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      Systemic administration of sclerostin monoclonal antibody accelerates fracture healing in the femoral osteotomy model of young rats.

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          Abstract

          Genetic studies have demonstrated that sclerostin was a key negative regulator of bone formation. Sclerostin monoclonal antibody (Scl-Ab) treatment enhanced bone healing in experimental fracture healing. The purpose was to investigate the effects of systemic Scl-Ab administration on open fracture healing in young rats. Unilateral femoral fractures were generated in eight-week-old Sprague-Dawley rats. Rats were treated with vehicle or Scl-Ab for 6weeks. Fracture healing was evaluated by western blotting, immunohistochemistry, histology, radiography, micro-CT, and biomechanical testing. In addition, the bone mass of intact femur was also evaluated by micro-CT. The results showed that, at 1 and 2weeks after fracture, proliferating cell nuclear antigen (PCNA) score and bone morphogenetic protein-2 (BMP-2) expression in the Scl-Ab group were significantly increased compared with the control group. A decrease in cartilage in the Scl-Ab group was also observed after fracture, and this was accompanied by more rapider fracture healing. At 4 and 6weeks, there were significant increases in bone mass and mechanical properties in the calluses from Scl-Ab group compared with control group. In addition, Scl-Ab treatment also showed significant anabolic effects in intact femur. In conclusion, systemic Scl-Ab administration has a significant enhancement in a rat femoral osteotomy model. These results support the therapeutic potential of Scl-Ab as a noninvasive strategy to enhance open fracture healing.

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          Author and article information

          Journal
          Int. Immunopharmacol.
          International immunopharmacology
          1878-1705
          1567-5769
          Jan 2015
          : 24
          : 1
          Affiliations
          [1 ] Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Jiaotong University, China.
          [2 ] Department of Orthopedic Surgery, Shanghai Jiao Tong University affiliated Sixth People's Hospital, Shanghai Jiaotong University, China.
          [3 ] Department of Orthopedic Surgery, Shanghai Jiao Tong University affiliated Sixth People's Hospital, Shanghai Jiaotong University, China. Electronic address: lixiaolinwz@sina.cn.
          Article
          S1567-5769(14)00445-7
          10.1016/j.intimp.2014.11.010
          25479724
          f0c9466c-d140-46b4-bc70-70f6270de37d
          Copyright © 2014 Elsevier B.V. All rights reserved.

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