国际口腔医学杂志 ›› 2021, Vol. 48 ›› Issue (2): 198-204.doi: 10.7518/gjkq.2021032

• 综述 • 上一篇    下一篇

脑和肌肉芳香烃受体核转运样蛋白1基因调控口腔及全身骨代谢的作用

邓诗勇(),宫苹,谭震()   

  1. 口腔疾病研究国家重点实验室 国家口腔疾病临床医学研究中心 四川大学华西口腔医院种植科 成都 610041
  • 收稿日期:2020-07-12 修回日期:2020-11-22 出版日期:2021-03-01 发布日期:2021-03-17
  • 通讯作者: 谭震
  • 作者简介:邓诗勇,硕士,Email: deng_sy@foxmail.com

Effects of brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 gene on the regulation of oral and systemic bone metabolism

Deng Shiyong(),Gong Ping,Tan Zhen()   

  1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Implantation, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2020-07-12 Revised:2020-11-22 Online:2021-03-01 Published:2021-03-17
  • Contact: Zhen Tan

摘要:

近日钟基因调控哺乳动物的昼夜节律,脑和肌肉芳香烃受体核转运样蛋白1(Bmal1)基因作为其核心组分之一,与多种生物行为活动密切相关,近年来,其在调控骨代谢方面具有的重要作用也受到越来越多的关注。Bmal1基因可通过下游多种信号通路的介导,分别参与调节骨相关成骨细胞、破骨细胞及软骨细胞等细胞的生理活动,进而影响如骨质疏松、骨关节炎等骨代谢相关疾病,同时也在颌骨的生理病理过程中发挥作用。本文就Bmal1基因调控骨代谢的研究进展作一综述,为口腔及全身相关骨代谢疾病的诊疗提供可能思路。

关键词: 脑和肌肉芳香烃受体核转运样蛋白1基因, 骨发育, 间充质干细胞, 代谢性骨疾病

Abstract:

The circadian clock gene regulates the circadian rhythm of mammals. As one of its core components, the Bmal1 gene is related to various biological behavioural activities. The role of this gene in bone metabolism has received increasing attention. The Bmal1 gene could be involved in the regulation of the physiological activities of osteoblasts, osteoclasts and chondrocytes related to bone metabolism through the downstream signalling pathways. These phenomena affect bone metabolism-related diseases, such as osteoporosis and osteoarthritis. The Bmal1 gene simultaneously plays a role in the physiological and pathological processes of the jaw. In this article, the development in the study of the Bmal1 gene regulating the physiology and pathology of bone tissue is reviewed. The results provide possible concepts for the treatment of oral and systemic bone metabolism-related diseases.

Key words: brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein 1 gene, bone development, marrow mesenchymal stem cells, metabolic bone disease

中图分类号: 

  • R34
[1] Berendsen AD, Olsen BR. Bone development[J]. Bone, 2015,80:14-18.
pmid: 26453494
[2] Rodan GA, Martin TJ. Therapeutic approaches to bone diseases[J]. Science, 2000,289(5484):1508-1514.
doi: 10.1126/science.289.5484.1508 pmid: 10968781
[3] Chen GJ, Tang QM, Yu SL, et al. The biological function of BMAL1 in skeleton development and disorders[J]. Life Sci, 2020,253:117636.
doi: 10.1016/j.lfs.2020.117636 pmid: 32251631
[4] Ma ZM, Jin XX, Qian Z, et al. Deletion of clock gene Bmal1 impaired the chondrocyte function due to disruption of the HIF1α-VEGF signaling pathway[J]. Cell Cycle, 2019,18(13):1473-1489.
doi: 10.1080/15384101.2019.1620572 pmid: 31107137
[5] Takarada T, Xu C, Ochi H, et al. Bone resorption is regulated by circadian clock in osteoblasts[J]. J Bone Miner Res, 2017,32(4):872-881.
doi: 10.1002/jbmr.3053 pmid: 27925286
[6] Tang ZH, Xu TY, Li YH, et al. Inhibition of CRY2 by STAT3/miRNA-7-5p promotes osteoblast diffe-rentiation through upregulation of CLOCK/BMAL1/P300 expression[J]. Mol Ther Nucleic Acids, 2020,19:865-876.
doi: 10.1016/j.omtn.2019.12.020 pmid: 31982773
[7] Truong KK, Lam MT, Grandner MA, et al. Timing matters: circadian rhythm in sepsis, obstructive lung disease, obstructive sleep apnea, and cancer[J]. Ann Am Thorac Soc, 2016,13(7):1144-1154.
doi: 10.1513/AnnalsATS.201602-125FR pmid: 27104378
[8] Wu XY, Yu G, Parks H, et al. Circadian mechanisms in murine and human bone marrow mesenchymal stem cells following dexamethasone exposure[J]. Bone, 2008,42(5):861-870.
doi: 10.1016/j.bone.2007.12.226
[9] McElderry JD, Zhao GS, Khmaladze A, et al. Trac-king circadian rhythms of bone mineral deposition in murine calvarial organ cultures[J]. J Bone Miner Res, 2013,28(8):1846-1854.
doi: 10.1002/jbmr.1924 pmid: 23505073
[10] Barinaga M. Circadian rhythms. Two feedback loops run mammalian clock[J]. Science, 2000,288(5468):943-944.
doi: 10.1126/science.288.5468.943a pmid: 10841707
[11] Janjić K, Kurzmann C, Moritz A, et al. Expression of circadian core clock genes in fibroblasts of human gingiva and periodontal ligament is modulated by L-mimosine and hypoxia in monolayer and sphe-roid cultures[J]. Arch Oral Biol, 2017,79:95-99.
doi: 10.1016/j.archoralbio.2017.03.007 pmid: 28350992
[12] Janjić K, Kurzmann C, Moritz A, et al. Core circa-dian clock gene expression in human dental pulp-derived cells in response to L-mimosine, hypoxia and echinomycin[J]. Eur J Oral Sci, 2018,126(4):263-271.
pmid: 30006964
[13] Rahman S, Kraljević Pavelić S, Markova-Car E. Circadian (de)regulation in head and neck squamous cell carcinoma[J]. Int J Mol Sci, 2019,20(11):E2662.
doi: 10.3390/ijms20112662 pmid: 31151182
[14] Kondratov RV, Kondratova AA, Gorbacheva VY, et al. Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock[J]. Genes Dev, 2006,20(14):1868-1873.
doi: 10.1101/gad.1432206 pmid: 16847346
[15] Yuan GS, Hua BX, Yang Y, et al. The circadian GeneClockRegulates bone formation via PDIA3[J]. J Bone Miner Res, 2017,32(4):861-871.
doi: 10.1002/jbmr.3046 pmid: 27883226
[16] Zvonic S, Ptitsyn AA, Kilroy G, et al. Circadian oscillation of gene expression in murine calvarial bone[J]. J Bone Miner Res, 2007,22(3):357-365.
pmid: 17144790
[17] Tonna EA, Singh IJ, Sandhu HS. Autoradiographic investigation of circadian rhythms in alveolar bone periosteum and cementum in young mice[J]. Histol Histopathol, 1987,2(2):129-133.
pmid: 2980712
[18] Hilbert DA, Memmert S, Marciniak J, et al. Molecular biology of periodontal ligament fibroblasts and orthodontic tooth movement: evidence and possible role of the circadian rhythm[J]. J Orofac Orthop, 2019,80(6):336-347.
doi: 10.1007/s00056-019-00195-5 pmid: 31650205
[19] Zhao JJ, Zhou X, Tang QM, et al. BMAL1 deficiency contributes to mandibular dysplasia by upregula-ting MMP3[J]. Stem Cell Reports, 2018,10(1):180-195.
doi: 10.1016/j.stemcr.2017.11.017 pmid: 29276151
[20] Chen YJ, Xu XM, Tan Z, et al. Age-related BMAL1 change affects mouse bone marrow stromal cell proliferation and osteo-differentiation potential[J]. Arch Med Sci, 2012,8(1):30-38.
doi: 10.5114/aoms.2012.27277 pmid: 22457671
[21] Guo BY, Chatterjee S, Li LF, et al. The clock gene, brain and muscle arnt-like 1, regulates adipogenesis via Wnt signaling pathway[J]. FASEB J, 2012,26(8):3453-3463.
doi: 10.1096/fj.12-205781 pmid: 22611086
[22] He Y, Chen Y, Zhao Q, et al. Roles of brain and muscle arnt-like 1 and Wnt antagonist Dkk1 during osteogenesis of bone marrow stromal cells[J]. Cell Prolif, 2013,46(6):644-653.
doi: 10.1111/cpr.12075 pmid: 24460718
[23] Huang ZF, Wei H, Wang X, et al. Icariin promotes osteogenic differentiation of BMSCs by upregula-ting BMAL1 expression via BMP signaling[J]. Mol Med Rep, 2020,21(3):1590-1596.
doi: 10.3892/mmr.2020.10954 pmid: 32016461
[24] He Y, Lin FW, Chen YQ, et al. Overexpression of the circadian clock gene Rev-erbα affects murine bone mesenchymal stem cell proliferation and osteogenesis[J]. Stem Cells Dev, 2015,24(10):1194-1204.
[25] 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.
[26] Li XG, Liu N, Gu B, et al. BMAL1 regulates ba-lance of osteogenic-osteoclastic function of bone marrow mesenchymal stem cells in type 2 diabetes mellitus through the NF-κB pathway[J]. Mol Biol Rep, 2018,45(6):1691-1704.
doi: 10.1007/s11033-018-4312-7 pmid: 30259246
[27] Terheyden H, Lang NP, Bierbaum S, et al. Osseointegration-communication of cells[J]. Clin Oral Implants Res, 2012,23(10):1127-1135.
doi: 10.1111/j.1600-0501.2011.02327.x pmid: 22092345
[28] Mengatto CM, Mussano F, Honda Y, et al. Circa-dian rhythm and cartilage extracellular matrix genes in osseointegration: a genome-wide screening of implant failure by vitamin D deficiency[J]. PLoS One, 2011,6(1):e15848.
doi: 10.1371/journal.pone.0015848 pmid: 21264318
[29] Hassan N, McCarville K, Morinaga K, et al. Tita-nium biomaterials with complex surfaces induced aberrant peripheral circadian rhythms in bone marrow mesenchymal stromal cells[J]. PLoS One, 2017,12(8):e0183359.
pmid: 28817668
[30] Lin FW, Chen YJ, Li XL, et al. Over-expression of circadian clock gene Bmal1 affects proliferation and the canonical Wnt pathway in NIH-3T3 cells[J]. Cell Biochem Funct, 2013,31(2):166-172.
pmid: 22961668
[31] Lee S, Donehower LA, Herron AJ, et al. Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice[J]. PLoS One, 2010,5(6):e10995.
pmid: 20539819
[32] Fei CM, Zhao YS, Guo J, et al. Senescence of bone marrow mesenchymal stromal cells is accompanied by activation of p53/p21 pathway in myelodysplastic syndromes[J]. Eur J Haematol, 2014,93(6):476-486.
pmid: 24889123
[33] Mao XF, Li XG, Hu W, et al. Downregulated brain and muscle aryl hydrocarbon receptor nuclear translocator-like protein-1 inhibits osteogenesis of BMSCs through p53 in type 2 diabetes mellitus[J]. Biol Open, 2020, 9(7): bio051482.
doi: 10.1242/bio.051482 pmid: 32554484
[34] Wu YL, Tang DB, Liu N, et al. Reciprocal regulation between the circadian clock and hypoxia signa-ling at the genome level in mammals[J]. Cell Metab, 2017,25(1):73-85.
[35] Stevenson S, Hunziker EB, Herrmann W, et al. Is longitudinal bone growth influenced by diurnal va-riation in the mitotic activity of chondrocytes of the growth plate[J]. J Orthop Res, 1990,8(1):132-135.
doi: 10.1002/jor.1100080117 pmid: 2293628
[36] Gossan N, Zeef L, Hensman J, et al. The circadian clock in murine chondrocytes regulates genes controlling key aspects of cartilage homeostasis[J]. Arthritis Rheum, 2013,65(9):2334-2345.
doi: 10.1002/art.38035 pmid: 23896777
[37] Hand LE, Dickson SH, Freemont AJ, et al. The circadian regulator Bmal1 in joint mesenchymal cells regulates both joint development and inflammatory arthritis[J]. Arthritis Res Ther, 2019,21(1):5.
pmid: 30612576
[38] Dudek M, Gossan N, Yang N, et al. The chondrocyte clock gene Bmal1 controls cartilage homeostasis and integrity[J]. J Clin Invest, 2016,126(1):365-376.
doi: 10.1172/JCI82755 pmid: 26657859
[39] Schipani E, Maes C, Carmeliet G, et al. Regulation of osteogenesis-angiogenesis coupling by HIFs and VEGF[J]. J Bone Miner Res, 2009,24(8):1347-1353.
doi: 10.1359/jbmr.090602 pmid: 19558314
[40] Akagi R, Akatsu Y, Fisch KM, et al. Dysregulated circadian rhythm pathway in human osteoarthritis: NR1D1 and BMAL1 suppression alters TGF-β signaling in chondrocytes[J]. Osteoarthritis Cartilage, 2017,25(6):943-951.
doi: 10.1016/j.joca.2016.11.007 pmid: 27884645
[41] Hofbauer LC, Heufelder AE. Role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in bone cell biology[J]. J Mol Med (Berl), 2001,79(5/6):243-253.
[42] Negishi-Koga T, Shinohara M, Komatsu N, et al. Suppression of bone formation by osteoclastic expression of semaphorin 4D[J]. Nat Med, 2011,17(11):1473-1480.
doi: 10.1038/nm.2489 pmid: 22019888
[43] Qian Z, Zhang Y, Kang XM, et al. Postnatal conditional deletion of Bmal1 in osteoblasts enhances trabecular bone formation via increased BMP2 signals[J]. J Bone Miner Res, 2020,35(8):1481-1493.
doi: 10.1002/jbmr.4017 pmid: 32212389
[44] Zhou X, Yu R, Long YL, et al. BMAL1 deficiency promotes skeletal mandibular hypoplasia via OPG downregulation[J]. Cell Prolif, 2018,51(5):e12470.
doi: 10.1111/cpr.12470 pmid: 30117209
[45] Tsang K, Liu HM, Yang Y, et al. Defective circadian control in mesenchymal cells reduces adult bone mass in mice by promoting osteoclast function[J]. Bone, 2019,121:172-180.
doi: 10.1016/j.bone.2019.01.016 pmid: 30659979
[46] 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.
doi: 10.1002/jbmr.2803 pmid: 26841172
[47] Janjić K, Kurzmann C, Moritz A, et al. Expression of circadian core clock genes in fibroblasts of human gingiva and periodontal ligament is modulated by L-mimosine and hypoxia in monolayer and sphe-roid cultures[J]. Arch Oral Biol, 2017,79:95-99.
pmid: 28350992
[48] Xie MR, Tang QM, Nie JM, et al. BMAL1-downregulation aggravates Porphyromonas gingivalis-induced atherosclerosis by encouraging oxidative stress[J]. Circ Res, 2020,126(6):e15-e29.
pmid: 32078488
[49] Carcuac O, Abrahamsson I, Albouy JP, et al. Experimental periodontitis and peri-implantitis in dogs[J]. Clin Oral Implants Res, 2013,24(4):363-371.
pmid: 23176551
[50] Zhang J, Li ZG, Si YM, et al. The difference on the osteogenic differentiation between periodontal ligament stem cells and bone marrow mesenchymal stem cells under inflammatory microenviroments[J]. Differentiation, 2014,88(4/5):97-105.
[51] Zhang L, Wang PH, Mei SL, et al. In vivo alveolar bone regeneration by bone marrow stem cells/fibrin glue composition[J]. Arch Oral Biol, 2012,57(3):238-244.
[52] Early JO, Menon D, Wyse CA, et al. Circadian clock protein BMAL1 regulates IL-1β in macrophages via NRF2[J]. Proc Natl Acad Sci U S A, 2018,115(36):E8460-E8468.
pmid: 30127006
[53] Smith BJ, Sutton GM, Wu X, et al. Ovariectomy and genes encoding core circadian regulatory proteins in murine bone[J]. Osteoporos Int, 2011,22(5):1633-1639.
doi: 10.1007/s00198-010-1325-z pmid: 20593165
[54] Tahara Y, Takatsu Y, Shiraishi T, et al. Age-related circadian disorganization caused by sympathetic dysfunction in peripheral clock regulation[J]. NPJ Aging Mech Dis, 2017,3:16030.
doi: 10.1038/npjamd.2016.30 pmid: 28721279
[55] Kojetin DJ, Burris TP. REV-ERB and ROR nuclear receptors as drug targets[J]. Nat Rev Drug Discov, 2014,13(3):197-216.
doi: 10.1038/nrd4100 pmid: 24577401
[56] Li Y, Zhou J, Wu Y, et al. Association of osteoporosis with genetic variants of circadian genes in Chinese geriatrics[J]. Osteoporos Int, 2016,27(4):1485-1492.
doi: 10.1007/s00198-015-3391-8 pmid: 26564225
[57] Snelling SJ, Forster A, Mukherjee S, et al. The chondrocyte-intrinsic circadian clock is disrupted in human osteoarthritis[J]. Chronobiol Int, 2016,33(5):574-579.
[58] He D, An YX, Li YH, et al. RNA sequencing reveals target genes of temporomandibular joint osteoarthritis in rats after the treatment of low-intensity pulsed ultrasound[J]. Gene, 2018,672:126-136.
doi: 10.1016/j.gene.2018.06.002 pmid: 29885465
[59] Doody KM, Bottini N. Chondrocyte clocks make cartilage time-sensitive material[J]. J Clin Invest, 2016,126(1):38-39.
pmid: 26657854
[60] Saito T, Kawaguchi H. HIF-2α as a possible therapeutic target of osteoarthritis[J]. Osteoarthritis Cartilage, 2010,18(12):1552-1556.
doi: 10.1016/j.joca.2010.10.006 pmid: 20950696
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[4] 宋红. 青少年牙周炎外周血分叶核粒细胞的趋化功能[J]. 国际口腔医学杂志, 1999, 26(06): .
[5] 高卫民,李幸红. 发达国家牙医学院口腔种植学教学现状[J]. 国际口腔医学杂志, 1999, 26(06): .
[6] 侯锐. 正畸患者釉白斑损害的纵向激光荧光研究[J]. 国际口腔医学杂志, 1999, 26(05): .
[7] 轩东英. 不同赋形剂对氢氧化钙抗菌效果的影响[J]. 国际口腔医学杂志, 1999, 26(05): .
[8] 房兵. 唇腭裂新生儿前颌骨矫正方法及对上颌骨生长发育的影响[J]. 国际口腔医学杂志, 1999, 26(05): .
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