Bone biomechanical properties in LRP5 mutant mice

M. P. Akhter, D. J. Wells, S. J. Short, D. M. Cullen, M. L. Johnson, G. R. Haynatzki, P. Babij, K. M. Allen, P. J. Yaworsky, F. Bex, R. R. Recker

Research output: Contribution to journalArticle

113 Citations (Scopus)

Abstract

The mutation responsible for the high bone mass (HBM) phenotype has been postulated to act through the adaptive response of bone to mechanical load resulting in denser and stronger skeletons in humans and animals. The bone phenotype of members of a HBM family is characterized by normally shaped bones that are exceptionally dense, particularly at load bearing sites [Cancer Res. 59 (1999) 1572]. The high bone mass (HBM) mutation was identified as a glycine to valine substitution at amino acid residue 171 in the gene coding for low-density lipoprotein receptor-related protein 5 (LRP5) [Bone Miner. Res. 16(4) (2001) 758]. Thus, efforts have focused on the examination of the role of LRP5 and the G171V mutation in bone mechanotransduction responses [J. Bone Miner. Res 18 (2002) 960]. Transgenic mice expressing the human G171V mutation have been shown to have skeletal phenotypes remarkably similar to those seen in affected individuals. In this study, we have identified differences in biomechanical (structural and apparent material) properties, bone mass/ash, and bone stiffness of cortical and cancellous bone driven by the G171V mutation in LRP5. As in humans, the LRP5 G171V plays an important role in regulating bone structural phenotypes in mice. These bone phenotypes include greater structural and apparent material properties in HBM HET as compared to non-transgenic littermates (NTG) mice. Body size and weight in HBM HET were similar to that in NTG control mice. However, the LRP5 G171V mutation in HET mice results in a skeleton that has greater structural (femoral shaft, femoral neck, tibiae, vertebral body) and apparent material (vertebral body) strength, percent bone ash weight (ulnae), and tibial stiffness. Despite similar body weight to NTG mice, the denser and stiffer bones in G171V mice may represent greater bone formation sensitivity to normal mechanical stimuli resulting in an overadaptation of skeleton to weight-related forces.

Original languageEnglish (US)
Pages (from-to)162-169
Number of pages8
JournalBone
Volume35
Issue number1
DOIs
StatePublished - Jul 1 2004

Fingerprint

Low Density Lipoprotein Receptor-Related Protein-5
Bone and Bones
Mutation
Skeleton
Phenotype
Body Weight
Weights and Measures

Keywords

  • Bone ash
  • High bone mass
  • LRP5 G171V mutation

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Histology

Cite this

Akhter, M. P., Wells, D. J., Short, S. J., Cullen, D. M., Johnson, M. L., Haynatzki, G. R., ... Recker, R. R. (2004). Bone biomechanical properties in LRP5 mutant mice. Bone, 35(1), 162-169. https://doi.org/10.1016/j.bone.2004.02.018

Bone biomechanical properties in LRP5 mutant mice. / Akhter, M. P.; Wells, D. J.; Short, S. J.; Cullen, D. M.; Johnson, M. L.; Haynatzki, G. R.; Babij, P.; Allen, K. M.; Yaworsky, P. J.; Bex, F.; Recker, R. R.

In: Bone, Vol. 35, No. 1, 01.07.2004, p. 162-169.

Research output: Contribution to journalArticle

Akhter, MP, Wells, DJ, Short, SJ, Cullen, DM, Johnson, ML, Haynatzki, GR, Babij, P, Allen, KM, Yaworsky, PJ, Bex, F & Recker, RR 2004, 'Bone biomechanical properties in LRP5 mutant mice', Bone, vol. 35, no. 1, pp. 162-169. https://doi.org/10.1016/j.bone.2004.02.018
Akhter MP, Wells DJ, Short SJ, Cullen DM, Johnson ML, Haynatzki GR et al. Bone biomechanical properties in LRP5 mutant mice. Bone. 2004 Jul 1;35(1):162-169. https://doi.org/10.1016/j.bone.2004.02.018
Akhter, M. P. ; Wells, D. J. ; Short, S. J. ; Cullen, D. M. ; Johnson, M. L. ; Haynatzki, G. R. ; Babij, P. ; Allen, K. M. ; Yaworsky, P. J. ; Bex, F. ; Recker, R. R. / Bone biomechanical properties in LRP5 mutant mice. In: Bone. 2004 ; Vol. 35, No. 1. pp. 162-169.
@article{a54af790ea714fde8058797d9c2ff478,
title = "Bone biomechanical properties in LRP5 mutant mice",
abstract = "The mutation responsible for the high bone mass (HBM) phenotype has been postulated to act through the adaptive response of bone to mechanical load resulting in denser and stronger skeletons in humans and animals. The bone phenotype of members of a HBM family is characterized by normally shaped bones that are exceptionally dense, particularly at load bearing sites [Cancer Res. 59 (1999) 1572]. The high bone mass (HBM) mutation was identified as a glycine to valine substitution at amino acid residue 171 in the gene coding for low-density lipoprotein receptor-related protein 5 (LRP5) [Bone Miner. Res. 16(4) (2001) 758]. Thus, efforts have focused on the examination of the role of LRP5 and the G171V mutation in bone mechanotransduction responses [J. Bone Miner. Res 18 (2002) 960]. Transgenic mice expressing the human G171V mutation have been shown to have skeletal phenotypes remarkably similar to those seen in affected individuals. In this study, we have identified differences in biomechanical (structural and apparent material) properties, bone mass/ash, and bone stiffness of cortical and cancellous bone driven by the G171V mutation in LRP5. As in humans, the LRP5 G171V plays an important role in regulating bone structural phenotypes in mice. These bone phenotypes include greater structural and apparent material properties in HBM HET as compared to non-transgenic littermates (NTG) mice. Body size and weight in HBM HET were similar to that in NTG control mice. However, the LRP5 G171V mutation in HET mice results in a skeleton that has greater structural (femoral shaft, femoral neck, tibiae, vertebral body) and apparent material (vertebral body) strength, percent bone ash weight (ulnae), and tibial stiffness. Despite similar body weight to NTG mice, the denser and stiffer bones in G171V mice may represent greater bone formation sensitivity to normal mechanical stimuli resulting in an overadaptation of skeleton to weight-related forces.",
keywords = "Bone ash, High bone mass, LRP5 G171V mutation",
author = "Akhter, {M. P.} and Wells, {D. J.} and Short, {S. J.} and Cullen, {D. M.} and Johnson, {M. L.} and Haynatzki, {G. R.} and P. Babij and Allen, {K. M.} and Yaworsky, {P. J.} and F. Bex and Recker, {R. R.}",
year = "2004",
month = "7",
day = "1",
doi = "10.1016/j.bone.2004.02.018",
language = "English (US)",
volume = "35",
pages = "162--169",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Bone biomechanical properties in LRP5 mutant mice

AU - Akhter, M. P.

AU - Wells, D. J.

AU - Short, S. J.

AU - Cullen, D. M.

AU - Johnson, M. L.

AU - Haynatzki, G. R.

AU - Babij, P.

AU - Allen, K. M.

AU - Yaworsky, P. J.

AU - Bex, F.

AU - Recker, R. R.

PY - 2004/7/1

Y1 - 2004/7/1

N2 - The mutation responsible for the high bone mass (HBM) phenotype has been postulated to act through the adaptive response of bone to mechanical load resulting in denser and stronger skeletons in humans and animals. The bone phenotype of members of a HBM family is characterized by normally shaped bones that are exceptionally dense, particularly at load bearing sites [Cancer Res. 59 (1999) 1572]. The high bone mass (HBM) mutation was identified as a glycine to valine substitution at amino acid residue 171 in the gene coding for low-density lipoprotein receptor-related protein 5 (LRP5) [Bone Miner. Res. 16(4) (2001) 758]. Thus, efforts have focused on the examination of the role of LRP5 and the G171V mutation in bone mechanotransduction responses [J. Bone Miner. Res 18 (2002) 960]. Transgenic mice expressing the human G171V mutation have been shown to have skeletal phenotypes remarkably similar to those seen in affected individuals. In this study, we have identified differences in biomechanical (structural and apparent material) properties, bone mass/ash, and bone stiffness of cortical and cancellous bone driven by the G171V mutation in LRP5. As in humans, the LRP5 G171V plays an important role in regulating bone structural phenotypes in mice. These bone phenotypes include greater structural and apparent material properties in HBM HET as compared to non-transgenic littermates (NTG) mice. Body size and weight in HBM HET were similar to that in NTG control mice. However, the LRP5 G171V mutation in HET mice results in a skeleton that has greater structural (femoral shaft, femoral neck, tibiae, vertebral body) and apparent material (vertebral body) strength, percent bone ash weight (ulnae), and tibial stiffness. Despite similar body weight to NTG mice, the denser and stiffer bones in G171V mice may represent greater bone formation sensitivity to normal mechanical stimuli resulting in an overadaptation of skeleton to weight-related forces.

AB - The mutation responsible for the high bone mass (HBM) phenotype has been postulated to act through the adaptive response of bone to mechanical load resulting in denser and stronger skeletons in humans and animals. The bone phenotype of members of a HBM family is characterized by normally shaped bones that are exceptionally dense, particularly at load bearing sites [Cancer Res. 59 (1999) 1572]. The high bone mass (HBM) mutation was identified as a glycine to valine substitution at amino acid residue 171 in the gene coding for low-density lipoprotein receptor-related protein 5 (LRP5) [Bone Miner. Res. 16(4) (2001) 758]. Thus, efforts have focused on the examination of the role of LRP5 and the G171V mutation in bone mechanotransduction responses [J. Bone Miner. Res 18 (2002) 960]. Transgenic mice expressing the human G171V mutation have been shown to have skeletal phenotypes remarkably similar to those seen in affected individuals. In this study, we have identified differences in biomechanical (structural and apparent material) properties, bone mass/ash, and bone stiffness of cortical and cancellous bone driven by the G171V mutation in LRP5. As in humans, the LRP5 G171V plays an important role in regulating bone structural phenotypes in mice. These bone phenotypes include greater structural and apparent material properties in HBM HET as compared to non-transgenic littermates (NTG) mice. Body size and weight in HBM HET were similar to that in NTG control mice. However, the LRP5 G171V mutation in HET mice results in a skeleton that has greater structural (femoral shaft, femoral neck, tibiae, vertebral body) and apparent material (vertebral body) strength, percent bone ash weight (ulnae), and tibial stiffness. Despite similar body weight to NTG mice, the denser and stiffer bones in G171V mice may represent greater bone formation sensitivity to normal mechanical stimuli resulting in an overadaptation of skeleton to weight-related forces.

KW - Bone ash

KW - High bone mass

KW - LRP5 G171V mutation

UR - http://www.scopus.com/inward/record.url?scp=2942722529&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=2942722529&partnerID=8YFLogxK

U2 - 10.1016/j.bone.2004.02.018

DO - 10.1016/j.bone.2004.02.018

M3 - Article

C2 - 15207752

AN - SCOPUS:2942722529

VL - 35

SP - 162

EP - 169

JO - Bone

JF - Bone

SN - 8756-3282

IS - 1

ER -