Expression of osteotropic growth factors and growth hormone receptor in a canine distraction osteogenesis model |
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Authors: | Lars FH Theyse Marja A Oosterlaken-Dijksterhuis Jaap van Doorn Maarten Terlou Jan A Mol George Voorhout Herman AW Hazewinkel |
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Institution: | (1) Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, P.O. Box 80.154, NL-3508, TD, Utrecht, The Netherlands.;(2) Department of Metabolic and Endocrine Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands;(3) Department of Image Processing and Design, Faculty of Biology, Utrecht University, Utrecht, The Netherlands;(4) Division of Diagnostic Imaging, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands |
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Abstract: | Osteotropic growth factors play an important role in bone metabolism. Nevertheless, knowledge about their expression in relation
to distraction osteogenesis remains limited. The aim of the present study was to determine the expression of growth hormone
(GH), growth hormone receptor (GHR), insulin-like growth factor I (IGF-I), insulin-like growth factor II (IGF-II), and bone
morphogenetic protein 2 (BMP-2) in distraction-induced bone regeneration. Expression of these factors was assessed during
the consolidation phase, comparing distraction osteogenesis with osteotomy-induced bone formation. Real-time PCR was performed
as a semiquantitative measurement of mRNA, and the relative expression levels of these factors were determined. In addition,
plasma GH profiles and plasma concentrations of IGF-I, IGF-II, and insulin-like growth factor-binding protein 4 and -6 (IGFBP-4
and -6) were measured to assess their potential systemic role during bone formation. Expression of GHR, IGF-I, and BMP-2 had
significantly increased in comparison with the expression of these factors in mature bone. Expression of GHR was significantly
higher in distraction-induced bone regenerate than in osteotomy-induced bone. No significant differences were found for the
expression of IGF-I and BMP-2 between distraction and osteotomy. Plasma concentrations of GH, IGF-I, IGF-II, IGFBP-4, and
IGFBP-6 did not demonstrate any significant differences between treatment groups and controls. Upregulation of GHR expression
in distraction osteogenesis may enhance sensitivity to endogenous systemic GH and thus promote consolidation of the regenerated
bone. Changes in the systemic osteotropic growth factors GH, IGF-I, IGF-II, IGFBP-4, and IGFBP-6 do not seem to be of importance
during distraction osteogenesis. |
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Keywords: | distraction osteogenesis growth hormone receptor IGF-I BMP-2 real-time PCR |
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