HOXA10基因在骨发生和骨形成中作用的研究进展
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摘要
骨骼是人体的支架,保护机体的重要脏器,其发育和形成受到多种信号通路的调控。HOXA10作为同源异型盒基因(homeobox genes)的一员,参与了人体多个系统的生长发育过程,尤其是在骨发育和骨形成的过程中发挥着重要的调控作用。本文重点阐述HOXA10在骨骼发生和形成中的作用及其机制,以期为相关研究提供思路。
Bone is the scaffold of human body, and it plays an important role in protecting other organs. The development and formation of bone are regulated by multiple signaling pathways. As a member of homeobox genes, HOXA10 can participate in the development and growth of multiple systems by a variety of mechanisms, especially in the process of bone development and bone formation. In this review, we spotlight the role of HOXA10 in bone development and bone formation, expecting to provide novel ideas for the future studies.
Bone is the scaffold of human body, and it plays an important role in protecting other organs. The development and formation of bone are regulated by multiple signaling pathways. As a member of homeobox genes, HOXA10 can participate in the development and growth of multiple systems by a variety of mechanisms, especially in the process of bone development and bone formation. In this review, we spotlight the role of HOXA10 in bone development and bone formation, expecting to provide novel ideas for the future studies.
引文
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2张峻,张里程,唐佩福.骨改建中潜在的作用靶点-信号素Sema3A的研究进展[J].解放军医学院学报,2016,37(10):1100-1102.
3 Rutkovskiy A,Stenslokken KO,Vaage IJ.Osteoblast Differentiation at a Glance[J].Med Sci Monit Basic Res,2016,22:95-106.
4 Stein GS,Lian JB,van Wijnen AJ,et al.Runx2 control of organization,assembly and activity of the regulatory machinery for skeletal gene expression[J].Oncogene,2004,23(24):4315-4329.
5 Saurin AJ,Delfini MC,Maurel-Zaffran C,et al.The Generic Facet of Hox Protein Function:(Trends in Genetics 34,941-953,2018)[J/OL].https://linkinghub.elsevier.com/retrieve/pii/S0168-9525(18)30205-1.
6 Quinonez SC,Innis JW.Human HOX gene disorders[J].Mol Genet Metab,2014,111(1):4-15.
7 Bhatlekar S,Fields JZ,Boman BM.Role of HOX Genes in Stem Cell Differentiation and Cancer[J/OL].https://www.hindawi.com/journals/sci/2018/3569493.
8 Burglin TR.Homeodomain subtypes and functional diversity[J].Subcell Biochem,2011,52:95-122.
9 Benson GV,Nguyen TH,Maas RL.The expression pattern of the murine Hoxa-10 gene and the sequence recognition of its homeodomain reveal specific properties of Abdominal B-like genes[J].Mol Cell Biol,1995,15(3):1591-1601.
10 Botti G,De Chiara A,Di Bonito M,et al.Noncoding RNAs within the HOX gene network in tumor pathogenesis and progression[J].JCell Physiol,2018,234(1):395-413.
11 Apiou F,Flagiello D,Cillo C,et al.Fine mapping of human HOX gene clusters[J].Cytogenet Cell Genet,1996,73(1-2):114-115.
12 Hassan MQ,Tare R,Lee SH,et al.HOXA10 controls osteoblastogenesis by directly activating bone regulatory and phenotypic genes[J].Mol Cell Biol,2007,27(9):3337-3352.
13 Satokata I,Benson G,Maas R.Sexually dimorphic sterility phenotypes in Hoxa10-deficient mice[J].Nature,1995,374(6521):460-463.
14 Shao M,Yang Q,Zhu W,et al.LncHOXA10 drives liver TICs self-renewal and tumorigenesis via HOXA10 transcription activation[J].Mol Cancer,2018,17(1):173.
15 Zhou H,Cui X,Yuan H,et al.Effects of distinct drugs on gene transcription in an osteosarcoma cell line[J].Oncol Lett,2017,14(4):4694-4700.
16 Shao L,Chen Z,Peng D,et al.Methylation of the HOXA10Promoter Directs miR-196b-5p-Dependent Cell Proliferation and Invasion of Gastric Cancer Cells[J].Mol Cancer Res,2018,16(4):696-706.
17 Johansen S,Brenner AK,Bartaula-Brevik S,et al.The Possible Importance of beta3 Integrins for Leukemogenesis and Chemoresistance in Acute Myeloid Leukemia[J].Int J Mol Sci,2018,19(1):E25.
18刘忠厚.骨内科学[M].北京:化学工业出版社,2015:2.
19 Carapuco M,Novoa A,Bobola N,et al.Hox genes specify vertebral types in the presomitic mesoderm[J].Genes Dev,2005,19(18):2116-2121.
20 Wellik DM,Capecchi MR.Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton[J].Science,2003,301(5631):363-367.
21 Vinagre T,Moncaut N,Carapuco M,et al.Evidence for a myotomal Hox/Myf cascade governing nonautonomous control of rib specification within global vertebral domains[J].Dev Cell,2010,18(4):655-661.
22 Fendri K,Patten SA,Kaufman GN,et al.Microarray expression profiling identifies genes with altered expression in Adolescent Idiopathic Scoliosis[J].Eur Spine J,2013,22(6):1300-1311.
23 Yu E,Koffer PP,DiPetrillo TA,et al.Incidence,Treatment,and Survival Patterns for Sacral Chordoma in the United States,1974-2011[J].Front Oncol,2016,6:203.
24 Jager D,Barth TFE,Bruderlein S,et al.HOXA7,HOXA9,and HOXA10 are differentially expressed in clival and sacral chordomas[J].Sci Rep,2017,7(1):2032.
25 Rux DR,Wellik DM.Hox genes in the adult skeleton:Novel functions beyond embryonic development[J].Dev Dyn,2017,246(4):310-317.
26 Favier B,Rijli FM,Fromental-Ramain C,et al.Functional cooperation between the non-paralogous genes Hoxa-10 and Hoxd-11 in the developing forelimb and axial skeleton[J].Development,1996,122(2):449-460.
27 Wahba GM,Hostikka SL,Carpenter EM.The paralogous Hox genes Hoxa10 and Hoxd10 interact to pattern the mouse hindlimb peripheral nervous system and skeleton[J].Dev Biol,2001,231(1):87-102.
28尹鹏滨,唐佩福,张里程,等.信号素3A在骨自稳态与骨重塑中的作用[J].解放军医学院学报,2014,35(12):1272-1274.
29 Bruderer M,Richards RG,Alini M,et al.Role and regulation of RUNX2 in osteogenesis[J].Eur Cell Mater,2014,28:269-286.
30 Qin YX,Hu M.Mechanotransduction in musculoskeletal tissue regeneration:effects of fluid flow,loading,and cellularmolecular pathways[J/OL].https://www.hindawi.com/journals/bmri/2014/863421.
31 Chang CP,Brocchieri L,Shen WF,et al.Pbx modulation of Hox homeodomain amino-terminal arms establishes different DNA-binding specificities across the Hox locus[J].Mol Cell Biol,1996,16(4):1734-1745.
32 Gordon JA,Hassan MQ,Saini S,et al.Pbx1 represses osteoblastogenesis by blocking Hoxa10-mediated recruitment of chromatin remodeling factors[J].Mol Cell Biol,2010,30(14):3531-3541.
33 Gordon JA,Hassan MQ,Koss M,et al.Epigenetic regulation of early osteogenesis and mineralized tissue formation by a HOXA10-PBX1-associated complex[J].Cells Tissues Organs,2011,194(2-4):146-150.
34 Hassan MQ,Saini S,Gordon JA,et al.Molecular switches involving homeodomain proteins,HOXA10 and RUNX2 regulate osteoblastogenesis[J].Cells Tissues Organs,2009,189(1-4):122-125.
35 Hassan MQ,Tare RS,Lee SH,et al.BMP2 commitment to the osteogenic lineage involves activation of Runx2 by DLX3 and a homeodomain transcriptional network[J].J Biol Chem,2006,281(52):40515-40526.
36 Chen JR,Zhang J,Lazarenko OP,et al.Inhibition of fetal bone development through epigenetic down-regulation of HoxA10 in obese rats fed high-fat diet[J].Faseb j,2012,26(3):1131-1141.
37 Sollazzo V,Palmieri A,Pezzetti F,et al.Effects of pulsed electromagnetic fields on human osteoblastlike cells(MG-63):a pilot study[J].Clin Orthop Relat Res,2010,468(8):2260-2277.
38 Liao L,Yang X,Su X,et al.Redundant miR-3077-5p and miR-705 mediate the shift of mesenchymal stem cell lineage commitment to adipocyte in osteoporosis bone marrow[J].Cell Death Dis,2013,4:e600.
39 Huang J,Meng Y,Liu Y,et al.MicroRNA-320a Regulates the Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells by Targeting HOXA10[J].Cell Physiol Biochem,2016,38(1):40-48.
2张峻,张里程,唐佩福.骨改建中潜在的作用靶点-信号素Sema3A的研究进展[J].解放军医学院学报,2016,37(10):1100-1102.
3 Rutkovskiy A,Stenslokken KO,Vaage IJ.Osteoblast Differentiation at a Glance[J].Med Sci Monit Basic Res,2016,22:95-106.
4 Stein GS,Lian JB,van Wijnen AJ,et al.Runx2 control of organization,assembly and activity of the regulatory machinery for skeletal gene expression[J].Oncogene,2004,23(24):4315-4329.
5 Saurin AJ,Delfini MC,Maurel-Zaffran C,et al.The Generic Facet of Hox Protein Function:(Trends in Genetics 34,941-953,2018)[J/OL].https://linkinghub.elsevier.com/retrieve/pii/S0168-9525(18)30205-1.
6 Quinonez SC,Innis JW.Human HOX gene disorders[J].Mol Genet Metab,2014,111(1):4-15.
7 Bhatlekar S,Fields JZ,Boman BM.Role of HOX Genes in Stem Cell Differentiation and Cancer[J/OL].https://www.hindawi.com/journals/sci/2018/3569493.
8 Burglin TR.Homeodomain subtypes and functional diversity[J].Subcell Biochem,2011,52:95-122.
9 Benson GV,Nguyen TH,Maas RL.The expression pattern of the murine Hoxa-10 gene and the sequence recognition of its homeodomain reveal specific properties of Abdominal B-like genes[J].Mol Cell Biol,1995,15(3):1591-1601.
10 Botti G,De Chiara A,Di Bonito M,et al.Noncoding RNAs within the HOX gene network in tumor pathogenesis and progression[J].JCell Physiol,2018,234(1):395-413.
11 Apiou F,Flagiello D,Cillo C,et al.Fine mapping of human HOX gene clusters[J].Cytogenet Cell Genet,1996,73(1-2):114-115.
12 Hassan MQ,Tare R,Lee SH,et al.HOXA10 controls osteoblastogenesis by directly activating bone regulatory and phenotypic genes[J].Mol Cell Biol,2007,27(9):3337-3352.
13 Satokata I,Benson G,Maas R.Sexually dimorphic sterility phenotypes in Hoxa10-deficient mice[J].Nature,1995,374(6521):460-463.
14 Shao M,Yang Q,Zhu W,et al.LncHOXA10 drives liver TICs self-renewal and tumorigenesis via HOXA10 transcription activation[J].Mol Cancer,2018,17(1):173.
15 Zhou H,Cui X,Yuan H,et al.Effects of distinct drugs on gene transcription in an osteosarcoma cell line[J].Oncol Lett,2017,14(4):4694-4700.
16 Shao L,Chen Z,Peng D,et al.Methylation of the HOXA10Promoter Directs miR-196b-5p-Dependent Cell Proliferation and Invasion of Gastric Cancer Cells[J].Mol Cancer Res,2018,16(4):696-706.
17 Johansen S,Brenner AK,Bartaula-Brevik S,et al.The Possible Importance of beta3 Integrins for Leukemogenesis and Chemoresistance in Acute Myeloid Leukemia[J].Int J Mol Sci,2018,19(1):E25.
18刘忠厚.骨内科学[M].北京:化学工业出版社,2015:2.
19 Carapuco M,Novoa A,Bobola N,et al.Hox genes specify vertebral types in the presomitic mesoderm[J].Genes Dev,2005,19(18):2116-2121.
20 Wellik DM,Capecchi MR.Hox10 and Hox11 genes are required to globally pattern the mammalian skeleton[J].Science,2003,301(5631):363-367.
21 Vinagre T,Moncaut N,Carapuco M,et al.Evidence for a myotomal Hox/Myf cascade governing nonautonomous control of rib specification within global vertebral domains[J].Dev Cell,2010,18(4):655-661.
22 Fendri K,Patten SA,Kaufman GN,et al.Microarray expression profiling identifies genes with altered expression in Adolescent Idiopathic Scoliosis[J].Eur Spine J,2013,22(6):1300-1311.
23 Yu E,Koffer PP,DiPetrillo TA,et al.Incidence,Treatment,and Survival Patterns for Sacral Chordoma in the United States,1974-2011[J].Front Oncol,2016,6:203.
24 Jager D,Barth TFE,Bruderlein S,et al.HOXA7,HOXA9,and HOXA10 are differentially expressed in clival and sacral chordomas[J].Sci Rep,2017,7(1):2032.
25 Rux DR,Wellik DM.Hox genes in the adult skeleton:Novel functions beyond embryonic development[J].Dev Dyn,2017,246(4):310-317.
26 Favier B,Rijli FM,Fromental-Ramain C,et al.Functional cooperation between the non-paralogous genes Hoxa-10 and Hoxd-11 in the developing forelimb and axial skeleton[J].Development,1996,122(2):449-460.
27 Wahba GM,Hostikka SL,Carpenter EM.The paralogous Hox genes Hoxa10 and Hoxd10 interact to pattern the mouse hindlimb peripheral nervous system and skeleton[J].Dev Biol,2001,231(1):87-102.
28尹鹏滨,唐佩福,张里程,等.信号素3A在骨自稳态与骨重塑中的作用[J].解放军医学院学报,2014,35(12):1272-1274.
29 Bruderer M,Richards RG,Alini M,et al.Role and regulation of RUNX2 in osteogenesis[J].Eur Cell Mater,2014,28:269-286.
30 Qin YX,Hu M.Mechanotransduction in musculoskeletal tissue regeneration:effects of fluid flow,loading,and cellularmolecular pathways[J/OL].https://www.hindawi.com/journals/bmri/2014/863421.
31 Chang CP,Brocchieri L,Shen WF,et al.Pbx modulation of Hox homeodomain amino-terminal arms establishes different DNA-binding specificities across the Hox locus[J].Mol Cell Biol,1996,16(4):1734-1745.
32 Gordon JA,Hassan MQ,Saini S,et al.Pbx1 represses osteoblastogenesis by blocking Hoxa10-mediated recruitment of chromatin remodeling factors[J].Mol Cell Biol,2010,30(14):3531-3541.
33 Gordon JA,Hassan MQ,Koss M,et al.Epigenetic regulation of early osteogenesis and mineralized tissue formation by a HOXA10-PBX1-associated complex[J].Cells Tissues Organs,2011,194(2-4):146-150.
34 Hassan MQ,Saini S,Gordon JA,et al.Molecular switches involving homeodomain proteins,HOXA10 and RUNX2 regulate osteoblastogenesis[J].Cells Tissues Organs,2009,189(1-4):122-125.
35 Hassan MQ,Tare RS,Lee SH,et al.BMP2 commitment to the osteogenic lineage involves activation of Runx2 by DLX3 and a homeodomain transcriptional network[J].J Biol Chem,2006,281(52):40515-40526.
36 Chen JR,Zhang J,Lazarenko OP,et al.Inhibition of fetal bone development through epigenetic down-regulation of HoxA10 in obese rats fed high-fat diet[J].Faseb j,2012,26(3):1131-1141.
37 Sollazzo V,Palmieri A,Pezzetti F,et al.Effects of pulsed electromagnetic fields on human osteoblastlike cells(MG-63):a pilot study[J].Clin Orthop Relat Res,2010,468(8):2260-2277.
38 Liao L,Yang X,Su X,et al.Redundant miR-3077-5p and miR-705 mediate the shift of mesenchymal stem cell lineage commitment to adipocyte in osteoporosis bone marrow[J].Cell Death Dis,2013,4:e600.
39 Huang J,Meng Y,Liu Y,et al.MicroRNA-320a Regulates the Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells by Targeting HOXA10[J].Cell Physiol Biochem,2016,38(1):40-48.