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Midkine-deficiency delays chondrogenesis during the early phase of fracture healing in mice

Standard

Midkine-deficiency delays chondrogenesis during the early phase of fracture healing in mice. / Haffner-Luntzer, Melanie; Heilmann, Aline; Rapp, Anna Elise; Beie, Simon; Schinke, Thorsten; Amling, Michael; Ignatius, Anita; Liedert, Astrid.

In: PLOS ONE, Vol. 9, No. 12, 31.12.2014, p. e116282.

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

Harvard

Haffner-Luntzer, M, Heilmann, A, Rapp, AE, Beie, S, Schinke, T, Amling, M, Ignatius, A & Liedert, A 2014, 'Midkine-deficiency delays chondrogenesis during the early phase of fracture healing in mice', PLOS ONE, vol. 9, no. 12, pp. e116282. https://doi.org/10.1371/journal.pone.0116282

APA

Haffner-Luntzer, M., Heilmann, A., Rapp, A. E., Beie, S., Schinke, T., Amling, M., Ignatius, A., & Liedert, A. (2014). Midkine-deficiency delays chondrogenesis during the early phase of fracture healing in mice. PLOS ONE, 9(12), e116282. https://doi.org/10.1371/journal.pone.0116282

Vancouver

Haffner-Luntzer M, Heilmann A, Rapp AE, Beie S, Schinke T, Amling M et al. Midkine-deficiency delays chondrogenesis during the early phase of fracture healing in mice. PLOS ONE. 2014 Dec 31;9(12):e116282. https://doi.org/10.1371/journal.pone.0116282

Bibtex

@article{12717f13f6de43398993cc83cd7ad147,
title = "Midkine-deficiency delays chondrogenesis during the early phase of fracture healing in mice",
abstract = "The growth and differentiation factor midkine (Mdk) plays an important role in bone development and remodeling. Mdk-deficient mice display a high bone mass phenotype when aged 12 and 18 months. Furthermore, Mdk has been identified as a negative regulator of mechanically induced bone formation and it induces pro-chondrogenic, pro-angiogenic and pro-inflammatory effects. Together with the finding that Mdk is expressed in chondrocytes during fracture healing, we hypothesized that Mdk could play a complex role in endochondral ossification during the bone healing process. Femoral osteotomies stabilized using an external fixator were created in wildtype and Mdk-deficient mice. Fracture healing was evaluated 4, 10, 21 and 28 days after surgery using 3-point-bending, micro-computed tomography, histology and immunohistology. We demonstrated that Mdk-deficient mice displayed delayed chondrogenesis during the early phase of fracture healing as well as significantly decreased flexural rigidity and moment of inertia of the fracture callus 21 days after fracture. Mdk-deficiency diminished beta-catenin expression in chondrocytes and delayed presence of macrophages during early fracture healing. We also investigated the impact of Mdk knockdown using siRNA on ATDC5 chondroprogenitor cells in vitro. Knockdown of Mdk expression resulted in a decrease of beta-catenin and chondrogenic differentiation-related matrix proteins, suggesting that delayed chondrogenesis during fracture healing in Mdk-deficient mice may be due to a cell-autonomous mechanism involving reduced beta-catenin signaling. Our results demonstrated that Mdk plays a crucial role in the early inflammation phase and during the development of cartilaginous callus in the fracture healing process.",
author = "Melanie Haffner-Luntzer and Aline Heilmann and Rapp, {Anna Elise} and Simon Beie and Thorsten Schinke and Michael Amling and Anita Ignatius and Astrid Liedert",
year = "2014",
month = dec,
day = "31",
doi = "10.1371/journal.pone.0116282",
language = "English",
volume = "9",
pages = "e116282",
journal = "PLOS ONE",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "12",

}

RIS

TY - JOUR

T1 - Midkine-deficiency delays chondrogenesis during the early phase of fracture healing in mice

AU - Haffner-Luntzer, Melanie

AU - Heilmann, Aline

AU - Rapp, Anna Elise

AU - Beie, Simon

AU - Schinke, Thorsten

AU - Amling, Michael

AU - Ignatius, Anita

AU - Liedert, Astrid

PY - 2014/12/31

Y1 - 2014/12/31

N2 - The growth and differentiation factor midkine (Mdk) plays an important role in bone development and remodeling. Mdk-deficient mice display a high bone mass phenotype when aged 12 and 18 months. Furthermore, Mdk has been identified as a negative regulator of mechanically induced bone formation and it induces pro-chondrogenic, pro-angiogenic and pro-inflammatory effects. Together with the finding that Mdk is expressed in chondrocytes during fracture healing, we hypothesized that Mdk could play a complex role in endochondral ossification during the bone healing process. Femoral osteotomies stabilized using an external fixator were created in wildtype and Mdk-deficient mice. Fracture healing was evaluated 4, 10, 21 and 28 days after surgery using 3-point-bending, micro-computed tomography, histology and immunohistology. We demonstrated that Mdk-deficient mice displayed delayed chondrogenesis during the early phase of fracture healing as well as significantly decreased flexural rigidity and moment of inertia of the fracture callus 21 days after fracture. Mdk-deficiency diminished beta-catenin expression in chondrocytes and delayed presence of macrophages during early fracture healing. We also investigated the impact of Mdk knockdown using siRNA on ATDC5 chondroprogenitor cells in vitro. Knockdown of Mdk expression resulted in a decrease of beta-catenin and chondrogenic differentiation-related matrix proteins, suggesting that delayed chondrogenesis during fracture healing in Mdk-deficient mice may be due to a cell-autonomous mechanism involving reduced beta-catenin signaling. Our results demonstrated that Mdk plays a crucial role in the early inflammation phase and during the development of cartilaginous callus in the fracture healing process.

AB - The growth and differentiation factor midkine (Mdk) plays an important role in bone development and remodeling. Mdk-deficient mice display a high bone mass phenotype when aged 12 and 18 months. Furthermore, Mdk has been identified as a negative regulator of mechanically induced bone formation and it induces pro-chondrogenic, pro-angiogenic and pro-inflammatory effects. Together with the finding that Mdk is expressed in chondrocytes during fracture healing, we hypothesized that Mdk could play a complex role in endochondral ossification during the bone healing process. Femoral osteotomies stabilized using an external fixator were created in wildtype and Mdk-deficient mice. Fracture healing was evaluated 4, 10, 21 and 28 days after surgery using 3-point-bending, micro-computed tomography, histology and immunohistology. We demonstrated that Mdk-deficient mice displayed delayed chondrogenesis during the early phase of fracture healing as well as significantly decreased flexural rigidity and moment of inertia of the fracture callus 21 days after fracture. Mdk-deficiency diminished beta-catenin expression in chondrocytes and delayed presence of macrophages during early fracture healing. We also investigated the impact of Mdk knockdown using siRNA on ATDC5 chondroprogenitor cells in vitro. Knockdown of Mdk expression resulted in a decrease of beta-catenin and chondrogenic differentiation-related matrix proteins, suggesting that delayed chondrogenesis during fracture healing in Mdk-deficient mice may be due to a cell-autonomous mechanism involving reduced beta-catenin signaling. Our results demonstrated that Mdk plays a crucial role in the early inflammation phase and during the development of cartilaginous callus in the fracture healing process.

U2 - 10.1371/journal.pone.0116282

DO - 10.1371/journal.pone.0116282

M3 - SCORING: Journal article

C2 - 25551381

VL - 9

SP - e116282

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 12

ER -