title: Systemic administration of sclerostin monoclonal antibody accelerates fracture healing in the femoral osteotomy model of young rats.
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.
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Jiaotong University, China.
authors.forename: Gao
authors.initials: G
authors.lastname: Feng
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University affiliated Sixth People's Hospital, Shanghai Jiaotong University, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Chang-Qing
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University affiliated Sixth People's Hospital, Shanghai Jiaotong University, China.
authors.forename: Chai
authors.initials: C
authors.lastname: Yi-Min
authors.affiliation: Department of Orthopedic Surgery, Shanghai Jiao Tong University affiliated Sixth People's Hospital, Shanghai Jiaotong University, China. Electronic address: lixiaolinwz@sina.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Xiao-Lin
mesh_terms: D045930:Anabolic Agents / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism; D019485:Bone Morphogenetic Proteins / Q000276:immunology*; D002356:Cartilage / Q000187:drug effects* / Q000473:pathology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000188:drug therapy*; D005269:Femur / Q000187:drug effects / Q000601:surgery; D017102:Fracture Healing / Q000187:drug effects*; D005819:Genetic Markers / Q000276:immunology*; D006801:Humans; D008297:Male; D010027:Osteotomy; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D015854:Up-Regulation
chemical_list: D045930:Anabolic Agents; D000911:Antibodies, Monoclonal; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D018809:Proliferating Cell Nuclear Antigen; C486031:Sost protein, rat
keywords: Fracture healing; Monoclonal antibody; Osteotomy; Sclerostin