Quantification of Skeletal Phenotype of Transgenic Mice Overexpressing DMP1 Using ΜCT and Mechanical Testing

Dentin matrix protein 1 (DMP1) is a key regulator of biomineralization. Here, we examine both trabecular architecture and density at the distal femoral metaphysis and structural, geometrical, and material properties of femoral midshaft 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. At the distal end of the mouse femur, we found increased bone volume at 1 month (p<0.001), but decreased bone volume at 2 (pO.OOl), 4 (p<0.05), and 6 months (p<0.001) and increased material density at 2 months (p<0.001) in the transgenic mice. We found that the transgenic femurs were longer (p<0.01), more robust in cross-section (p<0.05), and stronger (p<0.05), but had less post-yield strain and displacement (p<0.01), and higher material density (p<0.01) than the wild type femurs at 1 and 2 months. These findings indicate that overexpression of DMP 1 accelerates mineralization of trabecular and cortical bone, alters biomechanical properties of cortical bone, and depresses trabecular bone volume.

Year	Entry
2003	Gluhak-Heinrich J, Ye L, Bonewald LF, Feng JQ, MacDougall M, Harris SE, Pavlin D. Mechanical loading stimulates dentin matrix protein 1 (DMP1) expression in osteocytes in vivo. J Bone Miner Res. May 2003;18(5):807-817.
2005	Schriefer JL, Robling AG, Warden SJ, Fournier AJ, Mason JJ, Turner CH. A comparison of mechanical properties derived from multiple skeletal sites in mice. J Biomech. March 2005;38(3):467-475.
2001	Young MF, Xu T. Creating transgeneic mice to study skeletal function. In: Cowin SC, ed. Bone Mechanics Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2001:chap 4.
2001	van der Meulen MCH, Jepsen KJ, Mikić B. Understanding bone strength: size isn’t everything. Bone. July 2001;29(1):101-104.
1962	Currey JD. Strength of bone. Nature. August 4, 1962;195:513-514.
1989	Feldkamp LA, Goldstein SA, Parfitt MA, Jesion G, Kleerekoper M. The direct examination of three‐dimensional bone architecture in vitro by computed tomography. J Bone Miner Res. 1989;4(1):3-11.
2006	Feng JQ, Ward LM, Liu S, Lu Y, Xie Y, Yuan B, Yu X, Rauch F, Davis SI, Zhang S, Rios H, Drezner MK, Quarles LD, Bonewald LF, White KE. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet. November 2006;38(11):1310-1315.

Year

Entry

2003

Gluhak-Heinrich J, Ye L, Bonewald LF, Feng JQ, MacDougall M, Harris SE, Pavlin D. Mechanical loading stimulates dentin matrix protein 1 (DMP1) expression in osteocytes in vivo. J Bone Miner Res. May 2003;18(5):807-817.

2005

Schriefer JL, Robling AG, Warden SJ, Fournier AJ, Mason JJ, Turner CH. A comparison of mechanical properties derived from multiple skeletal sites in mice. J Biomech. March 2005;38(3):467-475.

2001

Young MF, Xu T. Creating transgeneic mice to study skeletal function. In: Cowin SC, ed. Bone Mechanics Handbook. 2nd ed. Boca Raton, FL: CRC Press; 2001:chap 4.

2001

van der Meulen MCH, Jepsen KJ, Mikić B. Understanding bone strength: size isn’t everything. Bone. July 2001;29(1):101-104.

1962

Currey JD. Strength of bone. Nature. August 4, 1962;195:513-514.

1989

Feldkamp LA, Goldstein SA, Parfitt MA, Jesion G, Kleerekoper M. The direct examination of three‐dimensional bone architecture in vitro by computed tomography. J Bone Miner Res. 1989;4(1):3-11.

2006

Feng JQ, Ward LM, Liu S, Lu Y, Xie Y, Yuan B, Yu X, Rauch F, Davis SI, Zhang S, Rios H, Drezner MK, Quarles LD, Bonewald LF, White KE. Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism. Nat Genet. November 2006;38(11):1310-1315.