title: Decreased Mechanical Strength and Collagen Content in SPARC-Null Periodontal Ligament Is Reversed by Inhibition of Transglutaminase Activity.
abstract: The periodontal ligament (PDL) is a critical tissue that provides a physical link between the mineralized outer layer of the tooth and the alveolar bone. The PDL is composed primarily of nonmineralized fibrillar collagens. Expression of secreted protein acidic and rich in cysteine (SPARC/osteonectin), a collagen-binding matricellular protein, has been shown to be essential for collagen homeostasis in PDL. In the absence of SPARC, PDL collagen fibers are smaller and less dense than fibers that constitute WT PDL. The aim of this study was to identify cellular mechanisms by which SPARC affected collagen fiber assembly and morphology in PDL. Cross-linking of fibrillar collagens is one parameter that is known to affect insoluble collagen incorporation and fiber morphology. Herein, the reduction in collagen fiber size and quantity in the absence of SPARC expression was shown to result in a PDL with reduced molar extraction force in comparison to that of WT mice (C57Bl/6J). Furthermore, an increase in transglutaminase activity was found in SPARC-null PDL by biochemical analyses that was supported by immunohistochemical results. Specifically, collagen I was identified as a substrate for transglutaminase in PDL and transglutaminase activity on collagen I was found to be greater in SPARC-null tissues in comparison to WT. Strikingly, inhibition of transglutaminase activity in SPARC-null PDL resulted in increases in both collagen fiber thickness and in collagen content, whereas transglutaminase inhibitors injected into WT mice resulted in increases in collagen fiber thickness only. Furthermore, PDL treated with transglutaminase inhibitors exhibited increases in molar extraction force in WT and in SPARC-null mice. Thus, SPARC is proposed to act as a critical regulator of transglutaminase activity on collagen I with implications for mechanical strength of tissues.
authors.affiliation: Department of Craniofacial Biology, Medical University of South Carolina, Charleston, Clemson, SC, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Trombetta-eSilva
authors.affiliation: Department of Craniofacial Biology, Medical University of South Carolina, Charleston, Clemson, SC, USA.
authors.forename: Emilie A
authors.initials: EA
authors.lastname: Rosset
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, USA.
authors.forename: R Glenn
authors.initials: RG
authors.lastname: Hepfer
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, USA.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Wright
authors.affiliation: Gazes Cardiac Research Institute, Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA.
authors.forename: Catalin
authors.initials: C
authors.lastname: Baicu
authors.affiliation: Department of Craniofacial Biology, Medical University of South Carolina, Charleston, Clemson, SC, USA.|Department of Bioengineering, Clemson University, Clemson, SC, USA.
authors.forename: Hai
authors.initials: H
authors.lastname: Yao
authors.affiliation: Department of Craniofacial Biology, Medical University of South Carolina, Charleston, Clemson, SC, USA.|Gazes Cardiac Research Institute, Division of Cardiology, Department of Medicine, Medical University of South Carolina, Charleston, SC, USA.|Ralph H. Johnson Department of Veterans Affairs Medical Center, Charleston, SC, USA.
authors.forename: Amy D
authors.initials: AD
authors.lastname: Bradshaw
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D015676:Osteonectin / Q000172:deficiency*; D010513:Periodontal Ligament / Q000378:metabolism* / Q000473:pathology; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D015676:Osteonectin; C578250:SPARC protein, mouse; D011503:Transglutaminases
keywords: BONE MATRIX; CROSS-LINKS; DENTAL BIOLOGY; EXTRACELLULAR MATRIX; NONCOLLAGENOUS PROTEINS
references.citation: J Biol Chem. 2014 Jul 4;289(27):18873-9
references.pmid: 24849606
references.citation: PLoS One. 2014;9(11):e110948
references.pmid: 25364829
references.citation: J Clin Invest. 2000 Apr;105(7):915-23
references.pmid: 10749571
references.citation: J Cell Sci. 2001 Aug;114(Pt 16):2989-3000
references.pmid: 11686302
references.citation: Nature. 2002 Jan 10;415(6868):175-9
references.pmid: 11805836
references.citation: Endocrinology. 2003 Jun;144(6):2588-96
references.pmid: 12746322
references.citation: J Invest Dermatol. 2003 Jun;120(6):949-55
references.pmid: 12787119
references.citation: Am J Pathol. 2003 Sep;163(3):1045-56
references.pmid: 12937145
references.citation: Mol Cell Biochem. 1984;58(1-2):63-8
references.pmid: 6143254
references.citation: Annu Rev Biochem. 1984;53:717-48
references.pmid: 6148038
references.citation: J Biol Chem. 1987 Jan 25;262(3):1022-4
references.pmid: 2879837
references.citation: FASEB J. 1991 Oct;5(13):2814-23
references.pmid: 1916105
references.citation: J Cell Biol. 1995 May;129(3):881-92
references.pmid: 7730416
references.citation: Exp Cell Res. 1998 Feb 25;239(1):119-38
references.pmid: 9511731
references.citation: Periodontol 2000. 1997 Feb;13:20-40
references.pmid: 9567922
references.citation: Invest Ophthalmol Vis Sci. 1998 Dec;39(13):2674-80
references.pmid: 9856777
references.citation: J Biol Chem. 1999 Jan 15;274(3):1729-35
references.pmid: 9880554
references.citation: Front Biosci. 2006;11:1591-606
references.pmid: 16368540
references.citation: FASEB J. 2006 Oct;20(12):2133-5
references.pmid: 16940435
references.citation: Biomaterials. 2008 Jul;29(20):3034-45
references.pmid: 18420267
references.citation: J Biomed Mater Res A. 2009 Jun 15;89(4):1001-10
references.pmid: 18478551
references.citation: Physiol Rev. 2009 Jul;89(3):991-1023
references.pmid: 19584319
references.citation: Biomaterials. 2010 Jun;31(16):4600-8
references.pmid: 20223517
references.citation: J Histochem Cytochem. 2010 Oct;58(10):871-9
references.pmid: 20566756
references.citation: Connect Tissue Res. 2011 Feb;52(1):2-17
references.pmid: 21182410
references.citation: PLoS One. 2011;6(1):e15893
references.pmid: 21283799
references.citation: J Dent Res. 2011 Apr;90(4):477-82
references.pmid: 21191126
references.citation: Am J Respir Cell Mol Biol. 2011 Apr;44(4):548-55
references.pmid: 20558776
references.citation: J Periodontol. 2011 Sep;82(9):1223-37
references.pmid: 21284553
references.citation: J Cell Physiol. 2012 Jul;227(7):2936-46
references.pmid: 21959563
references.citation: Am J Physiol Heart Circ Physiol. 2012 Apr 1;302(7):H1355-66
references.pmid: 22307675
references.citation: PLoS One. 2012;7(8):e44159
references.pmid: 22952912
references.citation: FEBS Lett. 2012 Sep 21;586(19):3421-8
references.pmid: 22858378
references.citation: Matrix Biol. 2013 Mar 11;32(2):106-16
references.pmid: 23357642
references.citation: FEBS J. 2013 May;280(10):2120-37
references.pmid: 23331954
references.citation: Bone. 2014 Feb;59:127-38
references.pmid: 24246248
references.citation: J Biol Chem. 2014 Jan 10;289(2):921-9
references.pmid: 24265319
references.citation: Amino Acids. 2014 Jul;46(7):1751-61
references.pmid: 24710705