Staphylococcal enterotoxin C2 expedites bone consolidation in distraction osteogenesis

• Published in: Journal of orthopaedic research 2017-06, Vol.35 (6), p.1215-1225
• Main Authors: Xu, Jia, Wu, Tianyi, Sun, Yuxin, Wang, Bin, Zhang, Jinfang, Lee, Wayne Yuk‐Wai, Chai, Yimin, Li, Gang
• Format: Article
• Language: English
• Subjects: Animals; bone consolidation; Bone Marrow Cells - drug effects; Cell Differentiation - drug effects; distraction; Drug Evaluation, Preclinical; Elastic Modulus; Enterotoxins - pharmacology; Enterotoxins - therapeutic use; Interleukins - blood; Male; Mesenchymal Stromal Cells - drug effects; osteogenesis; Osteogenesis - drug effects; Osteogenesis, Distraction; Primary Cell Culture; Rats, Sprague-Dawley; SEC2; X-Ray Microtomography
• ISSN: 0736-0266; 1554-527X
• DOI: 10.1002/jor.23372

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.