Mechanical stretch enhances COL2A1 expression on chromatin by inducing SOX9 nuclear translocalization in inner meniscus cells.

Tomoko Kanazawa, Takayuki Furumatsu, Motomi Hachioji, Toshitaka Oohashi, Yoshifumi Ninomiya, Toshihumi Ozaki

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)468-474
Number of pages7
JournalJournal of Orthopaedic Research
Volume30
Issue number3
Publication statusPublished - Mar 2012
Externally publishedYes

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Chromatin
Chromatin Immunoprecipitation
Fourier Analysis
Phosphorylation
Meniscus
Tibial Meniscus
Gene Expression
Mechanical Stress
Collagen Type II
DNA
Biomechanical Phenomena
Epigenomics
Real-Time Polymerase Chain Reaction
Knee
Collagen
Western Blotting
Binding Sites
Genes

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Mechanical stretch enhances COL2A1 expression on chromatin by inducing SOX9 nuclear translocalization in inner meniscus cells. / Kanazawa, Tomoko; Furumatsu, Takayuki; Hachioji, Motomi; Oohashi, Toshitaka; Ninomiya, Yoshifumi; Ozaki, Toshihumi.

In: Journal of Orthopaedic Research, Vol. 30, No. 3, 03.2012, p. 468-474.

Research output: Contribution to journalArticle

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