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, Jahrgang 31, Nr. 11, 01.11.2013, S. 1845-50.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -