Assessment of the effect of systemic delivery of sclerostin antibodies on Wnt signaling in distraction osteogenesis
| Autor: | Maria Kotsiopriftis, Reggie C. Hamdy, Frank Rauch, Saber Ghadakzadeh, Dominique Lauzier, Asim M. Makhdom, Mohammad M. Alzahrani |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Osteogenesis Distraction 030209 endocrinology & metabolism Context (language use) Antibodies 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Endocrinology Chondrocytes Downregulation and upregulation Internal medicine medicine Animals Orthopedics and Sports Medicine Tibia Wnt Signaling Pathway Adaptor Proteins Signal Transducing Glycoproteins biology business.industry Wnt signaling pathway General Medicine Fibroblasts Immunohistochemistry 030104 developmental biology chemistry biology.protein Sclerostin Distraction osteogenesis Intercellular Signaling Peptides and Proteins Antibody business |
| Zdroj: | Journal of bone and mineral metabolism. 36(4) |
| ISSN: | 1435-5604 |
| Popis: | Sclerostin is a known inhibitor of the Wnt signaling pathway which is involved in osteogenesis and, when inactivated, stimulates bone formation. To our knowledge, this effect has not been studied in the context of distraction osteogenesis (DO). Tibial DO was conducted on a total of 24 wild-type mice, which were then divided into 2 groups—a saline injection group (control) and an anti-sclerostin (Scl-Ab) injection group (treatment). The mice in the treatment group received 100 mg/kg intravenous injections of the antibody weekly until killing. The 12 mice in each group were subdivided into four time points according to post-osteotomy time of killing—11 days (mid-distraction), 17 days (late distraction), 34 days (mid-consolidation) and 51 days (late consolidation), with 3 mice per subgroup. After killing, the tibia specimens were collected for immunohistochemical analysis. Our results show that the group injected with anti-sclerostin had an earlier peak (day 11) in the distraction phase of the osteogenic molecules involved in the Wnt signaling pathway in comparison to the placebo group. In addition, downregulation of the inhibitors of this pathway was noted in the treatment group when compared with the placebo group. Furthermore, LRP-5 showed a significant increase in expression in the treatment group. Sclerostin inhibition has a significant effect on the DO process through its effect on the Wnt pathway. This effect was evident through the decreased effect of sclerostin on LRP-5 and earlier upregulation of the osteogenic molecules involved in this pathway. |
| Databáze: | OpenAIRE |
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