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Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Sci+Rep 2018 ; 8 (ä): ä Nephropedia Template TP
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Mechanical loading induces primary cilia disassembly in tendon cells via TGF? and HDAC6 #MMPMID30038235
Rowson DT; Shelton JC; Screen HRC; Knight MM
Sci Rep 2018[]; 8 (ä): ä PMID30038235show ga
This study used isolated human tenocytes to test the hypothesis that cyclic mechanical strain directly stimulates primary cilia disassembly, and to elucidate the mechanisms involved. Cells were seeded onto flexible membranes and strained at 0?3%; 1?Hz, for up to 24?hours. Cilia length and prevalence progressively reduced with increasing strain duration but showed full recovery within 2?hours of strain removal. The response to loading was not influenced by actin organisation as seen in other cell types. However, the loading response could be recreated by treatment with TGF?. Furthermore, treatment with the HDAC6 inhibitor Tubacin, or a TGF? receptor inhibitor both prevented strain induced cilia disassembly. These data are the first to describe primary cilia expression in isolated tenocytes, showing that mechanical strain regulates cilia expression independent of changes in tendon extracellular matrix. Furthermore, we show that cilia disassembly is mediated by the activation of TGF? receptors leading to activation of HDAC6. Previous studies have shown that cilia are required for TGF? signalling and that tendon mechanosignalling is mediated by TGF?. The present study therefore suggests a novel feedback mechanism whereby cilia disassembly inhibits prolonged TGF? activation in response to continuous cyclic loading.