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Antagonizing midkine accelerates fracture healing in mice by enhanced bone formation in the fracture callus

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Antagonizing midkine accelerates fracture healing in mice by enhanced bone formation in the fracture callus. / Haffner-Luntzer, Melanie; Heilmann, Aline; Rapp, Anna Elise; Roessler, Robin; Schinke, Thorsten; Amling, Michael; Ignatius, Anita; Liedert, Astrid.

In: BRIT J PHARMACOL, Vol. 173, No. 14, 07.2016, p. 2237-49.

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

Harvard

Haffner-Luntzer, M, Heilmann, A, Rapp, AE, Roessler, R, Schinke, T, Amling, M, Ignatius, A & Liedert, A 2016, 'Antagonizing midkine accelerates fracture healing in mice by enhanced bone formation in the fracture callus', BRIT J PHARMACOL, vol. 173, no. 14, pp. 2237-49. https://doi.org/10.1111/bph.13503

APA

Haffner-Luntzer, M., Heilmann, A., Rapp, A. E., Roessler, R., Schinke, T., Amling, M., Ignatius, A., & Liedert, A. (2016). Antagonizing midkine accelerates fracture healing in mice by enhanced bone formation in the fracture callus. BRIT J PHARMACOL, 173(14), 2237-49. https://doi.org/10.1111/bph.13503

Vancouver

Haffner-Luntzer M, Heilmann A, Rapp AE, Roessler R, Schinke T, Amling M et al. Antagonizing midkine accelerates fracture healing in mice by enhanced bone formation in the fracture callus. BRIT J PHARMACOL. 2016 Jul;173(14):2237-49. https://doi.org/10.1111/bph.13503

Bibtex

@article{c17f2bcfe63344019e847f20c4cc89ae,
title = "Antagonizing midkine accelerates fracture healing in mice by enhanced bone formation in the fracture callus",
abstract = "BACKGROUND AND PURPOSE: Previous findings suggest that the growth and differentiation factor midkine (Mdk) is a negative regulator of osteoblast activity and bone formation, thereby raising the possibility that a specific Mdk antagonist might improve bone formation during fracture healing.EXPERIMENTAL APPROACH: In the present study, we investigated the effects of a monoclonal anti-Mdk antibody (Mdk-Ab) on bone healing using a standardized femur osteotomy model in mice. Additional in vitro experiments using chondroprogenitor and preosteoblastic cells were conducted to analyse the effects of recombinant Mdk and Mdk-Ab on differentiation markers and potential binding partners in these cells.KEY RESULTS: We demonstrated that treatment with Mdk-Ab accelerated bone healing in mice based on increased bone formation in the fracture callus. In vitro experiments using preosteoblastic cells showed that Mdk-Ab treatment abolished the Mdk-induced negative effects on the expression of osteogenic markers and Wnt/β-catenin target proteins, whereas the differentiation of chondroprogenitor cells was unaffected. Phosphorylation analyses revealed an important role for the low-density lipoproteinLDL receptor-related protein 6 in Mdk signalling in osteoblasts.CONCLUSIONS AND IMPLICATIONS: We conclude that Mdk-Ab treatment may be a potential novel therapeutic strategy to enhance fracture healing in patients with orthopaedic complications such as delayed healing or non-union formation.",
keywords = "Journal Article",
author = "Melanie Haffner-Luntzer and Aline Heilmann and Rapp, {Anna Elise} and Robin Roessler and Thorsten Schinke and Michael Amling and Anita Ignatius and Astrid Liedert",
note = "{\textcopyright} 2016 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.",
year = "2016",
month = jul,
doi = "10.1111/bph.13503",
language = "English",
volume = "173",
pages = "2237--49",
journal = "BRIT J PHARMACOL",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "14",

}

RIS

TY - JOUR

T1 - Antagonizing midkine accelerates fracture healing in mice by enhanced bone formation in the fracture callus

AU - Haffner-Luntzer, Melanie

AU - Heilmann, Aline

AU - Rapp, Anna Elise

AU - Roessler, Robin

AU - Schinke, Thorsten

AU - Amling, Michael

AU - Ignatius, Anita

AU - Liedert, Astrid

N1 - © 2016 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

PY - 2016/7

Y1 - 2016/7

N2 - BACKGROUND AND PURPOSE: Previous findings suggest that the growth and differentiation factor midkine (Mdk) is a negative regulator of osteoblast activity and bone formation, thereby raising the possibility that a specific Mdk antagonist might improve bone formation during fracture healing.EXPERIMENTAL APPROACH: In the present study, we investigated the effects of a monoclonal anti-Mdk antibody (Mdk-Ab) on bone healing using a standardized femur osteotomy model in mice. Additional in vitro experiments using chondroprogenitor and preosteoblastic cells were conducted to analyse the effects of recombinant Mdk and Mdk-Ab on differentiation markers and potential binding partners in these cells.KEY RESULTS: We demonstrated that treatment with Mdk-Ab accelerated bone healing in mice based on increased bone formation in the fracture callus. In vitro experiments using preosteoblastic cells showed that Mdk-Ab treatment abolished the Mdk-induced negative effects on the expression of osteogenic markers and Wnt/β-catenin target proteins, whereas the differentiation of chondroprogenitor cells was unaffected. Phosphorylation analyses revealed an important role for the low-density lipoproteinLDL receptor-related protein 6 in Mdk signalling in osteoblasts.CONCLUSIONS AND IMPLICATIONS: We conclude that Mdk-Ab treatment may be a potential novel therapeutic strategy to enhance fracture healing in patients with orthopaedic complications such as delayed healing or non-union formation.

AB - BACKGROUND AND PURPOSE: Previous findings suggest that the growth and differentiation factor midkine (Mdk) is a negative regulator of osteoblast activity and bone formation, thereby raising the possibility that a specific Mdk antagonist might improve bone formation during fracture healing.EXPERIMENTAL APPROACH: In the present study, we investigated the effects of a monoclonal anti-Mdk antibody (Mdk-Ab) on bone healing using a standardized femur osteotomy model in mice. Additional in vitro experiments using chondroprogenitor and preosteoblastic cells were conducted to analyse the effects of recombinant Mdk and Mdk-Ab on differentiation markers and potential binding partners in these cells.KEY RESULTS: We demonstrated that treatment with Mdk-Ab accelerated bone healing in mice based on increased bone formation in the fracture callus. In vitro experiments using preosteoblastic cells showed that Mdk-Ab treatment abolished the Mdk-induced negative effects on the expression of osteogenic markers and Wnt/β-catenin target proteins, whereas the differentiation of chondroprogenitor cells was unaffected. Phosphorylation analyses revealed an important role for the low-density lipoproteinLDL receptor-related protein 6 in Mdk signalling in osteoblasts.CONCLUSIONS AND IMPLICATIONS: We conclude that Mdk-Ab treatment may be a potential novel therapeutic strategy to enhance fracture healing in patients with orthopaedic complications such as delayed healing or non-union formation.

KW - Journal Article

U2 - 10.1111/bph.13503

DO - 10.1111/bph.13503

M3 - SCORING: Journal article

C2 - 27111560

VL - 173

SP - 2237

EP - 2249

JO - BRIT J PHARMACOL

JF - BRIT J PHARMACOL

SN - 0007-1188

IS - 14

ER -