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Cyclic Tensile Strain Upregulates Pro-Inflammatory Cytokine Expression Via FAK-MAPK Signaling in Chondrocytes

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Abstract

Excessive mechanical stimulation is considered an important factor in the destruction of chondrocytes. Focal adhesion kinase (FAK) is non-receptor tyrosine kinase related to a number of different signaling proteins. Little is known about the function of FAK in chondrocytes under mechanical stimulation. In the present study, we investigated the function of FAK in mechanical signal transduction and the mechanism through which cyclic tensile strain (CTS) induces expression of inflammation-related factors. Mouse ATDC5 chondrogenic cells were subjected to CTS of 0.5 Hz to 10% cell elongation with an FAK inhibitor. The expression of genes encoding COX-2, IL-1β, and TNF-α was examined using real-time RT-PCR after CTS application with FAK inhibitor. Phosphorylation of p-38, ERK, and JNK was analyzed by Western blotting. Differences in COX-2 expression following pretreatment with FAK, p-38, ERK, and JNK inhibitors were compared by Western blotting. We found that CTS increased the expression of genes encoding COX-2, IL-1β, and TNF-α and activated the phosphorylation of FAK, p-38, ERK, and JNK. Pretreatment with an FAK inhibitor for 2 h reduced the expression of genes encoding COX-2, IL-1β, and TNF-α induced by CTS-associated inflammation and decreased phosphorylation of FAK, p-38, ERK, and JNK. Pretreatment with FAK, p-38, ERK, and JNK inhibitors markedly suppressed COX-2 and IL-1β protein expression. In conclusion, FAK appears to regulate inflammation in chondrocytes under CTS via MAPK pathways.

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Acknowledgments

This research was supported by Grant-in-Aid (No. 26861788) for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan.

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Authors and Affiliations

  1. Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Kasumi 1-2-3 Minami-ku, Hiroshima-shi, Hiroshima prefecture, Japan

    Makoto Yanoshita, Naoto Hirose, Chikako Sumi, Mami Takano, Sayuri Nishiyama, Yuki Asakawa-Tanne, Kayo Horie, Azusa Onishi, Yuka Yamauchi & Kotaro Tanimoto

  2. Department of Orthodontics, Division of Oral Health and Development, Hiroshima University Hospital, Hiroshima, Japan

    Yuki Okamoto, Tomomi Mitsuyoshi & Ryo Kunimatsu

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  1. Makoto Yanoshita
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Correspondence to Naoto Hirose.

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Supplementary Figure

Expression of differentiation markers in culture model of chondrogenesis. Induction of mouse embryonal carcinoma-derived cell line ATDC5 differentiation into chondrocyte by insulin and ascorbate treatment. Expression of chondrogenic differentiation marker genes, Type II collagen and Type X collagen were evaluated by real-time RT-PCR. Relative mRNA levels were calculated as the ratio to that of S29. The data presented are the means ± S.D. of the three independent experiments. *p < 0.05, **p < 0.01 compared with day 0. (PPTX 47 kb)

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Yanoshita, M., Hirose, N., Okamoto, Y. et al. Cyclic Tensile Strain Upregulates Pro-Inflammatory Cytokine Expression Via FAK-MAPK Signaling in Chondrocytes. Inflammation 41, 1621–1630 (2018). https://doi.org/10.1007/s10753-018-0805-8

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