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The effect of P2X7R-mediated Ca2+ signaling in OPG-induced osteoclasts adhesive structure damage.

Ma, Yonggang; Zhao, Hongyan; Chile, Chung; Wang, Chao; Zheng, Jiaming; Song, Ruilong; Zou, Hui; Gu, Jianhong; Bian, Jianchun; Liu, Zongping.
Exp Cell Res; : 111555, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31415763
Osteoclast adhesion is important for bone resorption. Osteoprotegerin inhibits osteoclast differentiation and bone resorption via Ca2+ 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 Ca2+-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 integrinαvß3, 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 Ca2+-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 Ca2+-related protein activation. However, P2X7R knockdown aggravated osteoprotegerin-induced osteoclast adhesion damage via Ca2+ signaling. In conclusion, the P2X7R-Ca2+ NFATc1 signaling pathway has a key functional role in osteoprotegerin-induced osteoclast adhesion structure damage.
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