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Author |
Burgers, T.A.; Vivanco, J.F.; Zahatnansky, J.; Moren, A.J.V.; Mason, J.J.; Williams, B.O. |
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Title |
Mice with a heterozygous Lrp6 deletion have impaired fracture healing |
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Year |
2016 |
Publication |
Bone Research |
Abbreviated Journal |
Bone Res. |
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Volume |
4 |
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9 pp |
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Abstract |
Bone fracture non-unions, the failure of a fracture to heal, occur in 10%-20% of fractures and are a costly and debilitating clinical problem. The Wnt/beta-catenin pathway is critical in bone development and fracture healing. Polymorphisms of linking low-density lipoprotein receptor-related protein 6 (LRP6), a Wnt-binding receptor, have been associated with decreased bone mineral density and fragility fractures, although this remains controversial. Mice with a homozygous deletion of Lrp6 have severe skeletal abnormalities and are not viable, whereas mice with a heterozygous deletion have a combinatory effect with Lrp5 to decrease bone mineral density. As fracture healing closely models embryonic skeletal development, we investigated the process of fracture healing in mice heterozygous for Lrp6 (Lrp6(+/-)) and hypothesized that the heterozygous deletion of Lrp6 would impair fracture healing. Mid-diaphyseal femur fractures were induced in Lrp6(+/-) mice and wild-type controls (Lrp6(+/+)). Fractures were analyzed using micro-computed tomography (mu CT) scans, biomechanical testing, and histological analysis. Lrp6(+/-) mice had significantly decreased stiffness and strength at 28 days post fracture (PF) and significantly decreased BV/TV, total density, immature bone density, and mature area within the callus on day-14 and -21 PF; they had significantly increased empty callus area at days 14 and 21 PF. Our results demonstrate that the heterozygous deletion of Lrp6 impairs fracture healing, which suggests that Lrp6 has a role in fracture healing. |
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Address |
[Burgers, Travis A.; Zahatnansky, Juraj; Mason, James J.; Williams, Bart O.] Van Andel Res Inst, Program Skeletal Dis & Tumor Microenvironm, Ctr Canc & Cell Biol, Grand Rapids, MI 49503 USA, Email: bart.williams@vai.org |
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Nature Publishing Group |
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English |
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ISSN |
2095-4700 |
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Notes |
WOS:000383357500001 |
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Call Number |
UAI @ eduardo.moreno @ |
Serial |
654 |
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