| First Author | Kim K | Year | 2018 |
| Journal | Bone | Volume | 113 |
| Pages | 17-28 | PubMed ID | 29753717 |
| Mgi Jnum | J:266613 | Mgi Id | MGI:6199830 |
| Doi | 10.1016/j.bone.2018.05.009 | Citation | Kim K, et al. (2018) TRIM38 regulates NF-kappaB activation through TAB2 degradation in osteoclast and osteoblast differentiation. Bone 113:17-28 |
| abstractText | The tripartite motif protein 38 (TRIM38), a member of the TRIM family, is involved in various cellular processes such as cell proliferation, differentiation, apoptosis, and antiviral defense. However, the role of TRIM38 in osteoclast and osteoblast differentiation is not yet known. In this study, we report the involvement of TRIM38 in osteoclast and osteoblast differentiation. Overexpression of TRIM38, in osteoclast precursor cells, attenuated receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclast formation, RANKL-triggered NF-kappaB activation, and expression of osteoclast marker genes, such as NFATc1, osteoclast-associated receptor (OSCAR), and tartrate-resistant acid phosphatase (TRAP); and down-regulation of TRIM38 expression showed the opposite effects. Ectopic expression of TRIM38 in osteoblast precursors induced increased osteoblast differentiation and function. Elevated expression of alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin was also observed due to blockade of NF-kappaB activation. Conversely, knockdown of TRIM38 showed the opposite effects. TRIM38 also induced degradation of lysosome-dependent transforming growth factor beta-activated kinase 1 and MAP3K7-binding protein 2 (TAB2), further blocking NF-kappaB activation. Taken together, our data suggest that TRIM38 plays a critical role in bone remodeling as a negative regulator of NF-kappaB in both osteoclast and osteoblast differentiation. |
