| First Author | Ma Y | Year | 2019 |
| Journal | Exp Cell Res | Volume | 383 |
| Issue | 2 | Pages | 111555 |
| PubMed ID | 31415763 | Mgi Jnum | J:282169 |
| Mgi Id | MGI:6380387 | Doi | 10.1016/j.yexcr.2019.111555 |
| Citation | Ma Y, et al. (2019) The effect of P2X7R-mediated Ca(2+) signaling in OPG-induced osteoclasts adhesive structure damage. Exp Cell Res 383(2):111555 |
| abstractText | Osteoclast adhesion is important for bone resorption. Osteoprotegerin inhibits osteoclast differentiation and bone resorption via Ca(2+) signaling. Purinergic receptor P2X7 (P2X7R) affects osteoclastogenesis by activating transcription factor nuclear factor of activated T cells 1 (NFATc1). However, the detailed mechanism of osteoprotegerin-mediated P2X7R modulation of osteoclast adhesion is unclear. This study aimed to determine the effect of P2X7R on osteoprotegerin-induced damage to osteoclast adhesion. Osteoprotegerin reduced the expression of P2X7R, and protein tyrosine kinase 2 (PYK2) and SRC phosphorylation, and reduced calcium concentration, significantly decreasing Ca(2+)-NFATc1 signaling. 1,2-Bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (acetoxymethyl ester) (BAPTA-AM)/N-(6-Aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride (W-7) partly or absolutely recovered osteoprotegerin-induced osteoclasts adhesion structure damage, including increased the PYK2 and SRC phosphorylation, changed the distribution of PYK2/SRC and integrinalphavbeta3, and inhibited retraction of lamellipodia and filopodia and recovered osteoclast bone resorption activity. In addition, BAPTA-AM/W-7 also increased osteoprotegerin-induced activation of Ca(2+)-NFATc1 signaling, and restored normal P2X7R levels. P2X7R knockdown significantly inhibited osteoclast differentiation, and the formation of lamellipodia and filopodia, reduced the PYK2 and SRC phosphorylation, and inhibited Ca(2+)-related protein activation. However, P2X7R knockdown aggravated osteoprotegerin-induced osteoclast adhesion damage via Ca(2+) signaling. In conclusion, the P2X7R-Ca(2+) NFATc1 signaling pathway has a key functional role in osteoprotegerin-induced osteoclast adhesion structure damage. |
