Details

Autor(en) / Beteiligte

• Pozo, Arleth
• Regnier, Marine
• Lizotte, Jérôme
• Martineau, Corine
• Scorza, Tatiana
• Moreau, Robert

Titel

Cyclic adenosine monophosphate-dependent activation of transient receptor potential vanilloid 4 (TRPV4) channels in osteoblast-like MG-63 cells

Ist Teil von

• Cellular signalling, 2020-02, Vol.66, p.109486-109486, Article 109486

Ort / Verlag

England: Elsevier Inc

Erscheinungsjahr

2020

Quelle

MEDLINE

Beschreibungen/Notizen

• Parathyroid hormone (PTH) directly interacts with bone remodeling osteoblasts and osteocytes expressing the G-protein coupled receptor PTH receptor 1 (PTH1R), and its osteoanabolic effects mostly involve the cAMP/PKA signaling cascade. Considering that PTH-dependent calcium entry in rat enterocytes is reproduced by the adenylate cyclase agonist forskolin or by cAMP analogues, possible involvement of calcium as a second messenger in PTH-dependent cAMP signaling was investigated in MG-63 cells. First, Ca2+ influx was confirmed in Fluo3-loaded MG-63 cells treated with a cell-permeable cAMP analog. Second, PTH (1–34) and forskolin promoted calcium influxes that were completely abrogated by the PKA inhibitor H-89. Ca2+ entry was not reproduced when PTH (1–34) was combined with the PKC-activating competitor PTH (3–34). Vanilloid transient potential (TRPV) channel inhibitor Ruthenium Red, but not a voltage-dependent calcium channel (VDCC) inhibitor nifedipine, efficiently stunted Ca2+ entry, and comparable abrogation was reproduced in cells treated with TRPV4-selective inhibitor RN-1734 or transfected with TRPV4-specific siRNA. Interestingly, PTH-driven Ca2+ through TRPV4 significantly inhibited MG63 cell migration through a mechanism requiring extracellular Ca2+. In contrast, the inhibitory effects of forskolin on migration were refractory to TRPV4 silencing or to RN-1734. Altogether, our results indicate that single treatment with PTH (1–34) promotes extracellular calcium entry through TRPV4 channels in MG-63 cells through a cAMP/PKA-dependent mechanism, and that this influx affects cell migration. •PTH inhibits MG63 cell migration through TRPV4-dependent calcium influx.•PTH activates TRPV4 channels through the cAMP/PKA signaling pathway.•Adenylyl cyclase agonist forskolin mimics Calcium influx in response to PTH.•Inhibition of TRPV4 abrogates the inhibitory effect of PTH on migration.