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Osteoporosis International

Erschienen in:

07.09.2018 | Review Article

Notch in skeletal physiology and disease

verfasst von: E. Canalis

Erschienen in: Osteoporosis International | Ausgabe 12/2018

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Abstract

Notch (Notch1 through 4) are transmembrane receptors that play a fundamental role in cell differentiation and function. Notch receptors are activated following interactions with their ligands in neighboring cells. There are five classic ligands termed Jagged (Jag)1 and Jag2 and Delta-like (Dll)1, Dll3, and Dll4. Recent work has established Notch as a signaling pathway that plays a critical role in the differentiation and function of cells of the osteoblast and osteoclast lineages and in skeletal development and bone remodeling. The effects of Notch are cell-context dependent, and the four Notch receptors carry out specific functions in the skeleton. Gain- and loss-of-function mutations of components of the Notch signaling pathway result in a variety of congenital disorders with significant craniofacial and skeletal manifestations. The Notch ligand Jag1 is a determinant of bone mineral density, and Notch plays a role in the early phases of fracture healing. Alterations in Notch signaling are associated with osteosarcoma and with the metastatic potential of carcinoma of the breast and of the prostate. Controlling Notch signaling could prove useful in diseases of Notch gain-of-function and in selected skeletal disorders. However, clinical data on agents that modify Notch signaling are not available. In conclusion, Notch signaling is a novel pathway that regulates skeletal homeostasis in health and disease.

Bai S, Kopan R, Zou W, Hilton MJ, Ong CT, Long F, Ross FP, Teitelbaum SL (2008) NOTCH1 regulates osteoclastogenesis directly in osteoclast precursors and indirectly via osteoblast lineage cells. J Biol Chem 283:6509–6518PubMed

Engin F, Yao Z, Yang T, Zhou G, Bertin T, Jiang MM, Chen Y, Wang L, Zheng H, Sutton RE, Boyce BF, Lee B (2008) Dimorphic effects of Notch signaling in bone homeostasis. Nat Med 14:299–305PubMedPubMedCentral

Fukushima H, Nakao A, Okamoto F, Shin M, Kajiya H, Sakano S, Bigas A, Jimi E, Okabe K (2008) The association of Notch2 and NF-kappaB accelerates RANKL-induced osteoclastogenesis. Mol Cell Biol 28:6402–6412PubMedPubMedCentral

Hilton MJ, Tu X, Wu X, Bai S, Zhao H, Kobayashi T, Kronenberg HM, Teitelbaum SL, Ross FP, Kopan R, Long F (2008) Notch signaling maintains bone marrow mesenchymal progenitors by suppressing osteoblast differentiation. Nat Med 14:306–314PubMedPubMedCentral

Zanotti S, Canalis E (2016) Notch signaling and the skeleton. Endocr Rev 37:223–253PubMedPubMedCentral

Canalis E, Adams DJ, Boskey A, Parker K, Kranz L, Zanotti S (2013) Notch signaling in osteocytes differentially regulates cancellous and cortical bone remodeling. J Biol Chem 288:25614–25625PubMedPubMedCentral

Canalis E, Parker K, Feng JQ, Zanotti S (2013) Osteoblast lineage-specific effects of Notch activation in the skeleton. Endocrinology 154:623–634PubMed

Sanchez-Irizarry C, Carpenter AC, Weng AP, Pear WS, Aster JC, Blacklow SC (2004) Notch subunit heterodimerization and prevention of ligand-independent proteolytic activation depend, respectively, on a novel domain and the LNR repeats. Mol Cell Biol 24:9265–9273PubMedPubMedCentral

Kopan R, Ilagan MX (2009) The canonical Notch signaling pathway: unfolding the activation mechanism. Cell 137:216–233PubMedPubMedCentral

10.

Siebel C, Lendahl U (2017) Notch signaling in development, tissue homeostasis, and disease. Physiol Rev 97:1235–1294PubMed

11.

Iso T, Kedes L, Hamamori Y (2003) HES and HERP families: multiple effectors of the Notch signaling pathway. J Cell Physiol 194:237–255PubMed

12.

Kovall RA (2007) Structures of CSL, Notch and Mastermind proteins: piecing together an active transcription complex. Curr Opin Struct Biol 17:117–127PubMed

13.

Wu J, Bresnick EH (2007) Bare rudiments of notch signaling: how receptor levels are regulated. Trends Biochem Sci 32:477–485PubMed

14.

Yuan Z, Friedmann DR, Vanderwielen BD, Collins KJ, Kovall RA (2012) Characterization of CSL (CBF-1, Su(H), Lag-1) mutants reveals differences in signaling mediated by Notch1 and Notch2. J Biol Chem 287:34904–34916PubMedPubMedCentral

15.

Zanotti S, Canalis E (2017) Parathyroid hormone inhibits Notch signaling in osteoblasts and osteocytes. Bone 103:159–167PubMedPubMedCentral

16.

Deregowski V, Gazzerro E, Priest L, Rydziel S, Canalis E (2006) Notch 1 overexpression inhibits osteoblastogenesis by suppressing Wnt/beta-catenin but not bone morphogenetic protein signaling. J Biol Chem 281:6203–6210PubMed

17.

Zanotti S, Canalis E (2014) Notch1 and Notch2 expression in osteoblast precursors regulates femoral microarchitecture. Bone 62:22–28PubMedPubMedCentral

18.

Canalis E, Bridgewater D, Schilling L, Zanotti S (2015) Canonical Notch activation in osteocytes causes osteopetrosis. Am J Phys Endocrinol Metab 310:E171–E182

19.

Tu X, Delgado-Calle J, Condon KW, Maycas M, Zhang H, Carlesso N, Taketo MM, Burr DB, Plotkin LI, Bellido T (2015) Osteocytes mediate the anabolic actions of canonical Wnt/beta-catenin signaling in bone. Proc Natl Acad Sci U S A 112:E478–E486PubMedPubMedCentral

20.

Robling AG, Niziolek PJ, Baldridge LA, Condon KW, Allen MR, Alam I, Mantila SM, Gluhak-Heinrich J, Bellido TM, Harris SE, Turner CH (2008) Mechanical stimulation of bone in vivo reduces osteocyte expression of Sost/sclerostin. J Biol Chem 283:5866–5875PubMed

21.

Yamada T, Yamazaki H, Yamane T, Yoshino M, Okuyama H, Tsuneto M, Kurino T, Hayashi S, Sakano S (2003) Regulation of osteoclast development by Notch signaling directed to osteoclast precursors and through stromal cells. Blood 101:2227–2234PubMed

22.

Zhao B, Grimes SN, Li S, Hu X, Ivashkiv LB (2012) TNF-induced osteoclastogenesis and inflammatory bone resorption are inhibited by transcription factor RBP-J. J Exp Med 209:319–334PubMedPubMedCentral

23.

Canalis E, Schilling L, Yee SP, Lee SK, Zanotti S (2016) Hajdu Cheney mouse mutants exhibit osteopenia, increased osteoclastogenesis and bone resorption. J Biol Chem 291:1538–1551PubMed

24.

Canalis E, Zanotti S (2017) Hairy and enhancer of split-related with YRPW motif-like (HeyL) is dispensable for bone remodeling in mice. J Cell Biochem 118:1819–1826PubMedPubMedCentral

25.

Salie R, Kneissel M, Vukevic M, Zamurovic N, Kramer I, Evans G, Gerwin N, Mueller M, Kinzel B, Susa M (2010) Ubiquitous overexpression of Hey1 transcription factor leads to osteopenia and chondrocyte hypertrophy in bone. Bone 46:680–694PubMed

26.

Zanotti S, Canalis E (2013) Hairy and enhancer of split-related with YRPW motif (HEY)2 regulates bone remodeling in mice. J Biol Chem 288:21547–21557PubMedPubMedCentral

27.

Zanotti S, Smerdel-Ramoya A, Canalis E (2011) Hairy and enhancer of split (HES)1 is a determinant of bone mass. J Biol Chem 286:2648–2657PubMed

28.

Calvi LM, Adams GB, Weibrecht KW, Weber JM, Olson DP, Knight MC, Martin RP, Schipani E, Divieti P, Bringhurst FR, Milner LA, Kronenberg HM, Scadden DT (2003) Osteoblastic cells regulate the haematopoietic stem cell niche. Nature 425:841–846PubMed

29.

Duggan SP, McCarthy JV (2016) Beyond gamma-secretase activity: the multifunctional nature of presenilins in cell signalling pathways. Cell Signal 28:1–11PubMed

30.

del Alamo D, Rouault H, Schweisguth F (2011) Mechanism and significance of cis-inhibition in Notch signalling. Curr Biol 21:R40–R47PubMed

31.

Zanotti S, Yu J, Adhikari S, Canalis E (2018) Glucocorticoids inhibit notch target gene expression in osteoblasts. J Cell Biochem 119:6016–6023PubMedPubMedCentral

32.

Canalis E (2018) Clinical and experimental aspects of notch receptor signaling: Hajdu-Cheney syndrome and related disorders. Metabolism 80:48–56PubMed

33.

Isidor B, Lindenbaum P, Pichon O, Bézieau S, Dina C, Jacquemont S, Martin-Coignard D, Thauvin-Robinet C, le Merrer M, Mandel JL, David A, Faivre L, Cormier-Daire V, Redon R, le Caignec C (2011) Truncating mutations in the last exon of NOTCH2 cause a rare skeletal disorder with osteoporosis. Nat Genet 43:306–308PubMed

34.

Simpson MA, Irving MD, Asilmaz E, Gray MJ, Dafou D, Elmslie FV, Mansour S, Holder SE, Brain CE, Burton BK, Kim KH, Pauli RM, Aftimos S, Stewart H, Kim CA, Holder-Espinasse M, Robertson SP, Drake WM, Trembath RC (2011) Mutations in NOTCH2 cause Hajdu-Cheney syndrome, a disorder of severe and progressive bone loss. Nat Genet 43:303–305PubMed

35.

Zhao W, Petit E, Gafni RI, Collins MT, Robey PG, Seton M, Miller KK, Mannstadt M (2013) Mutations in NOTCH2 in patients with Hajdu-Cheney syndrome. Osteoporos Int 24:2275–2281PubMedPubMedCentral

36.

Lehman RA, Stears JC, Wesenberg RL, Nusbaum ED (1977) Familial osteosclerosis with abnormalities of the nervous system and meninges. J Pediatr 90:49–54PubMed

37.

Gripp KW, Robbins KM, Sobreira NL et al (2015) Truncating mutations in the last exon of NOTCH3 cause lateral meningocele syndrome. Am J Med Genet A 167A:271–281PubMed

38.

Temtamy SA, Aglan MS (2008) Brachydactyly. Orphanet J Rare Dis 3:15PubMedPubMedCentral

39.

Tian J, Ling L, Shboul M, Lee H, O'Connor B, Merriman B, Nelson SF, Cool S, Ababneh OH, al-Hadidy A, Masri A, Hamamy H, Reversade B (2010) Loss of CHSY1, a secreted FRINGE enzyme, causes syndromic brachydactyly in humans via increased NOTCH signaling. Am J Hum Genet 87:768–778PubMedPubMedCentral

40.

Stittrich AB, Lehman A, Bodian DL, Ashworth J, Zong Z, Li H, Lam P, Khromykh A, Iyer RK, Vockley JG, Baveja R, Silva ES, Dixon J, Leon EL, Solomon BD, Glusman G, Niederhuber JE, Roach JC, Patel MS (2014) Mutations in NOTCH1 cause Adams-Oliver syndrome. Am J Hum Genet 95:275–284PubMedPubMedCentral

41.

Hassed SJ, Wiley GB, Wang S, Lee JY, Li S, Xu W, Zhao ZJ, Mulvihill JJ, Robertson J, Warner J, Gaffney PM (2012) RBPJ mutations identified in two families affected by Adams-Oliver syndrome. Am J Hum Genet 91:391–395PubMedPubMedCentral

42.

Meester JA, Southgate L, Stittrich AB et al (2015) Heterozygous loss-of-function mutations in DLL4 cause Adams-Oliver syndrome. Am J Hum Genet 97:475–482PubMedPubMedCentral

43.

Shaheen R, Aglan M, Keppler-Noreuil K, Faqeih E, Ansari S, Horton K, Ashour A, Zaki MS, al-Zahrani F, Cueto-González AM, Abdel-Salam G, Temtamy S, Alkuraya FS (2013) Mutations in EOGT confirm the genetic heterogeneity of autosomal-recessive Adams-Oliver syndrome. Am J Hum Genet 92:598–604PubMedPubMedCentral

44.

Emerick KM, Rand EB, Goldmuntz E, Krantz ID, Spinner NB, Piccoli DA (1999) Features of Alagille syndrome in 92 patients: frequency and relation to prognosis. Hepatology 29:822–829PubMed

45.

Crosnier C, Driancourt C, Raynaud N, Dhorne-Pollet S, Pollet N, Bernard O, Hadchouel M, Meunier-Rotival M (1999) Mutations in JAGGED1 gene are predominantly sporadic in Alagille syndrome. Gastroenterology 116:1141–1148PubMed

46.

Kamath BM, Bauer RC, Loomes KM, Chao G, Gerfen J, Hutchinson A, Hardikar W, Hirschfield G, Jara P, Krantz ID, Lapunzina P, Leonard L, Ling S, Ng VL, Hoang PL, Piccoli DA, Spinner NB (2012) NOTCH2 mutations in Alagille syndrome. J Med Genet 49:138–144PubMed

47.

McDaniell R, Warthen DM, Sanchez-Lara PA, Pai A, Krantz ID, Piccoli DA, Spinner NB (2006) NOTCH2 mutations cause Alagille syndrome, a heterogeneous disorder of the notch signaling pathway. Am J Hum Genet 79:169–173PubMedPubMedCentral

48.

Dunwoodie SL, Clements M, Sparrow DB, Sa X, Conlon RA, Beddington RS (2002) Axial skeletal defects caused by mutation in the spondylocostal dysplasia/pudgy gene Dll3 are associated with disruption of the segmentation clock within the presomitic mesoderm. Development 129:1795–1806PubMed

49.

Cornier AS, Staehling-Hampton K, Delventhal KM, Saga Y, Caubet JF, Sasaki N, Ellard S, Young E, Ramirez N, Carlo SE, Torres J, Emans JB, Turnpenny PD, Pourquié O (2008) Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome. Am J Hum Genet 82:1334–1341PubMedPubMedCentral

50.

Sparrow DB, Chapman G, Wouters MA, Whittock NV, Ellard S, Fatkin D, Turnpenny PD, Kusumi K, Sillence D, Dunwoodie SL (2006) Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype. Am J Hum Genet 78:28–37PubMed

51.

Sparrow DB, Guillen-Navarro E, Fatkin D, Dunwoodie SL (2008) Mutation of hairy-and-enhancer-of-Split-7 in humans causes spondylocostal dysostosis. Hum Mol Genet 17:3761–3766PubMed

52.

Descartes M, Rojnueangnit K, Cole L, Sutton A, Morgan SL, Patry L, Samuels ME (2014) Hajdu-Cheney syndrome: phenotypical progression with de-novo NOTCH2 mutation. Clin Dysmorphol 23:88–94PubMed

53.

Hajdu N, Kauntze R (1948) Cranio-skeletal dysplasia. Br J Radiol 21:42–48PubMed

54.

Sargin G, Cildag S, Senturk T (2013) Hajdu-Cheney syndrome with ventricular septal defect. Kaohsiung J Med Sci 29:343–344PubMed

55.

Sakka S, Gafni RI, Davies JH, Clarke B, Tebben P, Samuels M, Saraff V, Klaushofer K, Fratzl-Zelman N, Roschger P, Rauch F, Högler W (2017) Bone structural characteristics and response to bisphosphonate treatment in children with Hajdu-Cheney syndrome. J Clin Endocrinol Metab 102:4163–4172PubMedPubMedCentral

56.

Vollersen N, Hermans-Borgmeyer I, Cornils K, Fehse B, Rolvien T, Triviai I, Jeschke A, Oheim R, Amling M, Schinke T, Yorgan TA (2018) High bone turnover in mice carrying a pathogenic Notch2 mutation causing Hajdu-Cheney syndrome. J Bone Miner Res 33:70–83PubMed

57.

Zanotti S, Yu J, Bridgewater D, Wolf JM, Canalis E (2018) Mice harboring a Hajdu Cheney syndrome mutation are sensitized to osteoarthritis. Bone 114:198–205PubMedPubMedCentral

58.

Galli-Tsinopoulou A, Kyrgios I, Giza S, Giannopoulou EM, Maggana I, Laliotis N (2012) Two-year cyclic infusion of pamidronate improves bone mass density and eliminates risk of fractures in a girl with osteoporosis due to Hajdu-Cheney syndrome. Minerva Endocrinol 37:283–289PubMed

59.

McKiernan FE (2008) Integrated anti-remodeling and anabolic therapy for the osteoporosis of Hajdu-Cheney syndrome: 2-year follow-up. Osteoporos Int 19:379–380PubMed

60.

Adami G, Rossini M, Gatti D, Orsolini G, Idolazzi L, Viapiana O, Scarpa A, Canalis E (2016) Hajdu Cheney syndrome; report of a novel NOTCH2 mutation and treatment with denosumab. Bone 92:150–156PubMed

61.

Engin F, Bertin T, Ma O, Jiang MM, Wang L, Sutton RE, Donehower LA, Lee B (2009) Notch signaling contributes to the pathogenesis of human osteosarcomas. Hum Mol Genet 18:1464–1470PubMedPubMedCentral

62.

Tao J, Jiang MM, Jiang L, Salvo JS, Zeng HC, Dawson B, Bertin TK, Rao PH, Chen R, Donehower LA, Gannon F, Lee BH (2014) Notch activation as a driver of osteogenic sarcoma. Cancer Cell 26:390–401PubMedPubMedCentral

63.

Canalis E, Sanjay A, Yu J, Zanotti S (2017) An antibody to Notch2 reverses the osteopenic phenotype of Hajdu-Cheney mutant male mice. Endocrinology 158:730–742PubMedPubMedCentral

64.

Wu Y, Cain-Hom C, Choy L, Hagenbeek TJ, de Leon GP, Chen Y, Finkle D, Venook R, Wu X, Ridgway J, Schahin-Reed D, Dow GJ, Shelton A, Stawicki S, Watts RJ, Zhang J, Choy R, Howard P, Kadyk L, Yan M, Zha J, Callahan CA, Hymowitz SG, Siebel CW (2010) Therapeutic antibody targeting of individual Notch receptors. Nature 464:1052–1057PubMed

65.

Kiel MJ, Velusamy T, Betz BL, Zhao L, Weigelin HG, Chiang MY, Huebner-Chan DR, Bailey NG, Yang DT, Bhagat G, Miranda RN, Bahler DW, Medeiros LJ, Lim MS, Elenitoba-Johnson KSJ (2012) Whole-genome sequencing identifies recurrent somatic NOTCH2 mutations in splenic marginal zone lymphoma. J Exp Med 209:1553–1565PubMedPubMedCentral

66.

Yu J, Zanotti S, Schilling L, Schoenherr C, Economides AN, Sanjay A, Canalis E (2018) Induction of the Hajdu-Cheney syndrome mutation in CD19 B cells in mice alters B-cell allocation but not skeletal homeostasis. Am J Pathol 188:1430–1446PubMedPubMedCentral

67.

Yu J, Zanotti S, Walia B, Jellison E, Sanjay A, Canalis E (2018) The Hajdu Cheney mutation is a determinant of B-cell allocation of the splenic marginal zone. Am J Pathol 188:149–159PubMedPubMedCentral

68.

Gripp KW, Scott CI Jr, Hughes HE et al (1997) Lateral meningocele syndrome: three new patients and review of the literature. Am J Med Genet 70:229–239PubMed

69.

Gripp KW (2011) Lateral meningocele syndrome and Hajdu-Cheney syndrome: different disorders with overlapping phenotypes. Am J Med Genet A 155A:1773–1774 author reply 1775PubMed

70.

Snape KM, Ruddy D, Zenker M, Wuyts W, Whiteford M, Johnson D, Lam W, Trembath RC (2009) The spectra of clinical phenotypes in aplasia cutis congenita and terminal transverse limb defects. Am J Med Genet A 149A:1860–1881PubMed

71.

Hoyme HE, Jones KL, Van Allen MI, Saunders BS, Benirschke K (1982) Vascular pathogenesis of transverse limb reduction defects. J Pediatr 101:839–843PubMed

72.

Alagille D, Estrada A, Hadchouel M, Gautier M, Odievre M, Dommergues JP (1987) Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases. J Pediatr 110:195–200PubMed

73.

Morrissette JD, Colliton RP, Spinner NB (2001) Defective intracellular transport and processing of JAG1 missense mutations in Alagille syndrome. Hum Mol Genet 10:405–413PubMed

74.

Boyer-Di Ponio J, Wright-Crosnier C, Groyer-Picard MT, Driancourt C, Beau I, Hadchouel M, Meunier-Rotival M (2007) Biological function of mutant forms of JAGGED1 proteins in Alagille syndrome: inhibitory effect on Notch signaling. Hum Mol Genet 16:2683–2692PubMed

75.

Xue Y, Gao X, Lindsell CE, Norton CR, Chang B, Hicks C, Gendron-Maguire M, Rand EB, Weinmaster G, Gridley T (1999) Embryonic lethality and vascular defects in mice lacking the Notch ligand Jagged1. Hum Mol Genet 8:723–730PubMed

76.

McCright B, Gao X, Shen L, Lozier J, Lan Y, Maguire M, Herzlinger D, Weinmaster G, Jiang R, Gridley T (2001) Defects in development of the kidney, heart and eye vasculature in mice homozygous for a hypomorphic Notch2 mutation. Development 128:491–502PubMed

77.

Turnpenny PD, Whittock N, Duncan J, Dunwoodie S, Kusumi K, Ellard S (2003) Novel mutations in DLL3, a somitogenesis gene encoding a ligand for the Notch signalling pathway, cause a consistent pattern of abnormal vertebral segmentation in spondylocostal dysostosis. J Med Genet 40:333–339PubMedPubMedCentral

78.

Kusumi K, Sun ES, Kerrebrock AW, Bronson RT, Chi DC, Bulotsky MS, Spencer JB, Birren BW, Frankel WN, Lander ES (1998) The mouse pudgy mutation disrupts Delta homologue Dll3 and initiation of early somite boundaries. Nat Genet 19:274–278PubMed

79.

Saga Y, Hata N, Koseki H, Taketo MM (1997) Mesp2: a novel mouse gene expressed in the presegmented mesoderm and essential for segmentation initiation. Genes Dev 11:1827–1839PubMed

80.

Kung AW, Xiao SM, Cherny S et al (2010) Association of JAG1 with bone mineral density and osteoporotic fractures: a genome-wide association study and follow-up replication studies. Am J Hum Genet 86:229–239PubMedPubMedCentral

81.

Dishowitz MI, Terkhorn SP, Bostic SA, Hankenson KD (2012) Notch signaling components are upregulated during both endochondral and intramembranous bone regeneration. J Orthop Res 30:296–303PubMed

82.

Wang C, Shen J, Yukata K, Inzana JA, O'Keefe RJ, Awad HA, Hilton MJ (2015) Transient gamma-secretase inhibition accelerates and enhances fracture repair likely via Notch signaling modulation. Bone 73:77–89PubMed

83.

Wang C, Inzana JA, Mirando AJ, Ren Y, Liu Z, Shen J, O'Keefe RJ, Awad HA, Hilton MJ (2016) NOTCH signaling in skeletal progenitors is critical for fracture repair. J Clin Invest 126:1471–1481PubMedPubMedCentral

84.

Maes C, Kobayashi T, Selig MK, Torrekens S, Roth SI, Mackem S, Carmeliet G, Kronenberg HM (2010) Osteoblast precursors, but not mature osteoblasts, move into developing and fractured bones along with invading blood vessels. Dev Cell 19:329–344PubMedPubMedCentral

85.

Ramasamy SK, Kusumbe AP, Wang L, Adams RH (2014) Endothelial Notch activity promotes angiogenesis and osteogenesis in bone. Nature 507:376–380PubMedPubMedCentral

86.

Dishowitz MI, Mutyaba PL, Takacs JD, Barr AM, Engiles JB, Ahn J, Hankenson KD (2013) Systemic inhibition of canonical Notch signaling results in sustained callus inflammation and alters multiple phases of fracture healing. PLoS One 8:e68726PubMedPubMedCentral

87.

Tanaka M, Setoguchi T, Hirotsu M, Gao H, Sasaki H, Matsunoshita Y, Komiya S (2009) Inhibition of Notch pathway prevents osteosarcoma growth by cell cycle regulation. Br J Cancer 100:1957–1965PubMedPubMedCentral

88.

Dailey DD, Anfinsen KP, Pfaff LE, Ehrhart EJ, Charles JB, Bonsdorff TB, Thamm DH, Powers BE, Jonasdottir TJ, Duval DL (2013) HES1, a target of Notch signaling, is elevated in canine osteosarcoma, but reduced in the most aggressive tumors. BMC Vet Res 9:130PubMedPubMedCentral

89.

Hughes DP (2009) How the NOTCH pathway contributes to the ability of osteosarcoma cells to metastasize. Cancer Treat Res 152:479–496PubMed

90.

Zhang Z, Wang H, Ikeda S, Fahey F, Bielenberg D, Smits P, Hauschka PV (2010) Notch3 in human breast cancer cell lines regulates osteoblast-cancer cell interactions and osteolytic bone metastasis. Am J Pathol 177:1459–1469PubMedPubMedCentral

91.

Sethi N, Dai X, Winter CG, Kang Y (2011) Tumor-derived JAGGED1 promotes osteolytic bone metastasis of breast cancer by engaging notch signaling in bone cells. Cancer Cell 19:192–205PubMedPubMedCentral

92.

Zayzafoon M, Abdulkadir SA, McDonald JM (2004) Notch signaling and ERK activation are important for the osteomimetic properties of prostate cancer bone metastatic cell lines. J Biol Chem 279:3662–3670PubMed

93.

Ryeom SW (2011) The cautionary tale of side effects of chronic Notch1 inhibition. J Clin Invest 121:508–509PubMedPubMedCentral

94.

De Strooper B, Annaert W, Cupers P et al (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398:518–522PubMed

95.

Ilagan MX, Kopan R (2013) Selective blockade of transport via SERCA inhibition: the answer for oncogenic forms of Notch? Cancer Cell 23:267–269PubMed

96.

Moellering RE, Cornejo M, Davis TN, Del BC, Aster JC, Blacklow SC, Kung AL, Gilliland DG, Verdine GL, Bradner JE (2009) Direct inhibition of the NOTCH transcription factor complex. Nature 462:182–188PubMedPubMedCentral

97.

Li K, Li Y, Wu W, Gordon WR, Chang DW, Lu M, Scoggin S, Fu T, Vien L, Histen G, Zheng J, Martin-Hollister R, Duensing T, Singh S, Blacklow SC, Yao Z, Aster JC, Zhou BBS (2008) Modulation of Notch signaling by antibodies specific for the extracellular negative regulatory region of NOTCH3. J Biol Chem 283:8046–8054PubMed

98.

Zanotti S, Canalis E (2010) Notch and the skeleton. Mol Cell Biol 30:886–896PubMed

99.

Aste-Amezaga M, Zhang N, Lineberger JE et al (2010) Characterization of Notch1 antibodies that inhibit signaling of both normal and mutated Notch1 receptors. PLoS One 5:e9094PubMedPubMedCentral

100.

Yan M, Callahan CA, Beyer JC, Allamneni KP, Zhang G, Ridgway JB, Niessen K, Plowman GD (2010) Chronic DLL4 blockade induces vascular neoplasms. Nature 463:E6–E7PubMed

Titel: Notch in skeletal physiology and disease
verfasst von: E. Canalis
Publikationsdatum: 07.09.2018
Verlag: Springer London
Erschienen in: Osteoporosis International / Ausgabe 12/2018
Print ISSN: 0937-941X
Elektronische ISSN: 1433-2965
DOI: https://doi.org/10.1007/s00198-018-4694-3

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