title: Uniaxial cyclic stretch promotes osteogenic differentiation and synthesis of BMP2 in the C3H10T1/2 cells with BMP2 gene variant of rs2273073 (T/G).
abstract: Ossification of the posterior longitudinal ligament of the cervical spine (OPLL) is characterized by the replacement of ligament tissues with ectopic bone formation, and this result is strongly affected by genetic and local factors. Two single nucleotide polymorphisms (SNPs) of rs2273073 (T/G) and rs235768 (A/T) of bone morphogenetic protein 2 (BMP2) gene which are associated with OPLL have been reported in our previous report. In this study, we confirmed the connection in 18 case samples analysis of BMP2 gene in OPLL patients; additionally, it was also shown from the OPLL patients with ligament tissues that enchondral ossification and expression of BMP2 were significantly higher compared with the non-OPLL patients by histological examination, immunohistochemistry and Western blotting analysis. To investigate the underlying mechanism, we studied the effect of SNPs in cell model. The C3H10T1/2 cells with different BMP2 gene variants were constructed and then subjected to uniaxial cyclic stretch (0.5 Hz, 10% stretch). In the presence of mechanical stress, the expression of BMP2 protein in C3H10T1/2 cells transfected by BMP2 (rs2273073 (T/G)) and BMP2 (rs2273073 (T/G), rs235768 (A/T)) were significantly higher than the corresponding static groups (P<0.05). In conclusion, these results suggested that BMP2 gene variant of rs2273073 (T/G) could not only increase cell susceptibility to bone transformation similar to pre-OPLL change, but also increase the sensibility to mechanical stress which might play an important role during the progression of OPLL.
authors.affiliation: Department of Orthopedics, Beijing Tian Tan Hospital, Capital Medical University, Dongcheng District, Beijing, China.
authors.forename: Jia-mou
authors.initials: JM
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Beijing Tian Tan Hospital, Capital Medical University, Dongcheng District, Beijing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: CoreLaboratory for Clinical Medical Research, Beijing Tian Tan Hospital, Capital Medical University, Dongcheng District, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Department of Orthopedics, Beijing Tian Tan Hospital, Capital Medical University, Dongcheng District, Beijing, China.
authors.forename: Bao-ge
authors.initials: BG
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Beijing Tian Tan Hospital, Capital Medical University, Dongcheng District, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Orthopedics, Beijing Tian Tan Hospital, Capital Medical University, Dongcheng District, Beijing, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Engineering Mechanics, Tsinghua University, Haidian District, Beijing, China.
authors.forename: Hu-cheng
authors.initials: HC
authors.lastname: Zhao
authors.affiliation: CoreLaboratory for Clinical Medical Research, Beijing Tian Tan Hospital, Capital Medical University, Dongcheng District, Beijing, China.
authors.forename: Ya-jie
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Beijing Tian Tan Hospital, Capital Medical University, Dongcheng District, Beijing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Song
mesh_terms: D000483:Alleles; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics* / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D053595:Embryonic Stem Cells; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D059630:Mesenchymal Stem Cells; D051379:Mice; D017887:Ossification of Posterior Longitudinal Ligament / Q000235:genetics / Q000378:metabolism; D009999:Ossification, Heterotopic / Q000235:genetics; D010012:Osteogenesis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D013314:Stress, Mechanical; D014162:Transfection
chemical_list: D055396:Bone Morphogenetic Protein 2