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Author (up) Burgers, T.A.; Vivanco, J.F.; Zahatnansky, J.; Moren, A.J.V.; Mason, J.J.; Williams, B.O. pdf  doi
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  Title Mice with a heterozygous Lrp6 deletion have impaired fracture healing Type Journal Article
  Year 2016 Publication Bone Research Abbreviated Journal Bone Res.  
  Volume 4 Issue Pages 9 pp  
  Keywords  
  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.  
  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  
  Corporate Author Thesis  
  Publisher Nature Publishing Group Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 2095-4700 ISBN Medium  
  Area Expedition Conference  
  Notes WOS:000383357500001 Approved no  
  Call Number UAI @ eduardo.moreno @ Serial 654  
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