Mechanical stretch increases Smad3-dependent CCN2 expression in inner meniscus cells

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
Takayuki FurumatsuToshifumi Ozaki

Abstract

The intrinsic zone-specific properties of the menisci are determined by biomechanical environments. In this study, we examined mechanical stretch-dependent expression of multifunctional growth factor CYR61/CTGF/NOV (CCN) 2, and investigated the role of CCN2 in meniscus cells. Uni-axial cyclic tensile strain (CTS) was applied using a STB-140 system. CTS-induced expression of CCN2 and α1(I) collagen (COL1A1) was assessed by quantitative real-time PCR analysis. The distribution of CCN2 and Smad2/3 in stretched cells was investigated by immunohistochemical analysis. Smad2/3-dependent CCN2 transactivation was measured by luciferase reporter assay. The relationship between Smad2/3 and CTS-induced CCN2 transcription was investigated by chromatin immunoprecipitation. CTS stimulated gene expression of CCN2 and COL1A1 in inner meniscus cells, but not in outer meniscus cells. Recombinant CCN2 increased COL1A1 expression only in inner meniscus cells. CCN2 synthesis and nuclear translocalization of phosphorylated Smad2/3 in inner meniscus cells were stimulated by CTS. The CCN2 promoter activity was synergistically enhanced by overexpressed Smad3 in stretched inner meniscus cells, but was not by Smad2. Chromatin immunoprecipitation revealed ...Continue Reading

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Citations

Jan 22, 2013·Expert Opinion on Emerging Drugs·Merlin C Thomas
Nov 13, 2012·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Masataka FujiiToshifumi Ozaki
Mar 4, 2015·Journal of Biomechanics·Amy L McNulty, Farshid Guilak
Nov 30, 2016·Connective Tissue Research·Takaaki TanakaToshifumi Ozaki
Sep 11, 2019·The American Journal of Sports Medicine·Shogo HashimotoHirotaka Chikuda
Dec 1, 2012·Current Opinion in Nephrology and Hypertension·Susan V McLennanStephen M Twigg
Apr 12, 2019·Science Translational Medicine·Zheng-Zheng ZhangDong Jiang
Jan 31, 2015·Journal of Biomaterials Applications·Shuhei OdaMasashi Neo
Nov 22, 2018·Journal of Cell Communication and Signaling·Yusuke KamatsukiMasaharu Takigawa
Apr 1, 2020·Journal of Orthopaedic Science : Official Journal of the Japanese Orthopaedic Association·Yuki OkazakiToshifumi Ozaki
Feb 23, 2021·Journal of Tissue Engineering·Alexander Ra SzojkaAdetola B Adesida
Sep 21, 2021·Hip International : the Journal of Clinical and Experimental Research on Hip Pathology and Therapy·Yoshi KawamuraToshifumi Ozaki
Sep 21, 2021·Frontiers in Bioengineering and Biotechnology·Alexander R A SzojkaAdetola B Adesida

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