title: Staphylococcal enterotoxin C2 expedites bone consolidation in distraction osteogenesis.
abstract: Distraction osteogenesis (DO) technique could be used to manage large-size bone defect successfully, but DO process usually requires long duration of bone consolidation. Innovative approaches for augmenting bone consolidation are of great need. Staphylococcal enterotoxin C2 (SEC2) has been found to suppress osteoclastogenesis of mesenchymal stem cells in vitro. In this study, we investigated the effect of SEC2 on proliferation and osteogenic differentiation of rat bone marrow derived mesenchymal stem cells (rBMSCs). Further, we locally administrated SEC2 (10 ng/ml) or PBS into the distraction gap in Sprague-Dawley male rat DO model every 3 days till termination at 3 and 6 weeks. The regenerates were subjected to X-rays, micro-computed tomography, mechanical testing, histology, and immunohischemistry examinations to assess new bone quality. SEC2 had no effect on cell viability. The calcium deposition was remarkably increased and osteogenic marker genes were significantly up-regulated in rBMSCs treated with SEC2. In rat DO model, SEC2 group had higher bone volume/total tissue volume in the regenerates. At 6 weeks, mechanical properties were significantly higher in SEC2-treated tibiae comparing to the control group. Histological analysis confirmed that the new bone had improved quality in SEC2 treated group, where the osteocalcin and osterix expression in the regenerates was up-regulated, indicating faster bone formation. The current study demonstrated that SEC2 local injection promotes osteogenesis and enhanced bone consolidation in DO. The findings support application of SEC2 as a potential novel strategy to expedite bone consolidation in patients undergoing DO treatment. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1215-1225, 2017.
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.|Department of Orthopaedics and Traumatology, Stem Cells and Regenerative Medicine Laboratory, Room 904, 9/F, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Orthopaedics and Traumatology, Stem Cells and Regenerative Medicine Laboratory, Room 904, 9/F, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, PR China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Orthopaedics and Traumatology, Stem Cells and Regenerative Medicine Laboratory, Room 904, 9/F, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, PR China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Orthopaedics and Traumatology, Stem Cells and Regenerative Medicine Laboratory, Room 904, 9/F, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics and Traumatology, Stem Cells and Regenerative Medicine Laboratory, Room 904, 9/F, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, PR China.|The CUHK-ACC Space Medicine Centre, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, PR China.
authors.forename: Jinfang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics and Traumatology, Stem Cells and Regenerative Medicine Laboratory, Room 904, 9/F, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, PR China.
authors.forename: Wayne Yuk-Wai
authors.initials: WY
authors.lastname: Lee
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, PR China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Chai
authors.affiliation: Department of Orthopaedics and Traumatology, Stem Cells and Regenerative Medicine Laboratory, Room 904, 9/F, Li Ka Shing Institute of Health Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, PR China.|The CUHK-ACC Space Medicine Centre, The Chinese University of Hong Kong Shenzhen Research Institute, Shenzhen, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D055119:Elastic Modulus; D004768:Enterotoxins / Q000494:pharmacology* / Q000627:therapeutic use; D007378:Interleukins / Q000097:blood; D008297:Male; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D010012:Osteogenesis / Q000187:drug effects*; D019857:Osteogenesis, Distraction; D061251:Primary Cell Culture; D017207:Rats, Sprague-Dawley; D055114:X-Ray Microtomography
chemical_list: D004768:Enterotoxins; D007378:Interleukins; C034959:enterotoxin C, staphylococcal
keywords: SEC2; bone consolidation; distraction; osteogenesis