IF: 1.90
Original Article

Time-dependent effects of sclerostin antibody on a mouse fracture healing model
L. Cui1*, H. Cheng2*, C. Song3, C. Li4, W.S. Simonet4, H.Z. Ke4, G. Li3,5
1.
Guangdong Key Laboratory for R&D of Natural Drug, Guangdong Medical College, Zhanjiang 524023, Guangdong, PR China
2.
Department of Pathology, State Key Laboratory of Cancer Biology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi’an, Shaanxi 710032, P.R. China
3.
Stem Cell and Regeneration Program, Li Ka Shing Institute of Health Sciences, School of Biomedical Sciences and The Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, SAR China
4.
Metabolic Disorders, Amgen Inc., One Amgen Center Dr., Thousand Oaks, California, 91320 USA
5.
The Chinese University of Hong Kong Shenzhen Research Institute, Nanshan District, Shenzhen, PR China
*
These authors contributed equally and served as co-first author
Abstract
Objectives: Treatment with Sclerostin antibody (Scl-Ab) has shown to enhance fracture healing in rodent and non-human primate models. The current study investigated the time-dependent changes during Scl-Ab treatment in a mouse osteotomy model. Methods: 1 day after osteotomy, C57BL mice received subcutaneous injection with vehicle or Scl-Ab at 25 mg/kg, twice/week for 2, 4, or 6 weeks. 20 mice from each group were necropsied at weeks 2, 4, and 6 for Micro-CT, histomorphometry and mechanical testing examinations. Results: The bone mineral apposition rate at fracture callus was significantly higher in the Scl-Ab treated groups at all the time points. Micro-CT analysis showed that the volumetric bone mineral density (vBMD) and bone volume over tissue volume (BV/TV) in the Scl-Ab treated groups at 4 and 6 weeks were significantly greater than that of vehicle control groups. Mechanical testing showed that the maximum load of failure at the fracture callus increased significantly by 68% at 6 weeks in the Scl-Ab treated groups. Conclusions: This study confirmed that mice treated with Scl-Ab increased bone formation from 2 weeks, bone density and bone volume at 4 weeks, followed by significant increase in bone strength at the fracture site at 6 weeks. These results suggest that applying sclerostin antibody at early stage fracture healing promotes fracture healing.
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