Int J Stomatol

Int J Stomatol ›› 2019, Vol. 46 ›› Issue (3): 263-269.doi: 10.7518/gjkq.2019034

• Signalling Pathways • Previous Articles     Next Articles

Research progress on role of Hippo pathway in bone metabolism

Xinyuan Zhang,Bin Wang,Hui Yu,Liwen Zhu,Lin Xiang()   

  1. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Dept. of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, China
  • Received:2018-05-22 Revised:2019-01-16 Online:2019-05-01 Published:2019-06-05
  • Contact: Lin Xiang E-mail:dentistxiang@126.com
  • Supported by:
    This study was supported by National Natural Science Foundation of China(81701007);Sichuan Science and Technology Program(2018RZ0087);Fundamental Research Funds for the Central Universities(2017SCU12056);Fundamental Research Funds for the Central Universities(2018SCUH0006);China Postdoctoral Science Foundation(2018M631091);Youth Science Foundation of West China Hospital of Stomatology of Sichuan University(2016-11)

RichHTML

18

PDF (PC)

289

Abstract:

In mammals, the Hippo signalling pathway is highly conserved and regulates bone metabolism and maintains the essential physiological functions of bones. Mammalian sterile 20-like kinase 1/2, large tumour suppressor 1/2 and the Yes-associated protein/transcriptional coactivator with PDZ-binding motif are the core components of the Hippo signalling pathway. This pathway mediates the physiological functions of osteoblasts, osteoclasts and chondrocytes under the regulation of multiple transcription factors upstream and downstream. In this study, we highlight the recent research progress on the mechanism underlying bone metabolism in the Hippo signalling pathway. We hope that this review can provide new ideas and strategies for further investigations and treatment of bone metabolism-related diseases.

Key words: Hippo signaling pathway, mammalian sterile 20-like kinase, Yes associated protein, bone metabolism

CLC Number: 

  • Q257

TrendMD: 
[1] Harvey KF, Pfleger CM, Hariharan IK . The Drosophila Mst ortholog, hippo, restricts growth and cell proliferation and promotes apoptosis[J]. Cell, 2003,114(4):457-467.
doi: 10.1016/S0092-8674(03)00557-9 pmid: 12941274
[2] Justice RW, Zilian O, Woods DF , et al. The Drosophila tumor suppressor gene warts encodes a homolog of human myotonic dystrophy kinase and is required for the control of cell shape and proliferation[J]. Genes Dev, 1995,9(5):534-546.
doi: 10.1101/gad.9.5.534 pmid: 7698644
[3] Johnson R, Halder G . The two faces of Hippo: targeting the Hippo pathway for regenerative medicine and cancer treatment[J]. Nat Rev Drug Discov, 2014,13(1):63-79.
doi: 10.1038/nrd4161 pmid: 4167640
[4] Yu FX, Zhao B, Guan KL . Hippo pathway in organ size control, tissue homeostasis, and cancer[J]. Cell, 2015,163(4):811-828.
doi: 10.1016/j.cell.2015.10.044 pmid: 4638384
[5] Wang J, Martin JF . Hippo pathway: an emerging regulator of craniofacial and dental development[J]. J Dent Res, 2017,96(11):1229-1237.
doi: 10.1177/0022034517719886 pmid: 28700256
[6] Okamoto K, Nakashima T, Shinohara M , et al. Osteoimmunology: the conceptual framework unifying the immune and skeletal systems[J]. Physiol Rev, 2017,97(4):1295-1349.
doi: 10.1152/physrev.00036.2016 pmid: 28814613
[7] Scheel H, Hofmann K . A novel interaction motif, SARAH, connects three classes of tumor suppressor[J]. Curr Biol, 2003,13(23):R899-R900.
doi: 10.1016/j.cub.2003.11.007
[8] Gladden AB, Hebert AM, Schneeberger EE , et al. The NF2 tumor suppressor, Merlin, regulates epidermal development through the establishment of a junctional polarity complex[J]. Dev Cell, 2010,19(5):727-739.
doi: 10.1016/j.devcel.2010.10.008 pmid: 21074722
[9] Das Thakur M, Feng Y, Jagannathan R , et al. Ajuba LIM proteins are negative regulators of the Hippo signaling pathway[J]. Curr Biol, 2010,20(7):657-662.
doi: 10.1016/j.cub.2010.02.035 pmid: 20303269
[10] Hansen CG, Moroishi T, Guan KL . YAP and TAZ: a nexus for Hippo signaling and beyond[J]. Trends Cell Biol, 2015,25(9):499-513.
doi: 10.1016/j.tcb.2015.05.002 pmid: 26045258
[11] Lee J, Youn BU, Kim K , et al. Mst2 controls bone homeostasis by regulating osteoclast and osteoblast differentiation[J]. J Bone Miner Res, 2015,30(9):1597-1607.
doi: 10.1002/jbmr.2503 pmid: 257616702
[12] Oh S, Lee D, Kim T , et al. Crucial role for Mst1 and Mst2 kinases in early embryonic development of the mouse[J]. Mol Cell Biol, 2009,29(23):6309-6320.
doi: 10.1128/MCB.00551-09
[13] Katagiri K, Imamura M, Kinashi T . Spatiotemporal regulation of the kinase Mst1 by binding protein RAPL is critical for lymphocyte polarity and adhesion[J]. Nat Immunol, 2006,7(9):919-928.
doi: 10.1016/S0020-0190(99)00120-9 pmid: 16892067
[14] Zhou D, Medoff BD, Chen L , et al. The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of naïve T cells[J]. Proc Natl Acad Sci USA, 2008,105(51):20321-20326.
doi: 10.1073/pnas.0810773105 pmid: 19073936
[15] Mou F, Praskova M, Xia F , et al. The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes[J]. J Exp Med, 2012,209(4):741-759.
doi: 10.1084/jem.20111692 pmid: 22412158
[16] Salojin KV, Hamman BD, Chang WC , et al. Genetic deletion of Mst1 alters T cell function and protects against autoimmunity[J]. PLoS One, 2014,9(5):e98151.
doi: 10.1371/journal.pone.0098151
[17] Varelas X . The Hippo pathway effectors TAZ and YAP in development, homeostasis and disease[J]. Development, 2014,141(8):1614-1626.
doi: 10.1242/dev.102376 pmid: 24715453
[18] Zhu Y, Wu Y, Cheng J , et al. Pharmacological activation of TAZ enhances osteogenic differentiation and bone formation of adipose-derived stem cells[J]. Stem Cell Res, Ther, 2018,9(1):53.
doi: 10.1186/s13287-018-0799-z pmid: 29514703
[19] Pan H, Xie Y, Zhang Z , et al. YAP-mediated mechanotransduction regulates osteogenic and adipogenic differentiation of BMSCs on hierarchical structure[J]. Colloids Surf B Biointerfaces, 2017,152:344-353.
doi: 10.1016/j.colsurfb.2017.01.039 pmid: 28131959
[20] 王飞, 张慧宇, 窦予昕 , 等. 降钙素基因相关肽通过Hippo通路调控小鼠骨髓间充质干细胞成骨分化的实验研究[J]. 华西口腔医学杂志, 2016,34(3):286-290.
doi: 10.7518/hxkq.2016.03.014
Wang F, Zhang HY, Dou YX , et al. Calcitonin gene-related peptide-induced osteogenic differentiation of mouse bone marrow stromal cells through Hippo pathway in vitro[J]. West Chin J Stomatol, 2016,34(3):286-290.
doi: 10.7518/hxkq.2016.03.014
[21] Levaot N, Simoncic PD, Dimitriou ID , et al. 3BP2-deficient mice are osteoporotic with impaired osteoblast and osteoclast functions[J]. J Clin Invest, 2011,121(8):3244-3257.
doi: 10.1172/JCI45843 pmid: 3148735
[22] Matsumoto Y, La Rose J, Kent OA , et al. Reciprocal stabilization of ABL and TAZ regulates osteoblastogenesis through transcription factor RUNX2[J]. J Clin Invest, 2016,126(12):4482-4496.
doi: 10.1172/JCI87802 pmid: 27797343
[23] Kegelman CD, Mason DE, Dawahare JH , et al. Skeletal cell YAP and TAZ combinatorially promote bone development[J]. FASEB J, 2018,32(5):2706-2721.
doi: 10.1096/fj.201700872R pmid: 29401582
[24] Xiong J, Almeida M , O’Brien CA. The YAP/TAZ transcriptional co-activators have opposing effects at different stages of osteoblast differentiation[J]. Bone, 2018,112:1-9.
doi: 10.1016/j.bone.2018.04.001 pmid: 29626544
[25] Jiang J, Chang W, Fu Y , et al. SAV1 represses the development of human colorectal cancer by regulating the Akt-mTOR pathway in a YAP-dependent manner[J]. Cell Prolif, 2017,50(4). doi: 10.1111/cpr. 12351.
doi: 10.1111/cpr.12351 pmid: 28618450
[26] Zhao L, Guan H, Song C , et al. YAP1 is essential for osteoclastogenesis through a TEADs-dependent mechanism[J]. Bone, 2018,110:177-186.
doi: 10.1016/j.bone.2018.01.035 pmid: 29432919
[27] Nagase Y, Iwasawa M, Akiyama T , et al. Anti-apoptotic molecule Bcl-2 regulates the differentiation, activation, and survival of both osteoblasts and osteoclasts[J]. J Biol Chem, 2009,284(52):36659-36669.
doi: 10.1074/jbc.M109.016915 pmid: 19846553
[28] Li W, Dong S, Wei W , et al. The role of transcriptional coactivator TAZ in gliomas[J]. Oncotarget, 2016,7(50):82686-82699.
doi: 10.18632/oncotarget.12625 pmid: 27764783
[29] Karystinou A, Roelofs AJ, Neve A , et al. Yes-associated protein (YAP) is a negative regulator of chondrogenesis in mesenchymal stem cells[J]. Arthritis Res Ther, 2015,17:147.
doi: 10.1186/s13075-015-0639-9 pmid: 4449558
[30] Deng Y, Wu A, Li P , et al. Yap1 regulates multiple steps of chondrocyte differentiation during skeletal development and bone repair[J]. Cell Rep, 2016,14(9):2224-2237.
doi: 10.1016/j.celrep.2016.02.021 pmid: 26923596
[31] Yang B, Sun H, Song F , et al. YAP1 negatively regulates chondrocyte differentiation partly by activating the β-catenin signaling pathway[J]. Int J Biochem Cell Biol, 2017,87:104-113.
doi: 10.1016/j.biocel.2017.04.007 pmid: 28438716
[32] Li C, Wang S, Xing Z , et al. A ROR1-HER3-lncRNA signalling axis modulates the Hippo-YAP pathway to regulate bone metastasis[J]. Nat Cell Biol, 2017,19(2):106-119.
doi: 10.1038/ncb3464 pmid: 5336186
[33] Aoyama E, Kubota S, Khattab HM , et al. CCN2 enhances RANKL-induced osteoclast differentiation via direct binding to RANK and OPG[J]. Bone, 2015,73:242-248.
doi: 10.1016/j.bone.2014.12.058 pmid: 255545972
[34] Nishida T, Emura K, Kubota S , et al. CCN family 2/connective tissue growth factor (CCN2/CTGF) promotes osteoclastogenesis via induction of and interaction with dendritic cell-specific transmembrane protein (DC-STAMP)[J]. J Bone Miner Res, 2011,26(2):351-363.
doi: 10.1002/jbmr.222 pmid: 20721934
[35] Del Re DP, Matsuda T, Zhai P , et al. Proapoptotic Rassf1A/Mst1 signaling in cardiac fibroblasts is protective against pressure overload in mice[J]. J Clin Invest, 2010,120(10):3555-3567.
doi: 10.1172/JCI43569 pmid: 2947240
[36] Lock FE, Underhill-Day N, Dunwell T , et al. The RASSF8 candidate tumor suppressor inhibits cell growth and regulates the Wnt and NF-kappaB signaling pathways[J]. Oncogene, 2010,29(30):4307-4316.
doi: 10.1038/onc.2010.192 pmid: 20514026
[37] Song H, Kim H, Lee K , et al. Ablation of Rassf2 induces bone defects and subsequent haematopoietic anomalies in mice[J]. EMBO J, 2012,31(5):1147-1159.
doi: 10.1038/emboj.2011.480 pmid: 22227519
[38] Guo W, Keckesova Z, Donaher JL , et al. Slug and Sox9 cooperatively determine the mammary stem cell state[J]. Cell, 2012,148(5):1015-1028.
doi: 10.1016/j.cell.2012.02.008 pmid: 3305806
[39] Lin Y, Li XY, Willis AL , et al. Snail1-dependent control of embryonic stem cell pluripotency and lineage commitment[J]. Nat Commun, 2014,5:3070.
doi: 10.1038/ncomms4070 pmid: 24401905
[40] Tang Y, Weiss SJ . Snail/Slug-YAP/TAZ complexes cooperatively regulate mesenchymal stem cell function and bone formation[J]. Cell Cycle, 2017,16(5):399-405.
doi: 10.1080/15384101.2017.1280643 pmid: 28112996
[41] Tang Y, Feinberg T, Keller ET , et al. Snail/Slug binding interactions with YAP/TAZ control skeletal stem cell self-renewal and differentiation[J]. Nat Cell Biol, 2016,18(9):917-929.
doi: 10.1038/ncb3394 pmid: 27479603
[42] Jang EJ, Jeong H, Kang JO , et al. TM-25659 enhances osteogenic differentiation and suppresses adipogenic differentiation by modulating the transcriptional co-activator TAZ[J]. Br J Pharmacol, 2012,165(5):1584-1594.
doi: 10.1111/j.1476-5381.2011.01664.x pmid: 21913895
[43] Lin Z, Fateh A, Salem DM , et al. Periosteum: biology and applications in craniofacial bone regeneration[J]. J Dent Res, 2014,93(2):109-116.
doi: 10.1177/0022034513506445
[44] Wang C, Inzana JA, Mirando AJ , et al. NOTCH signaling in skeletal progenitors is critical for fracture re- pair[J]. J Clin Invest, 2016,126(4):1471-1481.
doi: 10.1172/JCI80672 pmid: 26950423
[45] Manderfield LJ, Aghajanian H, Engleka KA , et al. Hippo signaling is required for Notch-dependent smooth muscle differentiation of neural crest[J]. Development, 2015,142(17):2962-2971.
doi: 10.1242/dev.125807 pmid: 26253400
[46] Zanconato F, Forcato M, Battilana G , et al. Genome-wide association between YAP/TAZ/TEAD and AP-1 at enhancers drives oncogenic growth[J]. Nat Cell Biol, 2015,17(9):1218-1227.
doi: 10.1038/ncb3216 pmid: 26258633
[47] You B, Yang YL, Xu Z , et al. Inhibition of ERK1/2 down-regulates the Hippo/YAP signaling pathway in human NSCLC cells[J]. Oncotarget, 2015,6(6):4357-4368.
doi: 10.18632/oncotarget.2974 pmid: 4414195
[48] Wang DY, Wu YN, Huang JQ , et al. Hippo/YAP signaling pathway is involved in osteosarcoma chemoresistance[J]. Chin J Cancer, 2016,35:47.
doi: 10.1186/s40880-016-0109-z pmid: 4875723
[49] 朱忠胜, 张春林, 汪泱 . Hippo信号通路作用分子TAZ在人骨肉瘤及骨肉瘤干细胞中的表达[J]. 中国骨与关节杂志, 2014,3(2):130-134.
doi: 10.3969/j.issn.2095-252X.2014.02.012
Zhu ZS, Zhang CL, Wang Y . Expressions of effective molecules transcriptional coactivator with plasma dissociated zircon-binding motif of Hippo signaling pathway in human osteosarcomas and osteosarcoma stem cells[J]. Chin J Bone Tumor Bone Dis, 2014,3(2):130-134.
doi: 10.3969/j.issn.2095-252X.2014.02.012
[1] Zhu Xuanzhi,Zhao Lei. Research progress on the relationship between hypothyroidism and periodontitis [J]. Int J Stomatol, 2021, 48(4): 380-384.
[2] Sun Jianwei,Lei Lihong,Tan Jingyi,Chen Lili. Regulation of osteoimmunology by MicroRNA 155 and research progress of its possible mechanism in periodontitis [J]. Int J Stomatol, 2020, 47(5): 607-615.
[3] Wu Qi, Liu Chengcheng, Zheng Liwei, Li Jiyao, Zhou Xuedong, Xu Xin. Research progress on gut microbiota regulating bone metabolism [J]. Inter J Stomatol, 2017, 44(6): 628-635.
[4] Wu Yingying, Gong Ping.. Effect of insulin on bone metabolism around implant in diabetic rats [J]. Inter J Stomatol, 2017, 44(2): 183-188.
[5] Xu Xin, Wang Yanmin,Bai Ding. Silent mating type information regulation 2 homolog 1 in bone and cartilage homeostasis [J]. Inter J Stomatol, 2016, 43(5): 569-572.
[6] Yu Liming1, Shen Qingping1, Chen Jinkun2.. Adiponectin and their association with osteogenesis and bone metabolism [J]. Inter J Stomatol, 2015, 42(6): 681-684.
[7] Zou Huawei, Zhang Shiwen, Yuan Quan. Effect of chronic kidney disease on periodontal tissues [J]. Inter J Stomatol, 2014, 41(6): 730-734.
[8] Chen Mingyue1,2, Wang Changning1. Molecular mechanism of peroxisomal proliferator activated receptor γ regulation in periodontitis [J]. Inter J Stomatol, 2014, 41(5): 598-602.
[9] WANG Rui, WU Zhe.. Research progress on the use of simvastatin in bone metabolism [J]. Inter J Stomatol, 2011, 38(3): 335-338.
[10] MA Ting, ZHANG Jian. . Application of zoledronic acid locally applied affects bone metabolism in stomatology [J]. Inter J Stomatol, 2011, 38(3): 349-353.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
[1] . [J]. Foreign Med Sci: Stomatol, 1999, 26(06): .
[2] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[3] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[4] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[5] . [J]. Foreign Med Sci: Stomatol, 1999, 26(05): .
[6] . [J]. Foreign Med Sci: Stomatol, 1999, 26(04): .
[7] . [J]. Foreign Med Sci: Stomatol, 2005, 32(06): 458 -460 .
[8] . [J]. Foreign Med Sci: Stomatol, 2005, 32(06): 452 -454 .
[9] . [J]. Inter J Stomatol, 2008, 35(S1): .
[10] . [J]. Inter J Stomatol, 2008, 35(S1): .