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Human apolipoprotein E isoforms differentially affect bone mass and turnover in vivo.

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Human apolipoprotein E isoforms differentially affect bone mass and turnover in vivo. / Dieckmann, Marco; Beil, Frank Timo; Müller, Brigitte; Bartelt, Alexander; Marshall, Robert Percy; Köhne, Till; Amling, Michael; Ruether, Wolfgang; Cooper, Jackie A; Humphries, Steve E; Herz, Joachim; Niemeier, Andreas.

In: J BONE MINER RES, Vol. 28, No. 2, 2, 2013, p. 236-245.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Dieckmann, M, Beil, FT, Müller, B, Bartelt, A, Marshall, RP, Köhne, T, Amling, M, Ruether, W, Cooper, JA, Humphries, SE, Herz, J & Niemeier, A 2013, 'Human apolipoprotein E isoforms differentially affect bone mass and turnover in vivo.', J BONE MINER RES, vol. 28, no. 2, 2, pp. 236-245. https://doi.org/10.1002/jbmr.1757

APA

Dieckmann, M., Beil, F. T., Müller, B., Bartelt, A., Marshall, R. P., Köhne, T., Amling, M., Ruether, W., Cooper, J. A., Humphries, S. E., Herz, J., & Niemeier, A. (2013). Human apolipoprotein E isoforms differentially affect bone mass and turnover in vivo. J BONE MINER RES, 28(2), 236-245. [2]. https://doi.org/10.1002/jbmr.1757

Vancouver

Dieckmann M, Beil FT, Müller B, Bartelt A, Marshall RP, Köhne T et al. Human apolipoprotein E isoforms differentially affect bone mass and turnover in vivo. J BONE MINER RES. 2013;28(2):236-245. 2. https://doi.org/10.1002/jbmr.1757

Bibtex

@article{53788463891c47709c289dbd2f444274,
title = "Human apolipoprotein E isoforms differentially affect bone mass and turnover in vivo.",
abstract = "The primary role of apolipoprotein E (apoE) is to mediate the cellular uptake of lipoproteins. However, a new role for apoE as a regulator of bone metabolism in mice has recently been established. In contrast to mice, the human APOE gene is characterized by three common isoforms APOE ε2, ε3, and ε4 that result in different metabolic properties of the apoE isoforms, but it remains controversial whether the APOE polymorphism influences bone traits in humans. To clarify this, we investigated bone phenotypes of apoE knock-in (k.i.) mice, which express one human isoform each (apoE2 k.i., apoE3 k.i., apoE4 k.i.) in place of the mouse apoE. Analysis of 12-week-old female k.i. mice revealed increased levels of biochemical bone formation and resorption markers in apoE2 k.i. animals as compared to apoE3 k.i. and apoE4 k.i., with a reduced osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) ratio in apoE2 k.i., indicating increased turnover with prevailing resorption in apoE2 k.i. Accordingly, histomorphometric and micro-computed tomography (µCT) analyses demonstrated significantly lower trabecular bone mass in apoE2 than in apoE3 and apoE4 k.i. animals, which was reflected by a significant reduction of lumbar vertebrae maximum force resistance. Unlike trabecular bone, femoral cortical thickness, and stability was not differentially affected by the apoE isoforms. To extend these observations to the human situation, plasma from middle-aged healthy men homozygous for ε2/ε2, ε3/ε3, and ε4/ε4 (n = 21, n = 80, n = 55, respectively) was analyzed with regard to bone turnover markers. In analogy to apoE2 k.i. mice, a lower OPG/RANKL ratio was observed in the serum of ε2/ε2 carriers as compared to ε3/ε3 and ε4/ε4 individuals (p = 0.02 for ε2/ε2 versus ε4/ε4). In conclusion, the current data strongly underline the general importance of apoE as a regulator of bone metabolism and identifies the APOE ε2 allele as a potential genetic risk factor for low trabecular bone mass and vertebral fractures in humans.",
keywords = "Animals, Humans, Male, Female, Middle Aged, Mice, Mice, Inbred C57BL, Homozygote, Mice, Transgenic, Biomechanics, Organ Size, Gene Knock-In Techniques, Bone Remodeling/*physiology, Biological Markers/metabolism, Osteogenesis, Bone Density/physiology, Apolipoprotein E2/blood/genetics, Apolipoprotein E3/genetics/metabolism, Apolipoprotein E4/genetics/metabolism, Apolipoproteins E/genetics/*metabolism, Bone and Bones/*anatomy & histology/*physiology, Femur/physiology, Lumbar Vertebrae/physiology, Osteoprotegerin/blood/metabolism, Protein Isoforms, RANK Ligand/blood/metabolism, Animals, Humans, Male, Female, Middle Aged, Mice, Mice, Inbred C57BL, Homozygote, Mice, Transgenic, Biomechanics, Organ Size, Gene Knock-In Techniques, Bone Remodeling/*physiology, Biological Markers/metabolism, Osteogenesis, Bone Density/physiology, Apolipoprotein E2/blood/genetics, Apolipoprotein E3/genetics/metabolism, Apolipoprotein E4/genetics/metabolism, Apolipoproteins E/genetics/*metabolism, Bone and Bones/*anatomy & histology/*physiology, Femur/physiology, Lumbar Vertebrae/physiology, Osteoprotegerin/blood/metabolism, Protein Isoforms, RANK Ligand/blood/metabolism",
author = "Marco Dieckmann and Beil, {Frank Timo} and Brigitte M{\"u}ller and Alexander Bartelt and Marshall, {Robert Percy} and Till K{\"o}hne and Michael Amling and Wolfgang Ruether and Cooper, {Jackie A} and Humphries, {Steve E} and Joachim Herz and Andreas Niemeier",
note = "Copyright {\textcopyright} 2013 American Society for Bone and Mineral Research.",
year = "2013",
doi = "10.1002/jbmr.1757",
language = "English",
volume = "28",
pages = "236--245",
journal = "J BONE MINER RES",
issn = "0884-0431",
publisher = "Wiley-Blackwell",
number = "2",

}

RIS

TY - JOUR

T1 - Human apolipoprotein E isoforms differentially affect bone mass and turnover in vivo.

AU - Dieckmann, Marco

AU - Beil, Frank Timo

AU - Müller, Brigitte

AU - Bartelt, Alexander

AU - Marshall, Robert Percy

AU - Köhne, Till

AU - Amling, Michael

AU - Ruether, Wolfgang

AU - Cooper, Jackie A

AU - Humphries, Steve E

AU - Herz, Joachim

AU - Niemeier, Andreas

N1 - Copyright © 2013 American Society for Bone and Mineral Research.

PY - 2013

Y1 - 2013

N2 - The primary role of apolipoprotein E (apoE) is to mediate the cellular uptake of lipoproteins. However, a new role for apoE as a regulator of bone metabolism in mice has recently been established. In contrast to mice, the human APOE gene is characterized by three common isoforms APOE ε2, ε3, and ε4 that result in different metabolic properties of the apoE isoforms, but it remains controversial whether the APOE polymorphism influences bone traits in humans. To clarify this, we investigated bone phenotypes of apoE knock-in (k.i.) mice, which express one human isoform each (apoE2 k.i., apoE3 k.i., apoE4 k.i.) in place of the mouse apoE. Analysis of 12-week-old female k.i. mice revealed increased levels of biochemical bone formation and resorption markers in apoE2 k.i. animals as compared to apoE3 k.i. and apoE4 k.i., with a reduced osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) ratio in apoE2 k.i., indicating increased turnover with prevailing resorption in apoE2 k.i. Accordingly, histomorphometric and micro-computed tomography (µCT) analyses demonstrated significantly lower trabecular bone mass in apoE2 than in apoE3 and apoE4 k.i. animals, which was reflected by a significant reduction of lumbar vertebrae maximum force resistance. Unlike trabecular bone, femoral cortical thickness, and stability was not differentially affected by the apoE isoforms. To extend these observations to the human situation, plasma from middle-aged healthy men homozygous for ε2/ε2, ε3/ε3, and ε4/ε4 (n = 21, n = 80, n = 55, respectively) was analyzed with regard to bone turnover markers. In analogy to apoE2 k.i. mice, a lower OPG/RANKL ratio was observed in the serum of ε2/ε2 carriers as compared to ε3/ε3 and ε4/ε4 individuals (p = 0.02 for ε2/ε2 versus ε4/ε4). In conclusion, the current data strongly underline the general importance of apoE as a regulator of bone metabolism and identifies the APOE ε2 allele as a potential genetic risk factor for low trabecular bone mass and vertebral fractures in humans.

AB - The primary role of apolipoprotein E (apoE) is to mediate the cellular uptake of lipoproteins. However, a new role for apoE as a regulator of bone metabolism in mice has recently been established. In contrast to mice, the human APOE gene is characterized by three common isoforms APOE ε2, ε3, and ε4 that result in different metabolic properties of the apoE isoforms, but it remains controversial whether the APOE polymorphism influences bone traits in humans. To clarify this, we investigated bone phenotypes of apoE knock-in (k.i.) mice, which express one human isoform each (apoE2 k.i., apoE3 k.i., apoE4 k.i.) in place of the mouse apoE. Analysis of 12-week-old female k.i. mice revealed increased levels of biochemical bone formation and resorption markers in apoE2 k.i. animals as compared to apoE3 k.i. and apoE4 k.i., with a reduced osteoprotegerin (OPG)/receptor activator of NF-κB ligand (RANKL) ratio in apoE2 k.i., indicating increased turnover with prevailing resorption in apoE2 k.i. Accordingly, histomorphometric and micro-computed tomography (µCT) analyses demonstrated significantly lower trabecular bone mass in apoE2 than in apoE3 and apoE4 k.i. animals, which was reflected by a significant reduction of lumbar vertebrae maximum force resistance. Unlike trabecular bone, femoral cortical thickness, and stability was not differentially affected by the apoE isoforms. To extend these observations to the human situation, plasma from middle-aged healthy men homozygous for ε2/ε2, ε3/ε3, and ε4/ε4 (n = 21, n = 80, n = 55, respectively) was analyzed with regard to bone turnover markers. In analogy to apoE2 k.i. mice, a lower OPG/RANKL ratio was observed in the serum of ε2/ε2 carriers as compared to ε3/ε3 and ε4/ε4 individuals (p = 0.02 for ε2/ε2 versus ε4/ε4). In conclusion, the current data strongly underline the general importance of apoE as a regulator of bone metabolism and identifies the APOE ε2 allele as a potential genetic risk factor for low trabecular bone mass and vertebral fractures in humans.

KW - Animals

KW - Humans

KW - Male

KW - Female

KW - Middle Aged

KW - Mice

KW - Mice, Inbred C57BL

KW - Homozygote

KW - Mice, Transgenic

KW - Biomechanics

KW - Organ Size

KW - Gene Knock-In Techniques

KW - Bone Remodeling/physiology

KW - Biological Markers/metabolism

KW - Osteogenesis

KW - Bone Density/physiology

KW - Apolipoprotein E2/blood/genetics

KW - Apolipoprotein E3/genetics/metabolism

KW - Apolipoprotein E4/genetics/metabolism

KW - Apolipoproteins E/genetics/metabolism

KW - Bone and Bones/anatomy & histology/physiology

KW - Femur/physiology

KW - Lumbar Vertebrae/physiology

KW - Osteoprotegerin/blood/metabolism

KW - Protein Isoforms

KW - RANK Ligand/blood/metabolism

KW - Animals

KW - Humans

KW - Male

KW - Female

KW - Middle Aged

KW - Mice

KW - Mice, Inbred C57BL

KW - Homozygote

KW - Mice, Transgenic

KW - Biomechanics

KW - Organ Size

KW - Gene Knock-In Techniques

KW - Bone Remodeling/physiology

KW - Biological Markers/metabolism

KW - Osteogenesis

KW - Bone Density/physiology

KW - Apolipoprotein E2/blood/genetics

KW - Apolipoprotein E3/genetics/metabolism

KW - Apolipoprotein E4/genetics/metabolism

KW - Apolipoproteins E/genetics/metabolism

KW - Bone and Bones/anatomy & histology/physiology

KW - Femur/physiology

KW - Lumbar Vertebrae/physiology

KW - Osteoprotegerin/blood/metabolism

KW - Protein Isoforms

KW - RANK Ligand/blood/metabolism

U2 - 10.1002/jbmr.1757

DO - 10.1002/jbmr.1757

M3 - SCORING: Journal article

C2 - 22991192

VL - 28

SP - 236

EP - 245

JO - J BONE MINER RES

JF - J BONE MINER RES

SN - 0884-0431

IS - 2

M1 - 2

ER -