Lyn inhibits osteoclast differentiation by interfering with PLCγ1-mediated Ca2+ signaling

Osteoclasts differentiate from macrophage-lineage cells to become specialized for bone resorption function. By a proteomics approach, we found that Lyn was down-regulated by the osteoclast differentiation factor, receptor activator of NF-kappa B ligand (RANKL). The forced reduction of Lyn caused a striking increase in the RANKL-induced PLC gamma 1, Ca2+, and NFATc1 responses during differentiation. These data suggest that Lyn plays a negative role in osteoclastogenesis by interfering with the PLC gamma 1-mediated Ca2+ signaling that leads to NFATc1 activation. Consistent with the in vitro results, in vivo injection of Lyn specific siRNA into mice calvariae provoked a fulminant bone resorption. Our study provides the first evidence of the involvement of Lyn in the negative regulation of osteoclastogenesis by RANKL. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.