| First Author | Yang Z | Year | 2017 |
| Journal | J Biol Chem | Volume | 292 |
| Issue | 4 | Pages | 1178-1186 |
| PubMed ID | 27941021 | Mgi Jnum | J:239234 |
| Mgi Id | MGI:5828023 | Doi | 10.1074/jbc.M116.764928 |
| Citation | Yang Z, et al. (2017) Phospholipase Cgamma1 (PLCgamma1) Controls Osteoclast Numbers via Colony-stimulating Factor 1 (CSF-1)-dependent Diacylglycerol/beta-Catenin/CyclinD1 Pathway. J Biol Chem 292(4):1178-1186 |
| abstractText | Phospholipases Cgamma (PLCgamma) 1 and 2 are a class of highly homologous enzymes modulating a variety of cellular pathways through production of inositol 1,4,5-trisphosphate and diacylglycerol (DAG). Our previous studies demonstrated the importance of PLCgamma2 in osteoclast (OC) differentiation by modulating inositol 1,4,5-trisphosphate-mediated calcium oscillations and the up-regulation of the transcription factor NFATc1. Surprisingly, despite being expressed throughout osteoclastogenesis, PLCgamma1 did not compensate for PLCgamma2 deficiency. Because both isoforms are activated during osteoclastogenesis, it is plausible that PLCgamma1 modulates OC development independently of PLCgamma2. Here, we utilized PLCgamma1-specific shRNAs to delete PLCgamma1 in OC precursors derived from wild type (WT) mice. Differently from PLCgamma2, we found that PLCgamma1 shRNA significantly suppresses OC differentiation by limiting colony-stimulating factor 1 (CSF-1)-dependent proliferation and beta-catenin/cyclinD1 levels. Confirming the specificity toward CSF-1 signaling, PLCgamma1 is recruited to the CSF-1 receptor following exposure to the cytokine. To understand how PLCgamma1 controls cell proliferation, we turned to its downstream effector, DAG. By utilizing cells lacking the DAG kinase zeta, which have increased DAG levels, we demonstrate that DAG modulates CSF-1-dependent proliferation and beta-catenin/cyclinD1 levels in OC precursors. Most importantly, the proliferation and osteoclastogenesis defects observed in the absence of PLCgamma1 are normalized in PLCgamma1/DAG kinase zeta double null cells. Taken together, our study shows that PLCgamma1 controls OC numbers via a CSF-1-dependent DAG/beta-catenin/cyclinD1 pathway. |
