Volume 26, Issue 8 pp. 1736-1746
ORIGINAL ARTICLE

FAK inhibition protects condylar cartilage under excessive mechanical stress

Makoto Yanoshita

Makoto Yanoshita

Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima prefecture, Japan

Contribution: Data curation, Formal analysis, ​Investigation, Visualization, Writing - original draft

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Naoto Hirose

Corresponding Author

Naoto Hirose

Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima prefecture, Japan

Correspondence

Naoto Hirose, 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.

Email: [email protected]

Contribution: Conceptualization, Methodology, Project administration, Supervision, Writing - review & editing

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Chikako Sumi

Chikako Sumi

Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima prefecture, Japan

Contribution: ​Investigation

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Mami Takano

Mami Takano

Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima prefecture, Japan

Contribution: ​Investigation

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Sayuri Nishiyama

Sayuri Nishiyama

Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima prefecture, Japan

Contribution: ​Investigation

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Eri Tsuboi

Eri Tsuboi

Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima prefecture, Japan

Contribution: ​Investigation

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Azusa Onishi

Azusa Onishi

Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima prefecture, Japan

Contribution: ​Investigation

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Yuka Yamauchi

Yuka Yamauchi

Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima prefecture, Japan

Contribution: ​Investigation

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Yuki Asakawa

Yuki Asakawa

Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima prefecture, Japan

Contribution: Data curation

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Kunimatsu Ryo

Kunimatsu Ryo

Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima prefecture, Japan

Contribution: Data curation

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Kotaro Tanimoto

Kotaro Tanimoto

Department of Orthodontics and Craniofacial Developmental Biology, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima prefecture, Japan

Contribution: Conceptualization, Project administration, Supervision, Writing - review & editing

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First published: 18 June 2020
Citations: 6

Abstract

Objectives

Excessive mechanical stress is assumed to be a major cause of temporomandibular joint (TMJ) osteoarthritis (OA). +Focal adhesion kinase (FAK) is a cytoplasmic non-receptor tyrosine kinase involved in a variety of signaling pathways. Little has been reported on the function of FAK in TMJ-OA. In the present study, we investigated the effect of FAK inhibition on TMJ cartilage under excessive mechanical loading stress.

Materials and Methods

Articular cartilage explants were harvested from the TMJ of rats and subjected to mechanical loading in the presence of an FAK inhibitor in organ culture. The gene expression of inflammatory cytokines was examined after the application of mechanical loading with or without FAK inhibitor. Paraffin-embedded sections of articular cartilage were stained with hematoxylin and eosin, safranin O and fast Green, toluidine blue, TUNEL staining, and immunohistochemical staining and was performed to investigate the protein expression of IL-1β and MMP-13.

Results

Treatment with FAK inhibitor reduced the gene expression of inflammatory cytokines and inhibited the degradation of articular cartilage, as determined histologically. FAK inhibitor treatment also suppressed the protein expression of IL-1β and MMP-13 in the hypertrophic zone, as determined immunohistologically.

Conclusion

Treatment with FAK inhibitor suppresses inflammation and protects condylar cartilage under excessive mechanical loading.

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