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《体育科学》2020年(第40卷)第4期 3结论与展望 NFATcl expression determines its essential role in bone homeostasis 直以来,相关研究都在从力学刺激下的骨相关因]. J Exp Med,202(9):1261-1269 子、激素、信号通路变化等方面论证适量运动有益于维持 BACKES0cM,uY, LINDGREN U,ea,2000 Activation of 骨稳态,并大力推广运动科学健骨的理念,而表观遗传正 SirtI decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells[ J]. J Bone Miner Res, 21(7):993-1002 为运动这一外源性刺激引起的骨相关基因响应内外环境BNZ, JUNFENG Z,JAOL,etal,2015 microRNA0 Sa functions 变化,并呈现出时间和空间上的表达调控改变,提供了最 as a mechanosensitive microrna to inhibit bone formation through 新探究角度。近年来,相关研究为骨健康和运动医学领 targeting runx2[ J]. J Bone Miner Res,30(2):330-345 域积累了一定的表观遗传学资料,通过影响基因的表观 BRYAN A D, MAGNAN R E, HOOPER A E, et al. 2013, Physical 遗传修饰,影响骨相关基因的表达,可能是运动改善骨质 activity and differential methylation of breast cancer genes assayed from saliva: A preliminary investigation [J]. Ann Behav Med, 45 的良性机制之一。尽管将表观遗传修饰、运动和骨质代 (1):89-98 谢直接联系起来的研究并不多见,但通过对文献的整理 CANTLEY M D. ZANNETTINO A. BARTOLD P M. et al. 2017 可以看出,运动能显著改变DNA甲基化水平、组蛋白修饰 stone deacetylases(HDAc) in physiological and pathological 状态及非编码RNA的表达,当中的部分表观遗传修饰变 bone remodelling[j].Bone,95:162-174 化与骨质代谢标志物、信号通路和关键基因的表达密切 CHENG VK. AU PC, TAN K C. et al. 2018. microRNA and human bone Health[J]. JBMR Plus, 3(1): 2-13 相关。然而,关于表观遗传的诸多疑问仍未解决,如机体 COHENKFIR E,ARTS1H, LEVIN A,etal,.201 SirtI is a 表型与代谢性疾病的发生由基因遗传和表观遗传共同决 regulator of bone mass and a repressor of Sost encoding for 定,应如何区分和量化两者影响程度的多寡;不同运动项 sclerostin, a bone formation inhibitor[. Endocrinol.152(12) 目、时长、强度和频次与骨相关表观遗传修饰变化之间的 4514-4524. 关联等有待长期实验进行验证。同时,运动对干细胞表 DENHAM J. OBRIEN B J. HARVEY JT. et al. 2015 Genome- wide sperm DNA methylation changes after 3 months of exercise 观遗传修饰的影响或将成为运动医学领域的新兴课题。 training in humans[J]. Epigenomics, 7(5):717-731 未来还可将慢性骨代谢疾病与生活环境、生活方式等表 DOMANSKA- SENDEROWSKA D, LAGUETTE MN, JEGIER A 观遗传修饰的决定因素相联系,从诱因入手以减少骨疾 et al., 2019. microRNA profile and adaptive response to exercise 病发生的可能。 training:A review[J]. Int J Sports Med, 40(4): 227-235 EHLERT T. SIMON P. MOSER D A 2013. Epigenetics in sports[J] ports Med. 43(2): 93-110 参考文献 FARSANI Z H. BANITABLEBI E. FARAMARZI M. et al. 2019 曹鹏,2009.不同强度跑台运动对老龄雌性大鼠骨量及骨代谢的影 Effects of different intensities of strength and endurance training on 响[J]北京体育大学学报,32(2):74-76 some osteometabolic miRNAs, Runx2 and PPARy in bone marrow 马涛,李世昌,梁晓霞,等,2011.上、下坡跑台运动对去卵巢小鼠骨 of old male wistar rats[ J]. Mol Biol Rep, 46(2):2513-2521 密度及骨组织形态计量学指标的影响[J体育科学,311): FERRARA N, RINALDI B, CORBI G,etal,2008. Exercise training 48-5. promotes SIRTI activity in aged rats[J]. Rejuvenati Res, 11(1) 王维,孟智启,石放雄,2012.组蛋白修饰及其生物学效应[]遗传 139-150 GAVIN KM. KOHRT WM. KLEMM DJ, et al. 2018 Modulation 杨宜锜,汤亭亭,2019.SIRT1信号通路对于骨代谢的调节作用[] of energy expenditure by estrogens and exercise in women [J] 上海交通大学学报(医学版)39(11):1335-1340 Exerc Sport Sci Rev. 46(4): 232-239. 张奎刘洋,马煜,等,2017.骨质疏松性骨折与相关基因多态性研究 GORDON JA, HASSAN M O, KOSS M,etal.,201l. Epigenetic 进展[J中国骨质疏松杂志23(7):974980 张严焱,徐召霞,陈渝,等,2018.运动改善高血压肠系膜动脉LTCC a HOXA10-PBXI-associated complex[J]. Cells Tissues Organs, 194 和BKCa通道功能的表观遗传调控机制[J.体育科学,38(11) (2-4):146-150 39-49 GRUNSTE 1997 Histone acetylation in chromatin structure and BLOOMFIELD SA,2003营养、运动和激素促进骨健康的作用[]. transcription[J].Nature,389(669):349-352 体育科学,23(1):133-137 HE L. van Roie E BOGAErts A. et al.. 2018. Genetic AMJADI-MOHEB F. AKHAVAN-NIAKI H. 2019. Wnt signaling predisposition score predicts the increases of knee strength pathway in osteoporosis: Epigenetic regulation, interaction with muscle mass after one-year exercise in healthy elderly [J]. Exp other signaling pathways, and therapeutic promises [J].CEll hysiol. 15(1): 1 JAGER S. HANDSCHIN C. ST-PIERRE J. et al.. 2007. AMP. ANDREOLI A. CELI M, VOLPE S L. et al. 2012. Long-term effect activated protein kinase(AMPK) action in skeletal muscle via of exercise on bone mineral density and body composition in post- direct phosphorylation of PGC-lalpha [J]. Proc Natl Acad Sci U S [] .Eur J Nutr,66(1):69-74 KANZLEITER T. JAHNERT M. SCHULZE G. et al.. 2015 ASAGIRI M, SATO K. USAMI T, et al., 2005. Autoamplification of Exercise training alters dNA methylation patterns in genes related to 64《体育科学》2020 年(第 40 卷)第 4 期 3 结论与展望 一直以来,相关研究都在从力学刺激下的骨相关因 子、激素、信号通路变化等方面论证适量运动有益于维持 骨稳态,并大力推广运动科学健骨的理念,而表观遗传正 为运动这一外源性刺激引起的骨相关基因响应内外环境 变化,并呈现出时间和空间上的表达调控改变,提供了最 新探究角度。近年来,相关研究为骨健康和运动医学领 域积累了一定的表观遗传学资料,通过影响基因的表观 遗传修饰,影响骨相关基因的表达,可能是运动改善骨质 的良性机制之一。尽管将表观遗传修饰、运动和骨质代 谢直接联系起来的研究并不多见,但通过对文献的整理 可以看出,运动能显著改变 DNA 甲基化水平、组蛋白修饰 状态及非编码 RNA 的表达,当中的部分表观遗传修饰变 化与骨质代谢标志物、信号通路和关键基因的表达密切 相关。然而,关于表观遗传的诸多疑问仍未解决,如机体 表型与代谢性疾病的发生由基因遗传和表观遗传共同决 定,应如何区分和量化两者影响程度的多寡;不同运动项 目、时长、强度和频次与骨相关表观遗传修饰变化之间的 关联等有待长期实验进行验证。同时,运动对干细胞表 观遗传修饰的影响或将成为运动医学领域的新兴课题。 未来还可将慢性骨代谢疾病与生活环境、生活方式等表 观遗传修饰的决定因素相联系,从诱因入手以减少骨疾 病发生的可能。 参考文献: 曹鹏,2009. 不同强度跑台运动对老龄雌性大鼠骨量及骨代谢的影 响[J].北京体育大学学报,32(2):74-76. 马涛,李世昌,梁晓霞,等,2011. 上、下坡跑台运动对去卵巢小鼠骨 密度及骨组织形态计量学指标的影响[J]. 体育科学,31(1): 48-55. 王维,孟智启,石放雄,2012. 组蛋白修饰及其生物学效应[J].遗传, 34(7):19-27. 杨宜锜,汤亭亭,2019. SIRT1 信号通路对于骨代谢的调节作用[J]. 上海交通大学学报(医学版),39(11):1335-1340. 张奎,刘洋,马煜,等,2017.骨质疏松性骨折与相关基因多态性研究 进展[J].中国骨质疏松杂志,23(7):974-980. 张严焱,徐召霞,陈渝,等,2018.运动改善高血压肠系膜动脉 LTCC 和 BKCa 通道功能的表观遗传调控机制[J]. 体育科学,38(11): 39-49. BLOOMFIELD S A,2003.营养、运动和激素促进骨健康的作用[J]. 体育科学,23(1):133-137. AMJADI-MOHEB F,AKHAVAN-NIAKI H,2019. Wnt signaling pathway in osteoporosis:Epigenetic regulation,interaction with other signaling pathways,and therapeutic promises[J]. J Cell Physiol,15(1):1-10. ANDREOLI A,CELI M,VOLPE S L,et al.,2012. Long-term effect of exercise on bone mineral density and body composition in post￾menopausal ex-elite athletes:A retrospective study[J]. Eur J Clin Nutr,66(1):69-74. ASAGIRI M,SATO K,USAMI T,et al.,2005. Autoamplification of NFATc1 expression determines its essential role in bone homeostasis [J]. J Exp Med,202(9):1261-1269. BÄCKESJÖ C M,LI Y,LINDGREN U,et al.,2006. Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells[J]. J Bone Miner Res,21(7):993-1002. BIN Z,JUNFENG Z,JIAO L,et al.,2015. microRNA-103a functions as a mechanosensitive microRNA to inhibit bone formation through targeting Runx2[J]. J Bone Miner Res,30(2):330-345. BRYAN A D,MAGNAN R E,HOOPER A E,et al.,2013. Physical activity and differential methylation of breast cancer genes assayed from saliva:A preliminary investigation[J]. Ann Behav Med,45 (1):89-98. CANTLEY M D,ZANNETTINO A,BARTOLD P M,et al.,2017. Histone deacetylases (HDAC) in physiological and pathological bone remodelling[J]. Bone,95:162-174. CHENG V K,AU P C,TAN K C,et al.,2018. microRNA and human bone Health[J]. JBMR Plus,3(1):2-13. COHENKFIR E,ARTSI H,LEVIN A,et al.,2011. Sirt1 is a regulator of bone mass and a repressor of Sost encoding for sclerostin,a bone formation inhibitor[J]. Endocrinol,152(12): 4514-4524. DENHAM J,OBRIEN B J,HARVEY J T,et al.,2015. Genome￾wide sperm DNA methylation changes after 3 months of exercise training in humans[J]. Epigenomics,7(5):717-731. DOMANSKA-SENDEROWSKA D,LAGUETTE M N,JEGIER A, et al.,2019. microRNA profile and adaptive response to exercise training:A review[J]. Int J Sports Med,40(4):227-235. EHLERT T,SIMON P,MOSER D A,2013. Epigenetics in sports[J]. Sports Med,43(2):93-110. FARSANI Z H,BANITABLEBI E,FARAMARZI M,et al.,2019. Effects of different intensities of strength and endurance training on some osteometabolic miRNAs,Runx2 and PPARγ in bone marrow of old male wistar rats[J]. Mol Biol Rep,46(2):2513-2521. FERRARA N,RINALDI B,CORBI G,et al.,2008. Exercise training promotes SIRT1 activity in aged rats[J]. Rejuvenati Res,11(1): 139-150. GAVIN K M,KOHRT W M,KLEMM D J,et al.,2018. Modulation of energy expenditure by estrogens and exercise in women[J]. Exerc Sport Sci Rev,46(4):232-239. GORDON J A,HASSAN M Q,KOSS M,et al.,2011. Epigenetic regulation of early osteogenesis and mineralized tissue formation by a HOXA10-PBX1-associated complex[J]. Cells Tissues Organs,194 (2-4):146-150. GRUNSTEIN M,1997. Histone acetylation in chromatin structure and transcription[J]. Nature,389(6649):349-352. HE L, VAN Roie E , BOGAERTS A, et al.,2018. Genetic predisposition score predicts the increases of knee strength and muscle mass after one-year exercise in healthy elderly[J]. Exp Gerontol,111:17-26. JÄGER S,HANDSCHIN C,ST-PIERRE J,et al.,2007. AMP￾activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha[J]. Proc Natl Acad Sci U S A,104(29):12017-12022. KANZLEITER T, JÄHNERT M, SCHULZE G, et al.,2015. Exercise training alters DNA methylation patterns in genes related to 64
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