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-κB ligand (RANKL). The forced reduction of Lyn caused a striking increase in the RANKL-induced PLCγ1, Ca2+, and NFATc1 responses during differentiation. These data suggest that Lyn plays a negative role in osteoclastogenesis by interfering with the PLCγ1-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. © 2009 Federation of European Biochemical Societies.
Yoon, S. H., Lee, Y., Kim, H. J., Lee, Z. H., Hyung, S. W., Lee, S. W., & Kim, H. H. (2009). Lyn inhibits osteoclast differentiation by interfering with PLCγ1-mediated Ca2+ signaling. FEBS Letters, 583(7), 1164–1170. https://doi.org/10.1016/j.febslet.2009.03.005