| First Author | Sasaki H | Year | 2009 |
| Journal | Free Radic Biol Med | Volume | 47 |
| Issue | 2 | Pages | 189-99 |
| PubMed ID | 19409483 | Mgi Jnum | J:150599 |
| Mgi Id | MGI:3851058 | Doi | 10.1016/j.freeradbiomed.2009.04.025 |
| Citation | Sasaki H, et al. (2009) Receptor activator of nuclear factor-kappaB ligand-induced mouse osteoclast differentiation is associated with switching between NADPH oxidase homologues. Free Radic Biol Med 47(2):189-99 |
| abstractText | Reactive oxygen species (ROS) have been suggested to regulate receptor activator of nuclear factor-kappaB ligand (RANKL)-stimulated osteoclast differentiation. Stimulation of wild-type mouse bone marrow monocyte/macrophage lineage (BMM) cells by RANKL down-regulated NADPH oxidase 2 (Nox2) mRNA expression by half. RANKL reciprocally increased Nox1 mRNA levels and newly induced Nox4 transcript expression. BMM cells from Nox1 knockout (Nox1(-/-)) as well as Nox2(-/-) mice generated ROS in response to RANKL and differentiated into osteoclasts in the same way as wild-type BMM cells, which was assessed by the appearance of tartrate-resistant acid phosphatase-positive, multinucleated cells having the ability to form resorption pits and by the expression of osteoclast marker genes. A small interfering RNA (siRNA) targeting Nox1 or Nox2 failed to inhibit the RANKL-stimulated ROS generation and osteoclast formation in wild-type cells, whereas Nox1 and Nox2 siRNAs significantly suppressed the ROS generation and osteoclast formation in Nox2(-/-) and Nox1(-/-) cells, respectively. We also confirmed that Nox4 siRNA did not affect the RANKL-dependent events in Nox2(-/-) cells, whereas p22(phox) siRNA suppressed the events in both wild-type and Nox1(-/-) cells. Collectively, our results suggest that there may be a flexible compensatory mechanism between Nox1 and Nox2 for RANKL-stimulated ROS generation to facilitate osteoclast differentiation. |
