title: Synergistic action of static stretching and BMP-2 stimulation in the osteoblast differentiation of C2C12 myoblasts.
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.
authors.affiliation: Dental Research Institute, Seoul National University, Seoul 110-768, Republic of Korea.
authors.forename: In Sook
authors.initials: IS
authors.lastname: Kim
authors.forename: Yun Mi
authors.initials: YM
authors.lastname: Song
authors.forename: Tae Hyung
authors.initials: TH
authors.lastname: Cho
authors.forename: Je Yeon
authors.initials: JY
authors.lastname: Kim
authors.forename: Franz E
authors.initials: FE
authors.lastname: Weber
authors.forename: Soon Jung
authors.initials: SJ
authors.lastname: Hwang
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000008:administration & dosage*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D040542:Mechanotransduction, Cellular / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D032446:Myoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D010812:Physical Stimulation / Q000379:methods; D013314:Stress, Mechanical
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2