Endostatin inhibits Callus remodeling during fracture healing in mice
Joerg H Holstein, Bianca Karabin-Kehl, Claudia Scheuer, Patric Garcia, Tina Histing, Christoph Meier, Emanuel Benninger, Michael D Menger & Tim Pohlemann
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abstract
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Information on the impact of endogenous anti-angiogenic factors on
bone repair is limited. The hypothesis of the present study was
endostatin, an endogenous inhibitor of angiogenesis, disturbs
fracture healing. We evaluated this hypothesis in a closed femoral
fracture model studying two groups of mice, one that was treated by
a daily injection of 10 µg recombinant endostatin
subcutaneously (n = 38) and a second one that received
the vehicle for control (n = 37). Histomorphometric
analysis showed a significantly increased callus formation in
endostatin-treated animals at 2 and 5 weeks post-fracture. This was
associated with a significantly higher callus tissue fraction of
cartilage and fibrous tissue at 2 weeks and a significantly higher
fraction of bone at 5 weeks post-fracture. Biomechanical testing
revealed a significantly higher torsional stiffness in the
endostatin group at 2 weeks. For both groups, we could demonstrate
the expression of the endostatin receptor unit integrin alpha5 in
endothelial cells, osteoblasts, osteoclasts, and chondrocytes at 2
weeks. Immunohistochemical fluorescence staining of CD31 showed a
lower number of blood vessels in endostatin-treated animals compared
to controls. The results of the present study indicate endostatin
promotes soft callus formation but inhibits callus remodeling during
fracture healing most probably by an inhibition of angiogenesis.
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citation
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Holstein J H, Karabin-Kehl B, Scheuer C, Garcia P, Histing T, Meier
C, Benninger E, Menger M D, Pohlemann T. Endostatin inhibits Callus
remodeling during fracture healing in mice. J Orthop Res 2013;
31:1579-84.
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type
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journal paper/review (English)
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date of publishing
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30-05-2013
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journal title
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J Orthop Res (31/10)
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ISSN electronic
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1554-527X
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pages
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1579-84
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PubMed
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23720153
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DOI
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10.1002/jor.22401
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