Enhanced gap junction intercellular communication inhibits catabolic and pro-inflammatory responses in tenocytes against heat stress


Elevation of tendon core temperature during severe activity is well known. However, its effects on tenocyte function have not been studied in detail. The present study tested a hypothesis that heat stimulation upregulates tenocyte catabolism, which can be modulated by the inhibition or the enhancement of gap junction intercellular communication (GJIC). Tenocytes isolated from rabbit Achilles tendons were subjected to heat stimulation at 37 °C, 41 °C or 43 °C for 30 min, and changes in cell viability, gene expressions and GJIC were examined. It was found that GJIC exhibited no changes by the stimulation even at 43 °C, but cell viability was decreased and catabolic and proinflammatory gene expressions were upregulated. Inhibition of GJIC demonstrated further upregulated catabolic and proinflammatory gene expressions. In contrast, enhanced GJIC, resulting from forced upregulation of connexin 43 gene, counteracted the heat-induced upregulation of catabolic and proinflammatory genes. These findings suggest that the temperature rise in tendon core could upregulate catabolic and proinflammatory activities, potentially leading to the onset of tendinopathy, and such upregulations could be suppressed by the enhancement of GJIC. Therefore, to prevent tendon injury at an early stage from becoming chronic injury, tendon core temperature and GJIC could be targets for post-activity treatments.

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Type I collagen alpha 2 chain




Fluorescence loss in photobleaching


Glyceraldehyde 3-phosphate dehydrogenase


Gap junction intercellular communication


Heat shock protein




Matrix metalloproteinase




Transient receptor potential vanilloid-1

18αGA :

18α glycyrrhetinic acid


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EM thanks Professor Takeo Matsumoto in Nagoya University for generous supports. The present study was supported in part by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grants 25702022 and 16 K01346.

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Correspondence to Eijiro Maeda.

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Maeda, E., Kimura, S., Yamada, M. et al. Enhanced gap junction intercellular communication inhibits catabolic and pro-inflammatory responses in tenocytes against heat stress. J. Cell Commun. Signal. 11, 369–380 (2017). https://doi.org/10.1007/s12079-017-0397-3

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  • FLIP
  • Gap junction
  • Heat stimulation
  • Intercellular communication
  • Tendinopathy
  • Tenocytes