| First Author | Wang Y | Year | 2018 |
| Journal | J Cell Sci | Volume | 131 |
| Issue | 11 | PubMed ID | 29724913 |
| Mgi Jnum | J:263186 | Mgi Id | MGI:6160560 |
| Doi | 10.1242/jcs.213967 | Citation | Wang Y, et al. (2018) IL1beta and TNFalpha promote RANKL-dependent adseverin expression and osteoclastogenesis. J Cell Sci 131(11):jcs213967 |
| abstractText | Adseverin is an actin-binding protein involved in osteoclastogenesis, but its role in inflammation-induced bone loss is not well-defined. Here, we examined whether IL1beta and TNFalpha regulate adseverin expression to control osteoclastogenesis in mouse primary monocytes and RAW264.7 cells. Adseverin was colocalized with subcortical actin filaments and was enriched in the fusopods of fusing cells. In precursor cells, adseverin overexpression boosted the formation of RANKL-induced multinucleated cells. Both IL1beta and TNFalpha enhanced RANKL-dependent TRAcP activity by 1.6-fold and multinucleated cell formation (cells with >/=3 nuclei) by 2.6- and 3.3-fold, respectively. However, IL1beta and TNFalpha did not enhance osteoclast formation in adseverin-knockdown cells. RANKL-dependent adseverin expression in bone marrow cells was increased by both IL1beta (5.4-fold) and TNFalpha (3.3-fold). Luciferase assays demonstrated that this expression involved transcriptional regulation of the adseverin promoter. Activation of the promoter was restricted to a 1118 bp sequence containing an NF-kappaB binding site, upstream of the transcription start site. TNFalpha also promoted RANKL-induced osteoclast precursor cell migration. We conclude that IL1beta and TNFalpha enhance RANKL-dependent expression of adseverin, which contributes to fusion processes in osteoclastogenesis. |
