Synergistic action of static stretching and BMP-2 stimulation in the osteoblast differentiation of C2C12 myoblasts |
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| Authors: | In Sook Kim Yun Mi Song Tae Hyung Cho Je Yeon Kim Franz E. Weber Soon Jung Hwang |
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| Affiliation: | 1. Dental Research Institute, Seoul National University, Seoul, 110-768, Republic of Korea;2. Interdisciplinary Program of Bioengineering, Brain Korea 21 2nd Program for Craniomaxillofacial Life Science, Seoul National University, Seoul, 110-768, Republic of Korea;3. Lab for Osteology, Department of Craniomaxillofacial Surgery, University Hospital, Zurich, 8091, Switzerland;4. Department of Maxillofacial Cell and Developmental Biology, Department of Oral and Maxillofacial Surgery, School of Dentistry, Seoul National University, Brain Korea 21 2nd Program for Craniomaxillofacial Life Science, Seoul, 110-768, Republic of Korea;1. Postgraduate, Department of Oral and Maxillofacial Surgery, University of Regensburg, Regensburg, Germany;2. Professor for Oral and Maxillofacial Surgery, Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;3. Consultant Surgeon, Department of Oral and Maxillofacial Surgery, University of Regensburg, Regensburg, Germany;4. Consultant Surgeon, Department of Maxillofacial Surgery, University of Lübeck, Lübeck, Germany;6. Head, Institute of Pathology, HELIOS-Medical Centre, Erfurt, Germany;5. Resident, Department of Oral and Maxillofacial Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany;1. CNRS UMR 5628 (LMGP), MINATEC, 3 parvis Louis Néel, 38016 Grenoble, France;2. Université de Grenoble Alpes, Grenoble Institute of Technology, 3 parvis Louis Néel, 38016 Grenoble, France;3. Institute Albert Bonniot, Grenoble, France;4. Center for Biomedical Engineering, Department of Medicine, Brigham and Women''s Hospital, Harvard Medical School, Cambridge, MA 02139, USA;5. Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA;6. Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115, USA;1. Department of Oral and Maxillofacial Radiology, BK21, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, South Korea;2. Department of Oral and Maxillofacial Surgery, BK21, Dental Research Institute, School of Dentistry, Seoul National University, Seoul, South Korea;3. Department of Biomedical Radiation Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, South Korea;1. Orthognathic Surgery Center, Seoul National University Dental Hospital, Korea;2. Department of Oral and Maxillofacial Surgery, Seoul National University Dental Hospital, School of Dentistry, Dental Research Institute, BK 21 Plus, Seoul National University, Korea;1. Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan;2. Department of Orthopaedic Surgery, Kansai Rosai Hospital, 3-1-69 Inabaso, Amagasaki, Hyogo 660-8511, Japan;1. Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region;2. Stem Cell and Regenerative Medicine Consortium, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam Road, Hong Kong Special Administrative Region |
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| Abstract: | Static stretching is a major type of mechanical stimuli utilized during distraction osteogenesis (DO), a general surgical method for the lengthening of bone. The molecular signals that drive the regenerative process in DO include a variety of cytokines. Among these, bone morphogenic protein (BMP, -2 and -4) has been reported to exhibit strongly enhanced expression following the application of mechanical strain during the distraction phase. We hypothesize that mechanical stretching enhances osteoblast differentiation in DO by means of interaction with BMP-2 induced cytokine stimulation. C2C12 pluripotential myoblasts were exposed to stretching load and the resulting cell proliferation and osteoblast differentiation were then examined. The application of static stretching force resulted in significant cell proliferation at day 3, although with variable intensity according to the magnitude of stretching. A combined treatment of stretching load with BMP-2 stimulation significantly increased alkaline phosphatase (ALP) activity and up-regulated the gene expression of osteogenic markers (ALP, type I collagen, osteopontin, osteocalcin, cbfa1, osterix and dlx5). Results obtained with the combined treatment yielded more activity than just the BMP-2 treatment or stretching alone. These results reveal that specific levels of static stretching force increase cell proliferation and effectively stimulate the osteoblast differentiation of C2C12 cells in conjunction with BMP-2 stimulation, thus indicating a synergistic interaction between mechanical strain and cytokine signaling. |
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