WNT Signaling and Bone: Lessons From Skeletal Dysplasias and Disorders.
Wingless and Int-1 (WNT)/planar cell polarity (PCP) pathway
Wingless and int-1 (WNT)/Ca2+ pathway
Wingless and int-1 (WNT)/β-catenin pathway
osteoporosis
skeletal dysplasias
Journal
Frontiers in endocrinology
ISSN: 1664-2392
Titre abrégé: Front Endocrinol (Lausanne)
Pays: Switzerland
ID NLM: 101555782
Informations de publication
Date de publication:
2020
2020
Historique:
received:
20
12
2019
accepted:
09
03
2020
entrez:
25
4
2020
pubmed:
25
4
2020
medline:
30
3
2021
Statut:
epublish
Résumé
Skeletal dysplasias are a diverse group of heritable diseases affecting bone and cartilage growth. Throughout the years, the molecular defect underlying many of the diseases has been identified. These identifications led to novel insights in the mechanisms regulating bone and cartilage growth and homeostasis. One of the pathways that is clearly important during skeletal development and bone homeostasis is the Wingless and int-1 (WNT) signaling pathway. So far, three different WNT signaling pathways have been described, which are all activated by binding of the WNT ligands to the Frizzled (FZD) receptors. In this review, we discuss the skeletal disorders that are included in the latest nosology of skeletal disorders and that are caused by genetic defects involving the WNT signaling pathway. The number of skeletal disorders caused by defects in WNT signaling genes and the clinical phenotype associated with these disorders illustrate the importance of the WNT signaling pathway during skeletal development as well as later on in life to maintain bone mass. The knowledge gained through the identification of the genes underlying these monogenic conditions is used for the identification of novel therapeutic targets. For example, the genes underlying disorders with altered bone mass are all involved in the canonical WNT signaling pathway. Consequently, targeting this pathway is one of the major strategies to increase bone mass in patients with osteoporosis. In addition to increasing the insights in the pathways regulating skeletal development and bone homeostasis, knowledge of rare skeletal dysplasias can also be used to predict possible adverse effects of these novel drug targets. Therefore, this review gives an overview of the skeletal and extra-skeletal phenotype of the different skeletal disorders linked to the WNT signaling pathway.
Identifiants
pubmed: 32328030
doi: 10.3389/fendo.2020.00165
pmc: PMC7160326
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
165Informations de copyright
Copyright © 2020 Huybrechts, Mortier, Boudin and Van Hul.
Références
BMC Med Genet. 2012 Apr 10;13:26
pubmed: 22487062
FEBS J. 2019 Dec;286(24):4832-4851
pubmed: 31677330
Eur J Med Genet. 2018 Jul;61(7):372-375
pubmed: 29427788
Am J Med Genet C Semin Med Genet. 2016 Mar;172C(1):44-51
pubmed: 26858134
PLoS Genet. 2019 Dec 12;15(12):e1008489
pubmed: 31830040
Eur J Med Genet. 2016 Nov;59(11):604-606
pubmed: 27638328
Osteoporos Int. 2016 Jul;27(7):2355-2365
pubmed: 26856585
Nat Genet. 2012 Apr 15;44(5):491-501
pubmed: 22504420
Semin Arthritis Rheum. 2013 Oct;43(2):220-40
pubmed: 23433961
Mol Syndromol. 2017 Nov;8(6):318-324
pubmed: 29230162
Science. 2012 Jul 6;337(6090):59-64
pubmed: 22653731
Am J Hum Genet. 2006 Aug;79(2):402-8
pubmed: 16826533
J Biol Chem. 2011 Jun 3;286(22):19489-500
pubmed: 21471202
Am J Hum Genet. 2018 Oct 4;103(4):535-552
pubmed: 30290150
Prog Biophys Mol Biol. 2016 Nov;122(2):93-100
pubmed: 27237581
Am J Hum Genet. 2001 Mar;68(3):577-89
pubmed: 11179006
Cell. 1982 Nov;31(1):99-109
pubmed: 6297757
Development. 1999 Dec;126(23):5515-22
pubmed: 10556075
J Bone Miner Res. 2010 Jan;25(1):82-90
pubmed: 20209645
J Clin Endocrinol Metab. 2018 Sep 1;103(9):3183-3193
pubmed: 29931216
N Engl J Med. 2016 Oct 20;375(16):1532-1543
pubmed: 27641143
J Biol. 2005;4(1):3
pubmed: 15720724
Nat Genet. 2007 Jul;39(7):833-5
pubmed: 17546031
Trends Cell Biol. 2015 May;25(5):249-64
pubmed: 25592806
Am J Hum Genet. 2013 Apr 4;92(4):565-74
pubmed: 23499309
Nature. 2013 May 23;497(7450):517-20
pubmed: 23644456
Clin Perinatol. 2015 Jun;42(2):301-19, viii
pubmed: 26042906
J Biol Chem. 2005 Jul 22;280(29):26770-5
pubmed: 15908424
J Biol Chem. 1999 Sep 17;274(38):26968-77
pubmed: 10480909
J Med Genet. 2004 Mar;41(3):213-8
pubmed: 14985386
Genes Cells. 2008 Sep;13(9):965-75
pubmed: 18691226
Am J Hum Genet. 2003 Mar;72(3):763-71
pubmed: 12579474
Am J Med Genet A. 2010 Aug;152A(8):2053-6
pubmed: 20635353
Eur J Hum Genet. 2011 Aug;19(8):875-81
pubmed: 21407258
Am J Med Genet. 1995 Jul 3;57(3):472-5
pubmed: 7677153
Genes Dev. 2004 Jul 1;18(13):1553-64
pubmed: 15198975
BMJ. 2018 Aug 29;362:k3225
pubmed: 30158200
Cancer Res. 2016 Sep 1;76(17):5103-14
pubmed: 27197191
Am J Hum Genet. 2010 May 14;86(5):696-706
pubmed: 20381006
Mol Cell. 2004 Aug 27;15(4):523-33
pubmed: 15327769
J Clin Invest. 2017 Jun 30;127(7):2678-2688
pubmed: 28628032
EMBO J. 2003 Dec 1;22(23):6267-76
pubmed: 14633986
Curr Top Dev Biol. 2006;73:43-84
pubmed: 16782455
Am J Hum Genet. 2015 Apr 2;96(4):623-30
pubmed: 25817014
Front Mol Neurosci. 2017 Mar 01;10:54
pubmed: 28298885
Hum Mol Genet. 2001 Mar 1;10(5):537-43
pubmed: 11181578
J Bone Miner Res. 2005 Jul;20(7):1254-60
pubmed: 15940380
J Hum Genet. 2017 Apr;62(5):575-576
pubmed: 28100910
J Biol Chem. 2005 May 20;280(20):19883-7
pubmed: 15778503
Am J Med Genet A. 2019 Dec;179(12):2393-2419
pubmed: 31633310
Am J Hum Genet. 2019 Jan 3;104(1):65-75
pubmed: 30595370
Cell Signal. 2018 May;45:63-70
pubmed: 29360572
Am J Hum Genet. 2018 Jan 4;102(1):27-43
pubmed: 29276006
Bone. 2017 Mar;96:51-62
pubmed: 27742500
Genomics. 1999 May 1;57(3):455-8
pubmed: 10329016
Mol Cell. 1999 Nov;4(5):839-49
pubmed: 10619030
Proc Natl Acad Sci U S A. 2005 Nov 29;102(48):17406-11
pubmed: 16293698
Am J Med Genet A. 2013 Jun;161A(6):1475-9
pubmed: 23636941
J Biochem. 2016 Apr;159(4):387-92
pubmed: 26711238
Genes Chromosomes Cancer. 2008 Jun;47(6):461-70
pubmed: 18311776
Cell. 1991 Jan 25;64(2):231
pubmed: 1846319
Hum Mol Genet. 2008 Sep 1;17(17):2644-53
pubmed: 18515319
Hum Genet. 2011 May;129(5):497-502
pubmed: 21221996
Hum Mol Genet. 2009 Nov 1;18(21):4013-21
pubmed: 19640924
Calcif Tissue Int. 2008 Jun;82(6):445-53
pubmed: 18521528
Int J Oncol. 2002 Dec;21(6):1269-73
pubmed: 12429977
Clin Case Rep. 2018 Oct 15;6(11):2252-2255
pubmed: 30455931
Am J Med Genet A. 2019 Feb;179(2):266-279
pubmed: 30569497
Aust Paediatr J. 1973 Feb;9(1):10-3
pubmed: 4708024
Hum Mutat. 2003 Jul;22(1):1-11
pubmed: 12815588
Nat Genet. 2009 Jan;41(1):95-100
pubmed: 19079258
Am J Hum Genet. 2013 Apr 4;92(4):590-7
pubmed: 23499310
Int J Dermatol. 2014 Dec;53(12):1481-4
pubmed: 25040319
Am J Med Genet A. 2010 Nov;152A(11):2832-7
pubmed: 20949531
Eur J Endocrinol. 2017 Aug;177(2):R69-R83
pubmed: 28381451
Clin Genet. 2011 Oct;80(4):383-8
pubmed: 20950377
Am J Hum Genet. 1998 Feb;62(2):391-9
pubmed: 9463328
J Med Genet. 2010 Aug;47(8):569-74
pubmed: 20610440
Am J Hum Genet. 2000 Oct;67(4):822-31
pubmed: 10986040
Cell Rep. 2015 Mar 10;10(9):1585-1598
pubmed: 25753423
Elife. 2018 Feb 06;7:
pubmed: 29405118
PLoS One. 2013 Jul 01;8(7):e68072
pubmed: 23840886
Am J Hum Genet. 2002 Jan;70(1):11-9
pubmed: 11741193
J Hand Surg Eur Vol. 2009 Apr;34(2):247-51
pubmed: 19282404
Nat Commun. 2016 May 05;7:11478
pubmed: 27145994
Nat Med. 2013 Feb;19(2):179-92
pubmed: 23389618
J Cell Biol. 1996 Nov;135(3):819-27
pubmed: 8909553
Am J Hum Genet. 2004 Mar;74(3):558-63
pubmed: 14872406
J Med Genet. 2013 May;50(5):345-8
pubmed: 23434763
Reumatol Clin. 2020 Jan - Feb;16(1):56-58
pubmed: 29463445
Am J Med Genet A. 2018 Mar;176(3):739-742
pubmed: 29383834
Sci Rep. 2016 Apr 27;6:25198
pubmed: 27117872
Endocr Pract. 2019 Mar;25(3):230-241
pubmed: 30913006
Lancet. 2017 Sep 30;390(10102):1585-1594
pubmed: 28755782
Hum Mol Genet. 2014 Apr 1;23(7):1856-68
pubmed: 24234652
Calcif Tissue Int. 2016 Apr;98(4):370-80
pubmed: 27016922
Am J Med Genet A. 2011 Feb;155A(2):332-6
pubmed: 21271649
Nat Genet. 2000 Aug;25(4):423-6
pubmed: 10932187
Am J Med Genet A. 2011 Mar;155A(3):599-604
pubmed: 21344627
Cell. 2001 Nov 16;107(4):513-23
pubmed: 11719191
PLoS One. 2010 Apr 29;5(4):e10418
pubmed: 20454682
Metabolism. 2018 Mar;80:38-47
pubmed: 29080811
BMC Genomics. 2016 Feb 25;17:136
pubmed: 26911590
Endocrine. 2016 Jun;52(3):414-26
pubmed: 26892377
J Biol Chem. 2011 Jun 3;286(22):19204-14
pubmed: 21498506
Clin Genet. 2015;87(1):34-41
pubmed: 24716670
J Cell Biochem. 2019 Nov;120(11):18588-18598
pubmed: 31271226
Am J Hum Genet. 2009 Jun;84(6):760-70
pubmed: 19481194
Genes Dev. 1997 Dec 15;11(24):3286-305
pubmed: 9407023
J Biol Chem. 2007 Oct 26;282(43):31549-57
pubmed: 17785465
Am J Med Genet A. 2007 Oct 15;143A(20):2435-43
pubmed: 17853455
Am J Hum Genet. 2019 May 2;104(5):914-924
pubmed: 30982611
Nat Genet. 2000 Aug;25(4):419-22
pubmed: 10932186
Endocrinology. 2005 Feb;146(2):655-65
pubmed: 15539560
Hum Mol Genet. 2011 Jan 15;20(2):271-85
pubmed: 20962035
Nature. 1992 Sep 17;359(6392):235-7
pubmed: 1528264
Genome Biol. 2002;3(1):REVIEWS3001
pubmed: 11806834
Science. 2007 Feb 2;315(5812):642-5
pubmed: 17204608
Curr Biol. 2010 Nov 9;20(21):1945-52
pubmed: 20970343
Nature. 2018 May;557(7706):564-569
pubmed: 29769720
Am J Hum Genet. 2015 Apr 2;96(4):612-22
pubmed: 25817016
N Engl J Med. 2013 May 9;368(19):1809-16
pubmed: 23656646
Am J Dis Child. 1969 Jun;117(6):645-51
pubmed: 5771504
N Engl J Med. 2002 May 16;346(20):1513-21
pubmed: 12015390
Int J Mol Sci. 2019 Nov 06;20(22):
pubmed: 31698687
Cell Cycle. 2006 Jan;5(1):23-6
pubmed: 16357527
J Med Genet. 2002 Feb;39(2):91-7
pubmed: 11836356
Clin Dysmorphol. 2013 Apr;22(2):47-50
pubmed: 23238279
Development. 2003 May;130(10):2129-38
pubmed: 12668627
Nat Cell Biol. 2006 May;8(5):501-8
pubmed: 16604061
Nat Genet. 1999 Aug;22(4):361-5
pubmed: 10431240
Curr Drug Saf. 2008 Sep;3(3):185-9
pubmed: 18690999
Bone. 2015 Nov;80:101-108
pubmed: 26071838
Dev Dyn. 2010 Jan;239(1):327-37
pubmed: 19918918
Endocrine. 2013 Aug;44(1):247-54
pubmed: 23325361
Nature. 2017 Nov 2;551(7678):92-94
pubmed: 29059683
J Clin Lab Anal. 2020 Feb;34(2):e23074
pubmed: 31617258
Proc Natl Acad Sci U S A. 2005 Mar 1;102(9):3324-9
pubmed: 15728361
Development. 2009 Oct;136(19):3205-14
pubmed: 19736321
Hum Mol Genet. 2014 Aug 1;23(15):4035-42
pubmed: 24634143
J Neurosci. 2009 Sep 16;29(37):11628-40
pubmed: 19759310
N Engl J Med. 2016 Jun 30;374(26):2553-2562
pubmed: 27355534
Sci Adv. 2019 Aug 14;5(8):eaaw3538
pubmed: 31453325
PLoS Genet. 2009 Dec;5(12):e1000759
pubmed: 20011118
Am J Hum Genet. 2016 Mar 3;98(3):553-561
pubmed: 26924530
J Cell Sci. 2003 Jul 1;116(Pt 13):2627-34
pubmed: 12775774
Genet Med. 2016 Nov;18(11):1158-1162
pubmed: 26963285
Am J Med Genet A. 2018 Apr;176(4):992-996
pubmed: 29575616
Dev Biol. 2011 Apr 1;352(1):1-13
pubmed: 21237142
J Biol Chem. 2009 Apr 17;284(16):10890-900
pubmed: 19208630
Exp Cell Res. 2019 Nov 1;384(1):111619
pubmed: 31525341
Cell Signal. 2018 Jul;47:52-64
pubmed: 29559363
Hum Mutat. 2018 Jun;39(6):811-815
pubmed: 29524275
Genet Test Mol Biomarkers. 2017 Dec;21(12):742-746
pubmed: 29131652
J Cell Biol. 2017 Sep 4;216(9):2911-2926
pubmed: 28696225
J Biol Chem. 2006 Dec 15;281(50):38276-84
pubmed: 17052975
Hum Mol Genet. 2015 Jun 15;24(12):3399-409
pubmed: 25759469
J Biol Chem. 2005 Jan 21;280(3):2116-25
pubmed: 15537637
J Bone Miner Res. 2016 Apr;31(4):874-81
pubmed: 26751728
Science. 2007 Mar 2;315(5816):1278-82
pubmed: 17332414
Nat Genet. 2019 Feb;51(2):258-266
pubmed: 30598549
Bone. 2019 Oct;127:228-243
pubmed: 31085352
Genet Med. 2019 Apr;21(4):1021-1026
pubmed: 30293988
N Engl J Med. 2017 Oct 12;377(15):1417-1427
pubmed: 28892457
J Bone Miner Res. 2007 May;22(5):708-16
pubmed: 17295608
J Biol Chem. 2018 Jun 22;293(25):9759-9769
pubmed: 29752411