title: Enhanced BMP signaling prevents degeneration and leads to endochondral ossification of Meckel's cartilage in mice.
abstract: Meckel's cartilage is a transient supporting tissue of the embryonic mandible in mammals, and disappears by taking different ultimate cell fate along the distal-proximal axis, with the majority (middle portion) undergoing degeneration and chondroclastic resorption. While a number of factors have been implicated in the degeneration and resorption processes, signaling pathways that trigger this degradation are currently unknown. BMP signaling has been implicated in almost every step of chondrogenesis. In this study, we used Noggin mutant mice as a model for gain-of-BMP signaling function to investigate the function of BMP signaling in Meckel's cartilage development, with a focus on the middle portion. We showed that Bmp2 and Bmp7 are expressed in early developing Meckels' cartilage, but their expression disappears thereafter. In contrast, Noggin is expressed constantly in Meckel's cartilage throughout the entire gestation period. In the absence of Noggin, Meckel's cartilage is significantly thickened attributing to dramatically elevated cell proliferation rate associated with enhanced phosphorylated Smad1/5/8 expression. Interestingly, instead of taking a degeneration fate, the middle portion of Meckel's cartilage in Noggin mutants undergoes chondrogenic differentiation and endochondral ossification contributing to the forming mandible. Chondrocyte-specific expression of a constitutively active form of BMPRIa but not BMPRIb leads to enlargement of Meckel's cartilage, phenocopying the consequence of Noggin deficiency. Our results demonstrate that elevated BMP signaling prevents degeneration and leads to endochondral ossification of Meckel's cartilage, and support the idea that withdrawal of BMP signaling is required for normal Meckel's cartilage development and ultimate cell fate.
authors.affiliation: Department of Operative Dentistry and Endodontics, College of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi Province, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yuqian
authors.initials: Y
authors.lastname: Zheng
authors.forename: Di
authors.initials: D
authors.lastname: Chen
authors.forename: YiPing
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism*; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002356:Cartilage / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D019902:Chondrocytes / Q000378:metabolism; D020219:Chondrogenesis; D004622:Embryo, Mammalian / Q000378:metabolism / Q000473:pathology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008334:Mandible / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism; D051379:Mice; D009999:Ossification, Heterotopic / Q000378:metabolism*; D010012:Osteogenesis; D010766:Phosphorylation; D011247:Pregnancy; D015398:Signal Transduction; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism; D000099176:Noggin Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D055419:Bone Morphogenetic Protein 7; D052005:Bone Morphogenetic Protein Receptors, Type I; D002352:Carrier Proteins; D051898:Smad1 Protein; D000099176:Noggin Protein; C525719:Bmp2 protein, mouse; C497401:Smad1 protein, mouse; C525820:bmp7 protein, mouse; C498212:Bmpr1a protein, mouse
keywords: BMP signaling; BmprIa; Development; Differentiation; Meckel′s cartilage; Noggin
references.citation: Cell Tissue Res. 2001 Apr;304(1):67-80
references.pmid: 11383888
references.citation: J Biol Chem. 2002 Sep 13;277(37):33545-58
references.pmid: 12082094
references.citation: Cell Tissue Res. 2007 Apr;328(1):137-51
references.pmid: 17136358
references.citation: Hum Mol Genet. 2011 Oct 15;20(20):4005-15
references.pmid: 21821669
references.citation: Acta Histochem. 2011 Feb;113(2):194-200
references.pmid: 19853894
references.citation: J Bone Miner Res. 1999 Oct;14(10):1734-41
references.pmid: 10491221
references.citation: Dev Biol. 1995 Aug;170(2):387-96
references.pmid: 7649371
references.citation: Development. 2009 Apr;136(7):1093-104
references.pmid: 19224984
references.citation: Genes Dev. 1997 Sep 1;11(17):2191-203
references.pmid: 9303535
references.citation: J Dent Res. 2012 Apr;91(4):394-400
references.pmid: 22302143
references.citation: Int J Dev Biol. 2002 Mar;46(2):243-53
references.pmid: 11934153
references.citation: Nat Genet. 1999 Jan;21(1):70-1
references.pmid: 9916792
references.citation: Dev Biol. 2000 Jan 15;217(2):323-32
references.pmid: 10625557
references.citation: Differentiation. 1999 Jan;64(2):67-76
references.pmid: 10234804
references.citation: Science. 1998 May 29;280(5368):1455-7
references.pmid: 9603738
references.citation: Cell Tissue Res. 2010 Dec;342(3):401-10
references.pmid: 21079999
references.citation: Int J Dev Biol. 1999 Nov;43(8):795-807
references.pmid: 10707903
references.citation: Development. 2001 Nov;128(22):4523-34
references.pmid: 11714677
references.citation: J Dent Res. 1969 Nov-Dec;48(6):1258-63
references.pmid: 5262056
references.citation: J Dent Res. 1953 Jun;32(3):398-410
references.pmid: 13061679
references.citation: Cell. 1996 Aug 23;86(4):599-606
references.pmid: 8752214
references.citation: Anat Embryol (Berl). 1997 Aug;196(2):107-13
references.pmid: 9278155
references.citation: Nat Genet. 1999 May;22(1):85-9
references.pmid: 10319868
references.citation: Anat Embryol (Berl). 1998 Jun;197(6):439-50
references.pmid: 9682975
references.citation: Growth Factors. 2004 Dec;22(4):233-41
references.pmid: 15621726
references.citation: Development. 2000 Feb;127(3):621-30
references.pmid: 10631182
references.citation: Nat Rev Mol Cell Biol. 2012 Oct;13(10):616-30
references.pmid: 22992590
references.citation: Dev Biol. 2001 Dec 15;240(2):457-73
references.pmid: 11784076
references.citation: Genesis. 2007 Jan;45(1):44-50
references.pmid: 17211877
references.citation: Dev Biol. 2009 Jun 1;330(1):131-41
references.pmid: 19341725
references.citation: J Anat. 2005 Oct;207(4):325-37
references.pmid: 16191162
references.citation: Nature. 2002 Dec 12;420(6916):636-42
references.pmid: 12478285
references.citation: Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18023-7
references.pmid: 16322106
references.citation: Dev Dyn. 2004 Sep;231(1):136-47
references.pmid: 15305294
references.citation: Eur J Oral Sci. 2007 Jun;115(3):212-23
references.pmid: 17587297
references.citation: Anat Rec (Hoboken). 2012 May;295(5):734-41
references.pmid: 22371349
references.citation: Development. 2003 Nov;130(21):5269-80
references.pmid: 12975342
references.citation: Dev Biol. 1986 Sep;117(1):90-101
references.pmid: 3527817
references.citation: J Dent Res. 1971 Sep-Oct;50(5):1260-7
references.pmid: 5285785
references.citation: Dev Biol. 1988 Sep;129(1):48-60
references.pmid: 3044881
references.citation: Genes Dev. 1998 May 15;12(10):1438-52
references.pmid: 9585504
references.citation: Dev Biol. 2011 Feb 15;350(2):337-47
references.pmid: 21147086
references.citation: Dev Biol. 2000 Apr 15;220(2):154-67
references.pmid: 10753507
references.citation: Development. 2000 Feb;127(3):605-19
references.pmid: 10631181
references.citation: Dev Dyn. 2002 May;224(1):69-78
references.pmid: 11984875
references.citation: Dev Dyn. 2011 Nov;240(11):2466-73
references.pmid: 21953591
references.citation: Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9360-5
references.pmid: 12878728
references.citation: Anat Rec. 1973 Jul;176(3):345-59
references.pmid: 4716419
references.citation: Tissue Cell. 2000 Jun;32(3):207-15
references.pmid: 11037790
references.citation: Proc Natl Acad Sci U S A. 2005 Apr 5;102(14):5062-7
references.pmid: 15781876
references.citation: Dev Biol. 2010 Nov 1;347(1):109-21
references.pmid: 20727875
references.citation: Dev Biol. 2011 Jan 15;349(2):451-61
references.pmid: 21034733
references.citation: Dev Biol. 1994 Mar;162(1):85-103
references.pmid: 8125201
references.citation: PLoS One. 2011;6(9):e24608
references.pmid: 21935430