title: Smad3 binds Scleraxis and Mohawk and regulates tendon matrix organization.
abstract: TGFβ plays a critical role in tendon formation and healing. While its downstream effector Smad3 has been implicated in the healing process, little is known about the role of Smad3 in normal tendon development or tenocyte gene expression. Using mice deficient in Smad3 (Smad3(-/-) ), we show that Smad3 ablation disrupts tendon architecture and has a dramatic impact on normal gene and protein expression during development as well as in mature tendon. In developing and adult tendon, loss of Smad3 results in reduced protein expression of the matrix components Collagen 1 and Tenascin-C. Additionally, when compared to wild type, tendon from adult Smad3(-/-) mice shows a down regulation of key tendon marker genes. Finally, we have established that Smad3 has the ability to physically interact with the critical transcriptional regulators Scleraxis and Mohawk. Together these results indicate a central role for Smad3 in normal tendon formation and in the maintenance of mature tendon.
authors: Department of Orthopaedic Surgery, University of California, San Francisco, 1500 Owens St., San Francisco, CA 94158, USA.
authors: Ellora
authors: E
authors: Berthet
authors: Carol
authors: C
authors: Chen
authors: Kristin
authors: K
authors: Butcher
authors: Richard A
authors: RA
authors: Schneider
authors: Tamara
authors: T
authors: Alliston
authors: Mohana
authors: M
authors: Amirtharajah
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism; D004622:Embryo, Mammalian; D005109:Extracellular Matrix / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism*; D019063:Tenascin / Q000378:metabolism; D013710:Tendons / Q000166:cytology / Q000196:embryology / Q000378:metabolism*
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D024042:Collagen Type I; D018398:Homeodomain Proteins; D051900:Smad3 Protein; D019063:Tenascin; C503815:Scx protein, mouse; C497791:Smad3 protein, mouse; C510657:mohawk protein, mouse
keywords: Mohawk; Scleraxis; Smad3; TGFβ; Tendon
references: Plast Reconstr Surg. 1997 Sep;100(4):937-44
references: 9290662
references: Dev Dyn. 2009 Mar;238(3):572-80
references: 19235719
references: J Biol Chem. 2003 Mar 14;278(11):9609-19
references: 12524424
references: J Biol Chem. 2009 Oct 23;284(43):29988-96
references: 19717568
references: J Am Soc Nephrol. 2011 Aug;22(8):1462-74
references: 21784902
references: J Biol Chem. 2005 Mar 4;280(9):8343-50
references: 15623506
references: J Immunol. 2005 Jul 1;175(1):547-54
references: 15972691
references: Methods. 2001 Dec;25(4):402-8
references: 11846609
references: Development. 2007 Jul;134(14):2697-708
references: 17567668
references: Development. 2009 Apr;136(8):1351-61
references: 19304887
references: Genes Dev. 2001 Nov 15;15(22):2950-66
references: 11711431
references: J Orthop Res. 2006 Mar;24(3):569-75
references: 16463363
references: Proc Natl Acad Sci U S A. 2005 Dec 27;102(52):18813-8
references: 16354837
references: J Bone Miner Res. 2001 Oct;16(10):1754-64
references: 11585338
references: Cell Tissue Res. 2009 Apr;336(1):79-89
references: 19221802
references: J Bone Miner Res. 1994 Jun;9(6):855-63
references: 8079661
references: Wound Repair Regen. 2008 May-Jun;16(3):399-407
references: 18471258
references: J Orthop Res. 2011 May;29(5):684-93
references: 20842701
references: Mol Cell Biol. 2010 Oct;30(20):4797-807
references: 20696843
references: EMBO J. 2001 May 1;20(9):2254-72
references: 11331591
references: Biochim Biophys Acta. 1991 Jun 13;1089(2):241-3
references: 2054384
references: J Cell Physiol. 1997 Feb;170(2):145-52
references: 9009143
references: J Biol Chem. 2005 Oct 21;280(42):35203-8
references: 16109717
references: Proc Natl Acad Sci U S A. 2008 Jan 8;105(1):388-93
references: 18162552
references: EMBO J. 2005 Jul 20;24(14):2543-55
references: 15990875