title: Overexpression of DMP1 accelerates mineralization and alters cortical bone biomechanical properties in vivo.
abstract: Dentin matrix protein-1 (DMP1) is a key regulator of biomineralization. Here, we examine changes in structural, geometric, and material properties of cortical bone in a transgenic mouse model overexpressing DMP1. Micro-computed tomography and three-point bending were performed on 90 femora of wild type and transgenic mice at 1, 2, 4, and 6 months. Fourier transform infrared imaging was performed at 2 months. We found that the transgenic femurs were longer (p<0.01), more robust in cross-section (p<0.05), stronger (p<0.05), but had less post-yield strain and displacement (p<0.01), and higher tissue mineral density (p<0.01) than the wild type femurs at 1 and 2 months. At 2 months, the transgenic femurs also had a higher mineral-to-matrix ratio (p<0.05) and lower carbonate substitution (p<0.05) compared to wild type femurs. These findings indicate that increased mineralization caused by overexpressing DMP1 led to increased structural cortical bone properties associated with decreased ductility during the early post-natal period.
authors.affiliation: Department of Anatomy and Cell Biology, Rush Medical College, 600 S Paulina St., Rm 507, Chicago, IL 60612, USA. ankush_bhatia@rush.edu
authors.forename: Ankush
authors.initials: A
authors.lastname: Bhatia
authors.forename: Michael
authors.initials: M
authors.lastname: Albazzaz
authors.forename: Alejandro A
authors.initials: AA
authors.lastname: Espinoza Orías
authors.forename: Nozomu
authors.initials: N
authors.lastname: Inoue
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Miller
authors.forename: Alvin
authors.initials: A
authors.lastname: Acerbo
authors.forename: Anne
authors.initials: A
authors.lastname: George
authors.forename: Dale R
authors.initials: DR
authors.lastname: Sumner
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002113:Calcification, Physiologic / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005269:Femur / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000502:physiology; D015870:Gene Expression; D008422:Materials Testing; D055595:Mechanical Phenomena; D051379:Mice; D008822:Mice, Transgenic; D055114:X-Ray Microtomography
chemical_list: D016326:Extracellular Matrix Proteins
references.citation: Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4516-21
references.pmid: 11287660
references.citation: J Biomech. 2005 Mar;38(3):467-75
references.pmid: 15652544
references.citation: J Biomech. 2003 Oct;36(10):1497-502
references.pmid: 14499298
references.citation: Connect Tissue Res. 2003;44 Suppl 1:33-40
references.pmid: 12952171
references.citation: J Bone Miner Metab. 2004;22(5):430-8
references.pmid: 15316863
references.citation: J Bone Miner Res. 2001 Oct;16(10):1821-8
references.pmid: 11585346
references.citation: J Biol Chem. 2003 May 9;278(19):17500-8
references.pmid: 12615915
references.citation: J Bone Miner Res. 1998 Mar;13(3):422-31
references.pmid: 9525343
references.citation: Nat Mater. 2003 Aug;2(8):552-8
references.pmid: 12872163
references.citation: J Bone Miner Res. 1999 Dec;14(12):2159-66
references.pmid: 10620076
references.citation: J Bone Miner Res. 1997 Dec;12(12):2040-9
references.pmid: 9421236
references.citation: J Histochem Cytochem. 2007 Apr;55(4):403-9
references.pmid: 17210923
references.citation: Nat Genet. 2006 Nov;38(11):1310-5
references.pmid: 17033621
references.citation: J Biol Chem. 1993 Jun 15;268(17):12624-30
references.pmid: 8509401
references.citation: Biochem Biophys Res Commun. 2001 Jan 19;280(2):460-5
references.pmid: 11162539
references.citation: Kidney Int. 2005 Jul;68(1):155-66
references.pmid: 15954904
references.citation: Bone. 2007 Dec;41(6):1017-24
references.pmid: 17931992
references.citation: J Bone Miner Res. 2005 Dec;20(12):2169-77
references.pmid: 16294270
references.citation: J Biol Chem. 2005 Feb 18;280(7):6197-203
references.pmid: 15590631
references.citation: J Dent Res. 1997 Mar;76(3):754-60
references.pmid: 9109824
references.citation: J Biol Chem. 2010 Nov 19;285(47):36339-51
references.pmid: 20841352
references.citation: Calcif Tissue Int. 2004 May;74(5):469-75
references.pmid: 14961209
references.citation: Bone. 2009 Jul;45(1):84-90
references.pmid: 19332167
references.citation: Bone. 2008 Oct;43(4):717-23
references.pmid: 18639658
references.citation: J Bone Miner Res. 2010 Jul;25(7):1468-86
references.pmid: 20533309
references.citation: J Bone Miner Res. 2007 Jul;22(7):1037-45
references.pmid: 17402847
references.citation: Calcif Tissue Int. 1996 Dec;59(6):480-7
references.pmid: 8939775
references.citation: J Dent Res. 2004 Sep;83(9):664-70
references.pmid: 15329369