the wnt/β-catenin signaling pathway in formation and maintenance of bone and teeth[J]. Int J Biochemistry Cell Biol, 2016:S1357272516301212.
• [13] Tang WR, Liu Y, Li LH, et al. Fluid shear stress and raloxifene stimulates the proliferation of osteoblast through regulating the expresstion ofβ-catenin and estrogen receptorα[J]. J Sichuan University, 2014, 45(6):913.
• [14] Zedong Y, Pan W, Junjie W, et al. Fluid shear stress improves morphology, cytoskeleton architecture, viability and regulates cytokine expression in a time-dependent manner in MLO-Y4 cells[J]. Cell Biol Int, 2018, 9(2):457-462.
• [15] Jaswinder K. Sethi, Vidalpuig A. Wnt signalling and the control of cellular metabolism[J]. Biochem J, 2010, 427(1):1-17.
• [16] Yao Q, Yu C, Zhang X, et al. Wnt/β-catenin signaling in osteoblasts regulates global energy metabolism[J]. Bone, 2017, 97:175-183.
• [17] Ii DAG, Bialek P, Ahn JD, et al. Canonical wnt signaling in differentiated osteoblasts controls osteoclast differentiation[J]. Developmental Cell, 2005, 8(5):764.
• [18] Salazar VS, Gamer LW, Rosen V. BMP signalling in skeletal development, disease and repair[J]. Nat Rev Endocrinol, 2016, 41(2):801-809.
• [19] Wozney J, Rosen V, Celeste A, et al. Novel regulators of bone formation:molecular clones and activities[J]. Science, 1988, 242
• [20](D4a8n8i5è)l e:1N5o2?8l,-1G5a3zi4t. D, Bouquet C, et al. Short-term BMP-2 expression is sufficient for in vivo osteochondral differentiation of mesenchymal stem cells[J]. Stem Cells(Miamisburg), 2004, 22(1):74-85.
• [21] Shen B, Wei A, Whittaker S, et al. The role of BMP-7 in chondrogenic and osteogenic differentiation of human bone marrow multipotent mesenchymal stromal cells in vitro[J]. J Cellular Biochemistry, 2010, 109(2):253-257.
• [22] Wu M, Chen G, Li YP. TGF-βand BMP signaling in osteoblast,skeletal development, and bone formation, homeostasis and disease[J]. Bone Research, 2016, 4:16009.
• [23] Karner CM, Lee SY, Long F. Bmp induces osteoblast differentiation through both smad4 and mTORC1 signaling[J]. Molecular Cell Biol, 2017, 37(4):253-256.
• [24] Kido S, Kuriwaka-Kido R, Umino-Miyatani Y, et al. Mechanical stress activates smad pathway through PKCδto enhance interleukin-11 gene transcription in osteoblasts[J]. Plos One, 2010, 5:1-10.
• [25] Komori T. Roles of runx2 in skeletal development[J]. Oxygen Transport Tissue, 2017, 962(1):83-93.
• [26] Rahman MS, Akhtar N, Jamil HM, et al. TGF-β/BMP signaling and other molecular events:regulation of osteoblastogenesis and bone formation[J]. Bone Research, 2015, 3(1):11-30.
• [27] Li Y, Ge C, Long J P, et al. Biomechanical stimulation of osteoblast gene expression requires phosphorylation of the RUNX2 transcription factor[J]. J Bone Mine, 2012, 27(6):10-19.
• [28] Norberg E, Orrenius S, Zhivotovsky B. Mitochondrial regulation of cell death:processing of apoptosis-inducing factor(AIF)[J]. Biochem Biophysical Res Commun, 2010, 396(1):91-100.
• [29] Ling-Ling H, Yun WU, Bin W, et al. Mechanism study of simvastatin inhibiting the apoptosis of alveolar osteoblasts by regulating activation of transforming growth factor-beta 1/Smad 3 pathway[J]. Chin J Clin Pharmacol, 2019, 24(41):148-152.
• [30] De Luca V, Roehrborn CG, Pescatori ES, et al. Differential effects of ERK and p38 signaling in BMP-2 stimulated hypertrophy of cultured chick sternal chondrocytes[J]. Cell Communication Signaling Ccs, 2005, 3(1):3.
• [31] Zhao L, Chen S, Teng Y, et al. The MEK5/ERK5 pathway mediates fluid shear stress promoted osteoblast differentiation[J]. Connective Tissue Res, 2014, 55(2):96-102.
• [32] Ding N, Geng B, Li Z, et al. Fluid shear stress promotes osteoblast proliferation through the NFATc1-ERK5 pathway[J]. Connective Tissue Res, 2018:03008207.
• [33] Adam C, Lucia G, Ebert R, et al. The MEK5/ERK5 mitogen-activated protein kinase cascade is an effector pathway of bone-sustaining bisphosphonates that regulates osteogenic differentiation and mineralization[J]. Bone, 2018, 111(1):49-58.
• [34] Zhang B, Geng B, Wang J, et al. Fluid shear stress promotes osteoblast proliferation via the galpha q-ERK5 signaling pathway[J].Connective Tissue Research, 2016, 57(4):299-306.
• [35] Pavalko FM, Gerard RL, Ponik SM, et al. Fluid shear stress inhibits TNF-αinduced apoptosis in osteoblasts:a role for fluid shear stress-induced activation of PI3-kinase and inhibition of caspase-3[J]. J Cell Physiol, 2003, 194(2):194-205.
• [36] Geng B, Zhang B, Wang J, et al. Fluid shear stress suppresses TNF-alpha-induced apoptosis in MC3T3-E1 cells:involvement of ERK5-AKT-FoxO3a-Bim/FasL signaling pathways[J]. Exper Cell Res, 2016, 343(2):208-217.
• [37] Fluid shear stress inhibits TNF-α-induced osteoblast apoptosis via ERK5 signaling pathway[J]. Biochem Biophysical Res Commun, 2015, 466(1):117-123.
• [38] Xia G, Li X, Yin X, et al. Mangiferin protects osteoblast against oxidative damage by modulation of ERK5/Nrf2 signaling[J]. Biochem Biophysical Res Commun, 2017:S0006291X17313153.
• [39] Li X, Liu C, Li P, et al. Connexin 43 is a potential regulator in fluid shearstress-inducedsignaltransduction in osteocytes[J]. J Orthop Res, 2013, 31(12):1959-1965.
• [40] Yu L, Wang X, Gao X, et al. The calcium transient characteristics induced by fluid shear stress affect the osteoblast proliferation[J].Exper Cell Res, 2017:S0014482717305864.