Department of Biological Sciences, University of Ulsan, Ulsan 680-749, Republic of Korea.
Department of Food Science and Nutrition, University of Ulsan, Ulsan 680-749, Republic of Korea.
Bone. 2018 Nov;116:279-289. doi: 10.1016/j.bone.2018.08.014. Epub 2018 Aug 23.
The autophagy pathway has been suggested to influence skeletal structure by modulating bone metabolism. Recent findings suggest that microRNAs (miR) play a critical role in autophagy. We hypothesized that inflammation induces miR-155, which enhances autophagy in osteoclasts (OC), leading to inflammatory bone loss. The expression of miR-155 was elevated in tibiae from LPS-injected mice and in OC stimulated by lipopolysaccharide (LPS) compared with vehicle treatment. Overexpression of miR-155 enhanced autophagy as well as differentiation in OC, whereas inhibition of endogenous miR-155 decreased both. Transforming growth factor β-activated kinase 1-binding protein 2 (TAB2) was identified as a target gene of miR-155 via binding to the 3'-UTR of TAB2, which directly interacts with BECLIN1. BECLIN1 was dissociated from TAB2, which started to associate with TAK1 when autophagy was induced. Our data demonstrate that LPS-induced miR-155 promoted autophagy to increase OC formation via decreased TAB2.
自噬途径被认为通过调节骨代谢来影响骨骼结构。最近的研究结果表明，microRNAs（miR）在自噬中发挥关键作用。我们假设炎症诱导 miR-155，增强破骨细胞（OC）中的自噬，导致炎症性骨丢失。LPS 注射小鼠的胫骨和 LPS 刺激的 OC 中 miR-155 的表达均高于载体处理。miR-155 的过表达增强了 OC 的自噬和分化，而内源性 miR-155 的抑制则降低了两者。转化生长因子-β激活激酶 1 结合蛋白 2（TAB2）被鉴定为 miR-155 的靶基因，通过与 TAB2 的 3'-UTR 结合，直接与 BECLIN1 相互作用。BECLIN1 从 TAB2 上解离出来，当自噬被诱导时，它开始与 TAK1 结合。我们的数据表明，LPS 诱导的 miR-155 通过降低 TAB2 促进自噬，从而增加 OC 的形成。
