节律基因调控成骨和破骨活动机制的研究进展
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摘要
人的近日节律系统是以节律基因为核心,调控24 h体内多种节律性生理活动的主要机制。成骨活动与破骨活动两者的动态平衡是骨组织行使功能的基础。节律基因与成骨和破骨活动关系密切,在骨重建中起到重要调控作用,可能为骨再生医学的调控靶点。本文将综述近日节律系统的构成及近年研究节律基因调控成骨和破骨活动机制的新进展,可能为骨再生重建治疗提供新的思路。
The internal circadian timing system of human is a major regulatory network mainly interacting circadian genes for regulating 24h rhythms of many metabolic and physiological processes. The dynamic balance of osteogenesis and bone resorption is the foundation of normal bone function. The circadian genes, which are closely related to osteogenesis and bone resorption, play an essential regulatory role in bone remolding and may be targets of bone regenerative medicine.This review focuses on the circadian timing system structure and the recent progress of research on regulatory mechanism of osteogenesis and bone resorption. We aim to possibly determine a novel approach for bone reconstruction and regenerative therapy.
The internal circadian timing system of human is a major regulatory network mainly interacting circadian genes for regulating 24h rhythms of many metabolic and physiological processes. The dynamic balance of osteogenesis and bone resorption is the foundation of normal bone function. The circadian genes, which are closely related to osteogenesis and bone resorption, play an essential regulatory role in bone remolding and may be targets of bone regenerative medicine.This review focuses on the circadian timing system structure and the recent progress of research on regulatory mechanism of osteogenesis and bone resorption. We aim to possibly determine a novel approach for bone reconstruction and regenerative therapy.
引文
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[4]Maury E,Hong HK,Bass J.Circadian disruption in the pathogenesis of metabolic syndrome[J].Diabetes Metab,2014,40(5):338-346.
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[12]Yoo SH,Yamazaki S,Lowrey PL,et al.PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues[J].Proc Natl Acad Sci U SA,2004,101(15):5339-5346.
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[15]Luo W,Li Y,Tang CH,et al.CLOCK deubiquitylation by USP8 inhibits CLK/CYC transcription in Drosophila[J].Genes Dev,2012,26(22):2536-2549.
[16]Robles MS,Humphrey SJ,Mann M.Phosphorylation is a central mechanism for circadian control of metabolism and physiology[J].Cell Metab,2017,25(1):118-127.
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[19]Weger M,Diotel N,Dorsemans AC,et al.Stem cells and the circadian clock[J].Dev Biol,2017,431(2):111-123.
[20]Boucher H,Vanneaux V,Domet T,et al.Circadian clock genes modulate human bone marrow mesenchymal stem cell differentiation,migration and cell cycle[J].PLoS One,2016,11(1):e0146674.
[21]Meyer T,Kneissel M,Mariani J,et al.In vitro and in vivo evidence for orphan nuclear receptor RORalpha function in bone metabolism[J].Proc Natl Acad Sci U S A,2000,97(16):9197-9202.
[22]He Y,Lin F,Chen Y,et al.Overexpression of the circadian clock gene Rev-erbαaffects murine bone mesenchymal stem cell proliferation and osteogenesis[J].Stem Cells Dev,2015,24(10):1194-1204.
[23]Li X,Liu N,Wang Y,et al.Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 cooperates with glycogen synthase kinase-3βto regulate osteogenesis of bone-marrow mesenchymal stem cells in type 2 diabetes[J].Mol Cell Endocrinol,2017,440:93-105.
[24]Sahar S,Zocchi L,Kinoshita C,et al.Regulation of BMAL1 protein stability and circadian function by GSK3beta-mediated phosphorylation[J].PLoS One,2010,5(1):e8561.
[25]Marcheva B,Ramsey KM,Buhr ED,et al.Disruption of the clock components CLOCK and BMAL1leads to hypoinsulinaemia and diabetes[J].Nature,2010,466(7306):627-631.
[26]Sato F,Sato H,Jin D,et al.Smad3 and Snail show circadian expression in human gingival fibroblasts,human mesenchymal stem cell,and in mouse liver[J].Biochem Biophys Res Commun,2012,419(2):441-446.
[27]Spengler ML,Kuropatwinski KK,Comas M,et al.Core circadian protein CLOCK is a positive regulator of NF-κB-mediated transcription[J].Proc Natl Acad Sci U S A,2012,109(37):E2457-E2465.
[28]龙洁,田卫东,郑晓辉,等.牵张成骨对山羊下颌骨成骨细胞增殖节律的影响[J].华西口腔医学杂志,2003,21(2):144-146,152.Long J,Tian WD,Zheng XH,et al.Effect of distraction osteogenesis on circadian rhythm of proliferation index of mandibular osteoblast in goat[J].West Chin J Stomatol,2003,21(2):144-146,152.
[29]Wang Y,Nizkorodov A,Riemenschneider K,et al.Impaired bone formation in Pdia3 deficient mice[J].PLoS One,2014,9(11):e112708.
[30]Santana-Codina N,Carretero R,Sanz-Pamplona R,et al.A transcriptome-proteome integrated network identifies endoplasmic reticulum thiol oxidoreductase(ERp57)as a hub that mediates bone metastasis[J].Mol Cell Proteomics,2013,12(8):2111-2125.
[31]Yuan G,Hua B,Yang Y,et al.The circadian gene clock regulates bone formation via PDIA3[J].J Bone Miner Res,2017,32(4):861-871.
[32]Fu L,Patel MS,Karsenty G.The circadian modulation of leptin-controlled bone formation[J].Prog Brain Res,2006,153:177-188.
[33]Hirai T.Regulation of clock genes by adrenergic receptor signaling in osteoblasts[J].Neurochem Res,2018,43(1):120-126.
[34]Hirai T,Tanaka K,Togari A.β-adrenergic receptor signaling regulates Ptgs2 by driving circadian gene expression in osteoblasts[J].J Cell Sci,2014,127(Pt17):3711-3719.
[35]Hirai T,Tanaka K,Togari A.α1-adrenergic receptor signaling in osteoblasts regulates clock genes and bone morphogenetic protein 4 expression through up-regulation of the transcriptional factor nuclear factor IL-3(Nfil3)/E4 promoter-binding protein 4(E4BP4)[J].J Biol Chem,2014,289(24):17174-17183.
[36]Takeda S,Elefteriou F,Levasseur R,et al.Leptin regulates bone formation via the sympathetic nervous system[J].Cell,2002,111(3):305-317.
[37]Min HY,Kim KM,Wee G,et al.Bmal1 induces osteoblast differentiation via regulation of BMP2expression in MC3T3-E1 cells[J].Life Sci,2016,162:41-46.
[38]Cappellen D,Luong-Nguyen NH,Bongiovanni S,et al.Transcriptional program of mouse osteoclast differentiation governed by the macrophage colonystimulating factor and the ligand for the receptor activator of NFkappa B[J].J Biol Chem,2002,277(24):21971-21982.
[39]Xu C,Ochi H,Fukuda T,et al.Circadian clock regulates bone resorption in mice[J].J Bone Miner Res,2016,31(7):1344-1355.
[40]Fujihara Y,Kondo H,Noguchi T,et al.Glucocorticoids mediate circadian timing in peripheral osteoclasts resulting in the circadian expression rhythm of osteoclast-related genes[J].Bone,2014,61:1-9.
[41]Kearns AE,Khosla S,Kostenuik PJ.Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease[J].Endocr Rev,2008,29(2):155-192.
[2]Fuhr L,Abreu M,Pett P,et al.Circadian systems biology:when time matters[J].Comput Struct Biotechnol J,2015,13:417-426.
[3]Borgs L,Beukelaers P,Vandenbosch R,et al.Cell“circadian”cycle:new role for mammalian core clock genes[J].Cell Cycle,2009,8(6):832-837.
[4]Maury E,Hong HK,Bass J.Circadian disruption in the pathogenesis of metabolic syndrome[J].Diabetes Metab,2014,40(5):338-346.
[5]Mazzoccoli G,Pazienza V,Vinciguerra M.Clock genes and clock-controlled genes in the regulation of metabolic rhythms[J].Chronobiol Int,2012,29(3):227-251.
[6]Jagannath A,Taylor L,Wakaf Z,et al.The genetics of circadian rhythms,sleep and health[J].Hum Mol Genet,2017,26(R2):R128-R138.
[7]Khaper N,Bailey CDC,Ghugre NR,et al.Implications of disturbances in circadian rhythms for cardiovascular health:a new frontier in free radical biology[J].Free Radic Biol Med,2018,119:85-92.
[8]Samsa WE,Vasanji A,Midura RJ,et al.Deficiency of circadian clock protein BMAL1 in mice results in a low bone mass phenotype[J].Bone,2016,84:194-203.
[9]Komoto S,Kondo H,Fukuta O,et al.Comparison ofβ-adrenergic and glucocorticoid signaling on clock gene and osteoblast-related gene expressions in human osteoblast[J].Chronobiol Int,2012,29(1):66-74.
[10]Song C,Wang J,Kim B,et al.Insights into the role of circadian rhythms in bone metabolism:a promising intervention target[J].Biomed Res Int,2018,2018:9156478.
[11]Reppert SM,Weaver DR.Coordination of circadian timing in mammals[J].Nature,2002,418(6901):935-941.
[12]Yoo SH,Yamazaki S,Lowrey PL,et al.PERIOD2::LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues[J].Proc Natl Acad Sci U SA,2004,101(15):5339-5346.
[13]Lowrey PL,Takahashi JS.Mammalian circadian biology:elucidating genome-wide levels of temporal organization[J].Annu Rev Genomics Hum Genet,2004,5:407-441.
[14]Takahashi JS.Molecular components of the circadian clock in mammals[J].Diabetes Obes Metab,2015,17(Suppl 1):6-11.
[15]Luo W,Li Y,Tang CH,et al.CLOCK deubiquitylation by USP8 inhibits CLK/CYC transcription in Drosophila[J].Genes Dev,2012,26(22):2536-2549.
[16]Robles MS,Humphrey SJ,Mann M.Phosphorylation is a central mechanism for circadian control of metabolism and physiology[J].Cell Metab,2017,25(1):118-127.
[17]Preitner N,Damiola F,Lopez-Molina L,et al.The orphan nuclear receptor REV-ERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator[J].Cell,2002,110(2):251-260.
[18]Murray IR,West CC,Hardy WR,et al.Natural history of mesenchymal stem cells,from vessel walls to culture vessels[J].Cell Mol Life Sci,2014,71(8):1353-1374.
[19]Weger M,Diotel N,Dorsemans AC,et al.Stem cells and the circadian clock[J].Dev Biol,2017,431(2):111-123.
[20]Boucher H,Vanneaux V,Domet T,et al.Circadian clock genes modulate human bone marrow mesenchymal stem cell differentiation,migration and cell cycle[J].PLoS One,2016,11(1):e0146674.
[21]Meyer T,Kneissel M,Mariani J,et al.In vitro and in vivo evidence for orphan nuclear receptor RORalpha function in bone metabolism[J].Proc Natl Acad Sci U S A,2000,97(16):9197-9202.
[22]He Y,Lin F,Chen Y,et al.Overexpression of the circadian clock gene Rev-erbαaffects murine bone mesenchymal stem cell proliferation and osteogenesis[J].Stem Cells Dev,2015,24(10):1194-1204.
[23]Li X,Liu N,Wang Y,et al.Brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 cooperates with glycogen synthase kinase-3βto regulate osteogenesis of bone-marrow mesenchymal stem cells in type 2 diabetes[J].Mol Cell Endocrinol,2017,440:93-105.
[24]Sahar S,Zocchi L,Kinoshita C,et al.Regulation of BMAL1 protein stability and circadian function by GSK3beta-mediated phosphorylation[J].PLoS One,2010,5(1):e8561.
[25]Marcheva B,Ramsey KM,Buhr ED,et al.Disruption of the clock components CLOCK and BMAL1leads to hypoinsulinaemia and diabetes[J].Nature,2010,466(7306):627-631.
[26]Sato F,Sato H,Jin D,et al.Smad3 and Snail show circadian expression in human gingival fibroblasts,human mesenchymal stem cell,and in mouse liver[J].Biochem Biophys Res Commun,2012,419(2):441-446.
[27]Spengler ML,Kuropatwinski KK,Comas M,et al.Core circadian protein CLOCK is a positive regulator of NF-κB-mediated transcription[J].Proc Natl Acad Sci U S A,2012,109(37):E2457-E2465.
[28]龙洁,田卫东,郑晓辉,等.牵张成骨对山羊下颌骨成骨细胞增殖节律的影响[J].华西口腔医学杂志,2003,21(2):144-146,152.Long J,Tian WD,Zheng XH,et al.Effect of distraction osteogenesis on circadian rhythm of proliferation index of mandibular osteoblast in goat[J].West Chin J Stomatol,2003,21(2):144-146,152.
[29]Wang Y,Nizkorodov A,Riemenschneider K,et al.Impaired bone formation in Pdia3 deficient mice[J].PLoS One,2014,9(11):e112708.
[30]Santana-Codina N,Carretero R,Sanz-Pamplona R,et al.A transcriptome-proteome integrated network identifies endoplasmic reticulum thiol oxidoreductase(ERp57)as a hub that mediates bone metastasis[J].Mol Cell Proteomics,2013,12(8):2111-2125.
[31]Yuan G,Hua B,Yang Y,et al.The circadian gene clock regulates bone formation via PDIA3[J].J Bone Miner Res,2017,32(4):861-871.
[32]Fu L,Patel MS,Karsenty G.The circadian modulation of leptin-controlled bone formation[J].Prog Brain Res,2006,153:177-188.
[33]Hirai T.Regulation of clock genes by adrenergic receptor signaling in osteoblasts[J].Neurochem Res,2018,43(1):120-126.
[34]Hirai T,Tanaka K,Togari A.β-adrenergic receptor signaling regulates Ptgs2 by driving circadian gene expression in osteoblasts[J].J Cell Sci,2014,127(Pt17):3711-3719.
[35]Hirai T,Tanaka K,Togari A.α1-adrenergic receptor signaling in osteoblasts regulates clock genes and bone morphogenetic protein 4 expression through up-regulation of the transcriptional factor nuclear factor IL-3(Nfil3)/E4 promoter-binding protein 4(E4BP4)[J].J Biol Chem,2014,289(24):17174-17183.
[36]Takeda S,Elefteriou F,Levasseur R,et al.Leptin regulates bone formation via the sympathetic nervous system[J].Cell,2002,111(3):305-317.
[37]Min HY,Kim KM,Wee G,et al.Bmal1 induces osteoblast differentiation via regulation of BMP2expression in MC3T3-E1 cells[J].Life Sci,2016,162:41-46.
[38]Cappellen D,Luong-Nguyen NH,Bongiovanni S,et al.Transcriptional program of mouse osteoclast differentiation governed by the macrophage colonystimulating factor and the ligand for the receptor activator of NFkappa B[J].J Biol Chem,2002,277(24):21971-21982.
[39]Xu C,Ochi H,Fukuda T,et al.Circadian clock regulates bone resorption in mice[J].J Bone Miner Res,2016,31(7):1344-1355.
[40]Fujihara Y,Kondo H,Noguchi T,et al.Glucocorticoids mediate circadian timing in peripheral osteoclasts resulting in the circadian expression rhythm of osteoclast-related genes[J].Bone,2014,61:1-9.
[41]Kearns AE,Khosla S,Kostenuik PJ.Receptor activator of nuclear factor kappaB ligand and osteoprotegerin regulation of bone remodeling in health and disease[J].Endocr Rev,2008,29(2):155-192.