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Osteoblast-specific Krm2 overexpression and Lrp5 deficiency have different effects on fracture healing in mice

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Osteoblast-specific Krm2 overexpression and Lrp5 deficiency have different effects on fracture healing in mice. / Liedert, Astrid; Röntgen, Viktoria; Schinke, Thorsten; Benisch, Peggy; Ebert, Regina; Jakob, Franz; Klein-Hitpass, Ludger; Lennerz, Jochen K; Amling, Michael; Ignatius, Anita.

In: PLOS ONE, Vol. 9, No. 7, 25.07.2014, p. e103250.

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

Harvard

Liedert, A, Röntgen, V, Schinke, T, Benisch, P, Ebert, R, Jakob, F, Klein-Hitpass, L, Lennerz, JK, Amling, M & Ignatius, A 2014, 'Osteoblast-specific Krm2 overexpression and Lrp5 deficiency have different effects on fracture healing in mice', PLOS ONE, vol. 9, no. 7, pp. e103250. https://doi.org/10.1371/journal.pone.0103250

APA

Liedert, A., Röntgen, V., Schinke, T., Benisch, P., Ebert, R., Jakob, F., Klein-Hitpass, L., Lennerz, J. K., Amling, M., & Ignatius, A. (2014). Osteoblast-specific Krm2 overexpression and Lrp5 deficiency have different effects on fracture healing in mice. PLOS ONE, 9(7), e103250. https://doi.org/10.1371/journal.pone.0103250

Vancouver

Liedert A, Röntgen V, Schinke T, Benisch P, Ebert R, Jakob F et al. Osteoblast-specific Krm2 overexpression and Lrp5 deficiency have different effects on fracture healing in mice. PLOS ONE. 2014 Jul 25;9(7):e103250. https://doi.org/10.1371/journal.pone.0103250

Bibtex

@article{3bc36cf1ca31431b84796e2171dbb447,
title = "Osteoblast-specific Krm2 overexpression and Lrp5 deficiency have different effects on fracture healing in mice",
abstract = "The canonical Wnt/β-catenin pathway plays a key role in the regulation of bone remodeling in mice and humans. Two transmembrane proteins that are involved in decreasing the activity of this pathway by binding to extracellular antagonists, such as Dickkopf 1 (Dkk1), are the low-density lipoprotein receptor related protein 5 (Lrp5) and Kremen 2 (Krm2). Lrp 5 deficiency (Lrp5-/-) as well as osteoblast-specific overexpression of Krm2 in mice (Col1a1-Krm2) result in severe osteoporosis occurring at young age. In this study, we analyzed the influence of Lrp5 deficiency and osteoblast-specific overexpression of Krm2 on fracture healing in mice using flexible and semi-rigid fracture fixation. We demonstrated that fracture healing was highly impaired in both mouse genotypes, but that impairment was more severe in Col1a1-Krm2 than in Lrp5-/- mice and particularly evident in mice in which the more flexible fixation was used. Bone formation was more reduced in Col1a1-Krm2 than in Lrp5-/- mice, whereas osteoclast number was similarly increased in both genotypes in comparison with wild-type mice. Using microarray analysis we identified reduced expression of genes mainly involved in osteogenesis that seemed to be responsible for the observed stronger impairment of healing in Col1a1-Krm2 mice. In line with these findings, we detected decreased expression of sphingomyelin phosphodiesterase 3 (Smpd3) and less active β-catenin in the calli of Col1a1-Krm2 mice. Since Krm2 seems to play a significant role in regulating bone formation during fracture healing, antagonizing KRM2 might be a therapeutic option to improve fracture healing under compromised conditions, such as osteoporosis.",
author = "Astrid Liedert and Viktoria R{\"o}ntgen and Thorsten Schinke and Peggy Benisch and Regina Ebert and Franz Jakob and Ludger Klein-Hitpass and Lennerz, {Jochen K} and Michael Amling and Anita Ignatius",
year = "2014",
month = jul,
day = "25",
doi = "10.1371/journal.pone.0103250",
language = "English",
volume = "9",
pages = "e103250",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "7",

}

RIS

TY - JOUR

T1 - Osteoblast-specific Krm2 overexpression and Lrp5 deficiency have different effects on fracture healing in mice

AU - Liedert, Astrid

AU - Röntgen, Viktoria

AU - Schinke, Thorsten

AU - Benisch, Peggy

AU - Ebert, Regina

AU - Jakob, Franz

AU - Klein-Hitpass, Ludger

AU - Lennerz, Jochen K

AU - Amling, Michael

AU - Ignatius, Anita

PY - 2014/7/25

Y1 - 2014/7/25

N2 - The canonical Wnt/β-catenin pathway plays a key role in the regulation of bone remodeling in mice and humans. Two transmembrane proteins that are involved in decreasing the activity of this pathway by binding to extracellular antagonists, such as Dickkopf 1 (Dkk1), are the low-density lipoprotein receptor related protein 5 (Lrp5) and Kremen 2 (Krm2). Lrp 5 deficiency (Lrp5-/-) as well as osteoblast-specific overexpression of Krm2 in mice (Col1a1-Krm2) result in severe osteoporosis occurring at young age. In this study, we analyzed the influence of Lrp5 deficiency and osteoblast-specific overexpression of Krm2 on fracture healing in mice using flexible and semi-rigid fracture fixation. We demonstrated that fracture healing was highly impaired in both mouse genotypes, but that impairment was more severe in Col1a1-Krm2 than in Lrp5-/- mice and particularly evident in mice in which the more flexible fixation was used. Bone formation was more reduced in Col1a1-Krm2 than in Lrp5-/- mice, whereas osteoclast number was similarly increased in both genotypes in comparison with wild-type mice. Using microarray analysis we identified reduced expression of genes mainly involved in osteogenesis that seemed to be responsible for the observed stronger impairment of healing in Col1a1-Krm2 mice. In line with these findings, we detected decreased expression of sphingomyelin phosphodiesterase 3 (Smpd3) and less active β-catenin in the calli of Col1a1-Krm2 mice. Since Krm2 seems to play a significant role in regulating bone formation during fracture healing, antagonizing KRM2 might be a therapeutic option to improve fracture healing under compromised conditions, such as osteoporosis.

AB - The canonical Wnt/β-catenin pathway plays a key role in the regulation of bone remodeling in mice and humans. Two transmembrane proteins that are involved in decreasing the activity of this pathway by binding to extracellular antagonists, such as Dickkopf 1 (Dkk1), are the low-density lipoprotein receptor related protein 5 (Lrp5) and Kremen 2 (Krm2). Lrp 5 deficiency (Lrp5-/-) as well as osteoblast-specific overexpression of Krm2 in mice (Col1a1-Krm2) result in severe osteoporosis occurring at young age. In this study, we analyzed the influence of Lrp5 deficiency and osteoblast-specific overexpression of Krm2 on fracture healing in mice using flexible and semi-rigid fracture fixation. We demonstrated that fracture healing was highly impaired in both mouse genotypes, but that impairment was more severe in Col1a1-Krm2 than in Lrp5-/- mice and particularly evident in mice in which the more flexible fixation was used. Bone formation was more reduced in Col1a1-Krm2 than in Lrp5-/- mice, whereas osteoclast number was similarly increased in both genotypes in comparison with wild-type mice. Using microarray analysis we identified reduced expression of genes mainly involved in osteogenesis that seemed to be responsible for the observed stronger impairment of healing in Col1a1-Krm2 mice. In line with these findings, we detected decreased expression of sphingomyelin phosphodiesterase 3 (Smpd3) and less active β-catenin in the calli of Col1a1-Krm2 mice. Since Krm2 seems to play a significant role in regulating bone formation during fracture healing, antagonizing KRM2 might be a therapeutic option to improve fracture healing under compromised conditions, such as osteoporosis.

U2 - 10.1371/journal.pone.0103250

DO - 10.1371/journal.pone.0103250

M3 - SCORING: Journal article

C2 - 25061805

VL - 9

SP - e103250

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 7

ER -