Regulation Of Tgf Beta Signalling By Trpv4 In Chondrocytes

The growth factor TGF beta and the mechanosensitive calcium-permeable cation channel TRPV4 are both important for the development and maintenance of many tissues. Although TRPV4 and TGF beta both affect core cellular functions, how their signals are integrated is unknown. Here we show that pharmacological activation of TRPV4 significantly increased the canonical response to TGF beta stimulation in chondrocytes. Critically, this increase was only observed when TRPV4 was activated after, but not before TGF beta stimulation. The increase was prevented by pharmacological TRPV4 inhibition or knockdown and is calcium/CamKII dependent. RNA-seq analysis after TRPV4 activation showed enrichment for the TGF beta signalling pathway and identified JUN and SP1 as key transcription factors involved in this response. TRPV4 modulation of TGF beta signalling represents an important pathway linking mechanical signalling to tissue development and homeostasis.