Systemic treatment with the sphingosine-1-phosphate analog FTY720 does not improve fracture healing in mice

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Systemic treatment with the sphingosine-1-phosphate analog FTY720 does not improve fracture healing in mice. / Heilmann, Aline; Schinke, Thorsten; Bindl, Ronny; Wehner, Tim; Rapp, Anna; Haffner-Luntzer, Melanie; Liedert, Astrid; Amling, Michael; Ignatius, Anita.

In: J ORTHOP RES, Vol. 31, No. 11, 01.11.2013, p. 1845-50.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

Heilmann, A, Schinke, T, Bindl, R, Wehner, T, Rapp, A, Haffner-Luntzer, M, Liedert, A, Amling, M & Ignatius, A 2013, 'Systemic treatment with the sphingosine-1-phosphate analog FTY720 does not improve fracture healing in mice', J ORTHOP RES, vol. 31, no. 11, pp. 1845-50. https://doi.org/10.1002/jor.22426

APA

Heilmann, A., Schinke, T., Bindl, R., Wehner, T., Rapp, A., Haffner-Luntzer, M., Liedert, A., Amling, M., & Ignatius, A. (2013). Systemic treatment with the sphingosine-1-phosphate analog FTY720 does not improve fracture healing in mice. J ORTHOP RES, 31(11), 1845-50. https://doi.org/10.1002/jor.22426

Vancouver

Bibtex

@article{0db13d2f954c43b7a4336e1d33b0b128,
title = "Systemic treatment with the sphingosine-1-phosphate analog FTY720 does not improve fracture healing in mice",
abstract = "Sphingosine-1-phosphate (S1P) has recently been recognized as a crucial coupling molecule of osteoclast and osteoblast activity provoking osteoanabolic effects. Targeting S1P receptors could, therefore, be a potential strategy to support bone formation in osteopenic diseases or in fracture repair. Here we investigated whether systemic treatment with the S1P analog FTY720 (Fingolimod) could improve fracture healing. Twelve-week-old, female C57BL/6 mice received an osteotomy of the femur, which was stabilized using an external fixator. The mice received a daily subcutaneous injection of either FTY720 (6 mg/kg) or vehicle from the third postoperative day. Fracture healing was evaluated after 10 and 21 days using biomechanical testing, µ-computed tomography, and histomorphometry. Because FTY720 is supposed to influence osteoclast recruitment, osteoclasts were identified in the fracture callus by staining for tartrate resistant acid phosphatase (TRAP). There were no significant differences in callus mechanical properties, tissue composition and osteoclast number between the groups, suggesting that systemically applied FTY720 did not influence bone regeneration in this model of regular fracture healing. Even if further studies should test the potency of FTY720 under unfavorable healing conditions, we conclude that the effect of systemically applied FTY720 on fracture healing might be inferior compared to other anabolic treatments. {\textcopyright} 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1845-1850, 2013.",
keywords = "Acid Phosphatase, Animals, Biomechanical Phenomena, Bone Regeneration, Female, Fracture Healing, Mice, Mice, Inbred C57BL, Osteoclasts, Propylene Glycols, Sphingosine",
author = "Aline Heilmann and Thorsten Schinke and Ronny Bindl and Tim Wehner and Anna Rapp and Melanie Haffner-Luntzer and Astrid Liedert and Michael Amling and Anita Ignatius",
note = "{\textcopyright} 2013 Orthopaedic Research Society.",
year = "2013",
month = nov,
day = "1",
doi = "10.1002/jor.22426",
language = "English",
volume = "31",
pages = "1845--50",
journal = "J ORTHOP RES",
issn = "0736-0266",
publisher = "John Wiley and Sons Inc.",
number = "11",

}

RIS

TY - JOUR

T1 - Systemic treatment with the sphingosine-1-phosphate analog FTY720 does not improve fracture healing in mice

AU - Heilmann, Aline

AU - Schinke, Thorsten

AU - Bindl, Ronny

AU - Wehner, Tim

AU - Rapp, Anna

AU - Haffner-Luntzer, Melanie

AU - Liedert, Astrid

AU - Amling, Michael

AU - Ignatius, Anita

N1 - © 2013 Orthopaedic Research Society.

PY - 2013/11/1

Y1 - 2013/11/1

N2 - Sphingosine-1-phosphate (S1P) has recently been recognized as a crucial coupling molecule of osteoclast and osteoblast activity provoking osteoanabolic effects. Targeting S1P receptors could, therefore, be a potential strategy to support bone formation in osteopenic diseases or in fracture repair. Here we investigated whether systemic treatment with the S1P analog FTY720 (Fingolimod) could improve fracture healing. Twelve-week-old, female C57BL/6 mice received an osteotomy of the femur, which was stabilized using an external fixator. The mice received a daily subcutaneous injection of either FTY720 (6 mg/kg) or vehicle from the third postoperative day. Fracture healing was evaluated after 10 and 21 days using biomechanical testing, µ-computed tomography, and histomorphometry. Because FTY720 is supposed to influence osteoclast recruitment, osteoclasts were identified in the fracture callus by staining for tartrate resistant acid phosphatase (TRAP). There were no significant differences in callus mechanical properties, tissue composition and osteoclast number between the groups, suggesting that systemically applied FTY720 did not influence bone regeneration in this model of regular fracture healing. Even if further studies should test the potency of FTY720 under unfavorable healing conditions, we conclude that the effect of systemically applied FTY720 on fracture healing might be inferior compared to other anabolic treatments. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1845-1850, 2013.

AB - Sphingosine-1-phosphate (S1P) has recently been recognized as a crucial coupling molecule of osteoclast and osteoblast activity provoking osteoanabolic effects. Targeting S1P receptors could, therefore, be a potential strategy to support bone formation in osteopenic diseases or in fracture repair. Here we investigated whether systemic treatment with the S1P analog FTY720 (Fingolimod) could improve fracture healing. Twelve-week-old, female C57BL/6 mice received an osteotomy of the femur, which was stabilized using an external fixator. The mice received a daily subcutaneous injection of either FTY720 (6 mg/kg) or vehicle from the third postoperative day. Fracture healing was evaluated after 10 and 21 days using biomechanical testing, µ-computed tomography, and histomorphometry. Because FTY720 is supposed to influence osteoclast recruitment, osteoclasts were identified in the fracture callus by staining for tartrate resistant acid phosphatase (TRAP). There were no significant differences in callus mechanical properties, tissue composition and osteoclast number between the groups, suggesting that systemically applied FTY720 did not influence bone regeneration in this model of regular fracture healing. Even if further studies should test the potency of FTY720 under unfavorable healing conditions, we conclude that the effect of systemically applied FTY720 on fracture healing might be inferior compared to other anabolic treatments. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1845-1850, 2013.

KW - Acid Phosphatase

KW - Animals

KW - Biomechanical Phenomena

KW - Bone Regeneration

KW - Female

KW - Fracture Healing

KW - Mice

KW - Mice, Inbred C57BL

KW - Osteoclasts

KW - Propylene Glycols

KW - Sphingosine

U2 - 10.1002/jor.22426

DO - 10.1002/jor.22426

M3 - SCORING: Journal article

C2 - 23818033

VL - 31

SP - 1845

EP - 1850

JO - J ORTHOP RES

JF - J ORTHOP RES

SN - 0736-0266

IS - 11

ER -