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CHEN Xianghe, PENG Haixia, SUN Peng, LI Shichang. Effect of Different Mechanical Stimulation on the TGF-β/Smad Pathway and Bone Formation in Type 2 Diabetes Mellitic Mice[J]. Journal of Shanghai University of Sport, 2018, 42(3): 95-102. DOI: 10.16099/j.sus.2018.03.016
Citation: CHEN Xianghe, PENG Haixia, SUN Peng, LI Shichang. Effect of Different Mechanical Stimulation on the TGF-β/Smad Pathway and Bone Formation in Type 2 Diabetes Mellitic Mice[J]. Journal of Shanghai University of Sport, 2018, 42(3): 95-102. DOI: 10.16099/j.sus.2018.03.016

Effect of Different Mechanical Stimulation on the TGF-β/Smad Pathway and Bone Formation in Type 2 Diabetes Mellitic Mice

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  • Received Date: May 24, 2017
  • Revised Date: August 02, 2017
  • Publish Date: May 29, 2018
  • Issue Publish Date: May 29, 2018
  •   Objective  to explore the effect of different mechanical stimulation on TGF-β/Smad pathway and bone formation in type 2 diabetes mellitic mice.
      Method  T2DM mice, built by high-fat diet and injection STZ, were randomly divided into T2DM control group (T2DM), T2DM swimming group (TS) and T2DM downhill group (TD), and also normal control group.The mice of TS and TD group were respectively treated with 8 weeks of swimming and downhill running.RT-PCR was used to detect the mRNA expression of related factors in the right femur.Western-blotting was used to detect the expression of related factor proteins in the right tibia.BMSCs were cultured and induced to differentiate into OB.Alizarin Red staining was used to stain OB.The skull was stained with Alizarin Red dye.Left femur BMD was detected by Micro-CT.The wet weight and bone shape of right femur were detected by electronic scale and vernier caliper.
      Results  Compared with ZC group, the mRNA expression of TGF-β, Smad2, Smad3, Smad4, Runx2 and Osx and the protein expression of p-Smad2, p-Smad3 and Smad4 in TC group were significantly decreased (P < 0.05 or P < 0.01).The bone formation capacity of OB and skull, bone mineral density of trabecular and cortical and also the morphological size of femur were significantly decreased.Compared with TC group, the mRNA expression of TGF-β, Osx and the protein expression of p-Smad2 and p-Smad3 were significantly up-regulated in TS group (P < 0.05 or P < 0.01).The osteoblastic ability of OB and skull was significantly increased (P < 0.05 or P < 0.01);the wet weight of femur was improved (P < 0.01).The mRNA expression of TGF-β, Smad2, Runx2 and Osx and protein expression of p-Smad2, p-Smad3 and Smad4 were significantly up-regulated in TD group (P < 0.05 or P < 0.01).The osteoblastic capacity of OB and skull, BMD of trabecular, wet weight of the femur, the width of the distal coronal axis of the femur and the sagittal axis of the distal femur were significantly increased (P < 0.01).Compared with TS group, the mRNA expression of Smad2 and Osx and protein expression of p-Smad2, p-Smad3 and Smad4 of TD group were improved (P < 0.05).The osteoblastic ability of OB and skull was enhanced and the width of sagittal axis of femur was significantly increased (P < 0.05).
      Conclusion  Bone formation in T2DM mice was inhibited.The direct effect of downhill running on bone formation in T2DM mice was improved by activating TGF-β/Smad pathway, promoting bone formation, increasing BMD, and improving bone wet weight and shape, and its effect was superior to the indirect force generated by swimming.
  • [1]
    OLIVEIRA J M, REBUFFAT S A, GASA R, et al.Targeting type 2 diabetes:Lessons from a knockout model of insulin receptor substrate 2[J].Canadian Journal of Physiology & Pharmacology, 2014, 92(8):613-620 http://cn.bing.com/academic/profile?id=104cdaacca79fca9d4b878a117c4c7e3&encoded=0&v=paper_preview&mkt=zh-cn
    [2]
    黄冬梅, 陆付耳.胰岛素信号转导障碍与胰岛素抵抗的形成[J].生理科学进展, 2003, 34(3):212-216 http://www.cqvip.com/QK/90119X/200303/8529133.html
    [3]
    FREUDE T, BRAUN K F, HAUG A, et al.Hyperinsulinemia reduces osteoblast activity in vitro via upregulation of TGF-β[J].Journal of Molecular Medicine, 2012, 90(11):1257-1266 doi: 10.1007/s00109-012-0948-2
    [4]
    陈祥和, 李世昌, 严伟良, 等.不同方式运动对生长期雄性小鼠骨形成和骨吸收代谢影响的研究[J].西安体育学院学报, 2015, 32(2):205-211 http://www.cnki.com.cn/Article/CJFDTotal-XATY201502015.htm
    [5]
    GUSHIKEN M, KOMIYA I, UEDA S, et al.Heel bone strength is related to lifestyle factors in Okinawan men with type 2 diabetes mellitus[J].Journal of Diabetes Investigation, 2015, 6(2):150-157 doi: 10.1111/jdi.2015.6.issue-2
    [6]
    BELLO M, SOUSA M C, NETO G, et al.The effect of a long-term, community-based exercise program on bone mineral density in post-menopausal women with pre-diabetes and type 2 diabetes[J].Journal of Human Kinetics, 2014, 43(13):43-48 http://cn.bing.com/academic/profile?id=b5eddaf0ffd728a2bf1f9888c34c78e8&encoded=0&v=paper_preview&mkt=zh-cn
    [7]
    赵剑. 有氧运动对2型糖尿病大鼠骨密度和骨生物力学指标的影响[D]. 上海: 上海体育学院, 2010: 15
    [8]
    KANAZAWA I, YAMAGUCHI T, YAMAUCHI M, et al.Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus[J].Osteoporosis International, 2011, 22(1):187-194 doi: 10.1007/s00198-010-1184-7
    [9]
    ARYAL A C S, MIYAI K, IZU Y, et al.Nck influences preosteoblastic/osteoblastic migration and bone mass[J].Proceedings of the National Academy of Sciences of the United States of America, 2015, 112(50):15432-15437 doi: 10.1073/pnas.1518253112
    [10]
    SHI Y, MASSAGUE J.Mechanisms of TGF-beta signaling from cell membrane to the nucleus[J].Cell, 2003, 113(6):685-700 doi: 10.1016/S0092-8674(03)00432-X
    [11]
    YASUI T, KADONO Y, NAKAMURA M, et al.Regulation of RANKL-induced osteoclastogenesis by TGF-beta through molecular interaction between Smad3 and Traf6[J].Journal of Bone & Mineral Research, 2011, 26(7):1447-1456 http://cn.bing.com/academic/profile?id=7ec13ed5abdb7f7f7b3da22b3d78331a&encoded=0&v=paper_preview&mkt=zh-cn
    [12]
    GHIRALDINI B, CONTE A, CASARIN RC, et al.Influence of glycemic controlon perimplant bone healing:12-month outcomes of local release of bone-related factors and implant stabilization in type 2 diabetics[J].Clinical Implant Dentistry & Related Research, 2016, 18(4):801-809
    [13]
    EHNERT S, FREUDE T, IHLE C, et al.Factors circulating in the blood of type 2 diabetes mellitus patients affect osteoblast maturation-description of a novel in vitro model[J].Experimental Cell Research, 2015, 332(2):247-258 doi: 10.1016/j.yexcr.2014.12.011
    [14]
    PACIOS S, KANG J, GALICIA J, et al.Diabetes aggravates periodontitis by limiting repair through enhanced inflammation[J].FASEB Journal, 2012, 26(4):1423-1430 doi: 10.1096/fj.11-196279
    [15]
    CASELLI A, OLSON TS, OTSURU S, et al.IGF-1-mediated osteoblastic niche expansion enhances long-term hematopoietic stem cell engraftment after murine bone marrow transplantation[J].Stem Cells, 2013, 31(10):2193-2204 doi: 10.1002/stem.1463
    [16]
    宋会平. 血液成分与骨组织的内在联系及组织工程学评价[D]. 广州: 南方医科大学, 2008: 36
    [17]
    YANG T, GRAFE I, BAE Y, et al.E-selectin ligand 1 regulates bone remodeling by limiting bioactive TGF-β in the bone microenvironment[J].Proceedings of the National Academy of Sciences of the United States of America, 2013, 110(18):7336-7341 doi: 10.1073/pnas.1219748110
    [18]
    SHEN K, KENG YF, WU L, et al.Acquisition of a specific and potent PTP1B inhibitor from a novel combinatorial library and screening procedure[J].Journal of Biological Chemistry, 2001, 276(50):47311-47319 doi: 10.1074/jbc.M106568200
    [19]
    李文龙, 王晨辉, 魏传宇, 等.MKP2和MKP3抑制TGF-beta/Smad转录活性[J].科学技术与工程, 2010, 10(13):1671-1674 http://mall.cnki.net/magazine/Article/KXJS201013007.htm
    [20]
    LAVERY C A, KUROWSKA-STOLARSKA M, HOLMES W M, et al.MiR-34a-/- mice are susceptible to diet-induced obesity[J].Obesity, 2016, 24(8):1741-1751 doi: 10.1002/oby.21561
    [21]
    WANG J M, TAO J, CHEN D D, et al.MicroRNA miR-27b rescues bone marrow-derived angiogenic cell function and accelerates wound healing in type 2 diabetes Mellitus[J].Arteriosclerosis, Thrombosis, and Vascular Biology, 2014, 34(1):99-109 doi: 10.1161/ATVBAHA.113.302104
    [22]
    YOU L, PAN L, CHEN L, et al.MiR-27a is essential for the shift from osteogenic differentiation to adipogenic differentiation of mesenchymal stem cells in postmenopausal osteoporosis[J].Cellular Physiology and Biochemistry, 2016, 39(1):253-265 doi: 10.1159/000445621
    [23]
    PARK J S, BAE S J, CHOI S W, et al.A novel 11beta-HSD1 inhibitor improves diabesity and osteoblast differentiation[J].Journal of Molecular Endocrinology, 2014, 52(2):191-202 doi: 10.1530/JME-13-0177
    [24]
    徐飞, 董永辉, 黄鑫, 等.2型糖尿病对小鼠骨代谢的影响[J].中国骨质疏松杂志, 2014, 20(3):238-241 http://mall.cnki.net/magazine/Article/YXZS200405013.htm
    [25]
    ZHANG M, SARA J D, WANG F L, et al.Increased plasma BMP-2 levels are associated with atherosclerosis burden and coronary calcification in type 2 diabetic patients[J].Cardiovascular Diabetology, 2015, 14(7):59-64 http://cn.bing.com/academic/profile?id=eb5eeb63a9034576a3b24e2dd650d568&encoded=0&v=paper_preview&mkt=zh-cn
    [26]
    YOUN J Y, ZHOU J, CAI H.Bone morphogenic protein 4 mediates NOX1-dependent eNOS uncoupling, endothelial dysfunction, and COX2 induction in type 2 diabetes mellitus[J].Molecular Endocrinology, 2015, 29(8):1123-1133 doi: 10.1210/ME.2014-1313
    [27]
    YU N, ZHANG Y Y, NIU X Y, et al.Evaluation of shear wave velocity and human bone morphogenetic protein-7 for the diagnosis of diabetic kidney disease[J].PLoS One, 2015, 10(3):e119713 http://cn.bing.com/academic/profile?id=75ced3f0a1e594931a5b7529220a3acc&encoded=0&v=paper_preview&mkt=zh-cn
    [28]
    OHATA Y, OZONO K.Bone and stem cells.The mechanism of osteogenic differentiation from mesenchymal stem cell[J].Clinical Calcium, 2014, 24(4):501-508
    [29]
    曾伟光, 邝建, 陈亮, 等.2型糖尿病成骨细胞功能与血清IGFs水平的关系[J].广东医学, 2001, 22(12):1131-1132 doi: 10.3969/j.issn.1001-9448.2001.12.020
    [30]
    FU C, ZHANG X, YE F, et al.High insulin levels in KK-Ay diabetic mice cause increased cortical bone mass and impaired trabecular micro-structure[J].International Journal of Molecular Sciences, 2015, 16(4):8213-8226 http://cn.bing.com/academic/profile?id=01b414f650bc4e53a76dbb99d56479f9&encoded=0&v=paper_preview&mkt=zh-cn
    [31]
    LI J, ZHANG Y, ZHAO Q, et al.MicroRNA-10a influences osteoblast differentiation and angiogenesis by regulating beta-catenin expression[J].Cell Physiology & Biochemistry, 2015, 37(6):2194-2208 http://cn.bing.com/academic/profile?id=1b6decd9b1bd62e1a9319281666b2256&encoded=0&v=paper_preview&mkt=zh-cn
    [32]
    DONG X, BI L, HE S, et al.FFAs-ROS-ERK/P38 pathway plays a key role in adipocyte lipotoxicity on osteoblasts in co-culture[J].Biochimie, 2014, 101(12):123-131 http://cn.bing.com/academic/profile?id=86a4dc5e3d88bac10219c5fbf8e911cb&encoded=0&v=paper_preview&mkt=zh-cn
    [33]
    LI J, HE W, LIAO B, et al.FFA-ROS-P53-mediated mitochondrial apoptosis contributes to reduction of osteoblastogenesis and bone mass in type 2 diabetes mellitus[J].Scientific Reports, 2015, 31(5):127-135 http://cn.bing.com/academic/profile?id=3abc66c57faa9d33c635b72560748e47&encoded=0&v=paper_preview&mkt=zh-cn
    [34]
    YAMAGUCHI T.Bone fragility in type 2 diabetes mellitus[J].World Journal of Orthopedics, 2010, 1(1):3-9 doi: 10.5312/wjo.v1.i1.3
    [35]
    SHARP L A, LEE Y W, GOLDSTEIN A S.Effect of low-frequency pulsatile flow on expression of osteoblastic genes by bone marrow stromal cells[J].Annals of Biomedical Engineering, 2009, 37(3):445-453 doi: 10.1007/s10439-008-9632-7
    [36]
    THONGCHOTE K, SVASTI S, TEERAPORNPUNTAKIT J, et al.Running exercise alleviates trabecular bone loss and osteopenia in hemizygous beta-globin knockout thalassemic mice[J].American Journal of Physiology Endocrinology & Metabolism, 2014, 306(12):1406-1417 https://www.researchgate.net/publication/262000837_Running_exercise_alleviates_trabecular_bone_loss_and_osteopenia_in_hemizygous_-globin_knockout_thalassemic_mice
    [37]
    FRAJACOMO F T, FALCAI M J, FERNANDES C R, et al.Biomechanical adaptations of mice cortical bone submitted to three different exercise modalities[J].Acta Ortopedica Brasileira, 2013, 21(6):328-332 doi: 10.1590/S1413-78522013000600006
    [38]
    LANDIM B T, BRITO V G, do AMARAL C C, et al.Osteogenic markers are reduced in bone-marrow mesenchymal and femoral bone of young spontaneously hypertensive rats[J].Life Sciences, 2016, 146(12):174-183 http://cn.bing.com/academic/profile?id=d76ea12c6dff449ff2b421feb1f15ba8&encoded=0&v=paper_preview&mkt=zh-cn
    [39]
    陈祥和, 李世昌, 孙朋, 等.下坡跑对生长期去卵巢小鼠骨BMP-2、Smad1/5和Runx2表达的影响[J].中国运动医学杂志, 2013, 32(7):609-614. http://cdmd.cnki.com.cn/Article/CDMD-10269-2009187235.htm
    [40]
    LI H, JIANG L S, DAI L Y.High glucose potentiates collagen synthesis and bone morphogenetic protein-2-induced early osteoblast gene expression in rat spinal ligament cells[J].Endocrinology, 2010, 151(1):63-74 doi: 10.1210/en.2009-0833
    [41]
    杨念恩. 不同方式运动对生长期小鼠骨合成代谢和Wnt信号通路的影响[D]. 上海: 华东师范大学, 2014: 25
    [42]
    陈祥和, 李世昌, 孙朋, 等.下坡跑对生长期雌性去卵巢小鼠成骨细胞分化和骨形成的影响[J].中国运动医学杂志, 2014, 33(2):130-134 http://www.cnki.com.cn/Article/CJFDTotal-YDYX201402007.htm
    [43]
    NAKAI M, COOK L, PYTER LM, et al.Dietary soy protein and isoflavones have no significant effect on bone and a potentially negative effect on the uterus of sexually mature intact Sprague-Dawley female rats[J].Menopause, 2005, 12(3):291-298 doi: 10.1097/01.GME.0000146109.50235.DO
    [44]
    CAMERINO C, ZAYFOON M, RYMASZEWSKI M, et al.Central depletion of brain-derived neurotrophic factor in mice results in high bone mass and metabolic phenotype[J].Endocrinology, 2012, 153(11):5394-5405 doi: 10.1210/en.2012-1378
    [45]
    BURKEMPER K M, GARRIS D R.Influences of obese (ob/ob) and diabetes (db/db)genotype mutations on lumber vertebral radiological and morphometric indices:Skeletal deformation associated with dysregulated systemic glucometabolism[J].BMC Musculoskeletal Disorders, 2006, 7(5):10-16 doi: 10.1186/1743-0003-7-3
    [46]
    HAFEZ A, SQUIRES R, PEDRACINI A, et al.Col1α1 regulates bone microarchitecture during embryonic development[J].Journal of Developmental Biology, 2015, 3(4):158-176. doi: 10.3390/jdb3040158
    [47]
    RUBIN M R.Bone cells and bone turnover in diabetes mellitus[J].Current Osteoporosis Reports, 2015, 13(3):186-191 doi: 10.1007/s11914-015-0265-0
    [48]
    吴学伦. 2型糖尿病患者血清Sclerostin和Dkk1水平与骨密度相关性研究[D]. 石家庄: 河北医科大学, 2014: 65
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