title: Mechanical stretch enhances COL2A1 expression on chromatin by inducing SOX9 nuclear translocalization in inner meniscus cells.
abstract: The meniscus plays an important role in controlling the biomechanics of the knee. However, the mechanical stress-related response in meniscus cells remains unclear. We investigated mechanical stretch-regulated gene expression in human meniscus cells. Human inner and outer meniscus cells were prepared from the inner and outer halves of the lateral meniscus. The gene expressions of Sry-type HMG box (SOX) 9 and α1(II) collagen (COL2A1) were assessed by real-time PCR analyses after cyclic tensile strain (CTS) treatment (0.5 Hz, 5% stretch). The localization and phosphorylation of SOX9 were evaluated by immunohistochemical and Western blot (WB) analyses. Chromatin immunoprecipitation (IP) analysis was performed to assess the stretch-related protein-DNA complex formation between SOX9 and the COL2A1 enhancer on chromatin. Type II collagen deposition and SOX9 production were detected only in inner menisci. CTS treatments increased expression of the COL2A1 and SOX9 genes in inner meniscus cells, but not in outer meniscus cells. In addition, CTS treatments stimulated nuclear translocalization and phosphorylation of SOX9 in inner meniscus cells. Chromatin IP analyses revealed that CTS increased the association between SOX9 and its DNA-binding site, included in the COL2A1 enhancer, on chromatin. Our results indicate that inner and outer meniscus cells have different properties in mechanical stretch-induced COL2A1 expression. In inner meniscus cells, mechanical stretch may have an essential role in the epigenetic regulation of COL2A1 expression.
authors.affiliation: Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kanazawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Furumatsu
authors.forename: Motomi
authors.initials: M
authors.lastname: Hachioji
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Oohashi
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Ninomiya
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Ozaki
mesh_terms: D000368:Aged; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008592:Menisci, Tibial / Q000166:cytology / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000378:metabolism*; D013314:Stress, Mechanical
chemical_list: C499177:COL2A1 protein, human; D002843:Chromatin; D024043:Collagen Type II; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human