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

• Published in: Inflammation 2018-10, Vol.41 (5), p.1621-1630
• Main Authors: Yanoshita, Makoto, Hirose, Naoto, Okamoto, Yuki, Sumi, Chikako, Takano, Mami, Nishiyama, Sayuri, Asakawa-Tanne, Yuki, Horie, Kayo, Onishi, Azusa, Yamauchi, Yuka, Mitsuyoshi, Tomomi, Kunimatsu, Ryo, Tanimoto, Kotaro
• Format: Article
• Language: English
• Subjects: Animals; Biomedical and Life Sciences; Biomedicine; Cell Line; Chondrocytes; Chondrocytes - metabolism; Cyclooxygenase-2; Cytokines - genetics; Cytokines - metabolism; Extracellular signal-regulated kinase; Focal adhesion kinase; Focal Adhesion Protein-Tyrosine Kinases - metabolism; Focal Adhesion Protein-Tyrosine Kinases - physiology; Gene Expression; IL-1β; Immunology; Inflammation; Inflammation - metabolism; Internal Medicine; MAP kinase; MAP Kinase Signaling System; Mechanical properties; Mechanical stimuli; Mice; Original Article; Pathology; Pharmacology/Toxicology; Phosphorylation; Polymerase chain reaction; Protein-tyrosine kinase receptors; Rheumatology; Signal transduction; Tensile Strength; Tumor necrosis factor-α; Up-Regulation; Western blotting
• ISSN: 0360-3997; 1573-2576
• DOI: 10.1007/s10753-018-0805-8

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.