Wnt4 signaling mediates protective effects of melatonin on new bone formation in an inflammatory environment
Wnt4 signaling mediates protective effects of melatonin on new bone formation in an inflammatory environment
复制标题
Wnt4信号介导褪黑激素对炎症环境中新骨形成的保护作用
DOI：
10.1096/fj.201900093rr
复制
发表时间：
2019-09-01
期刊：
影响因子：
4.8
通讯作者：
Liu, Hui
中科院分区：
文献类型：
--
作者：
Li, Xiang;Li, Zihao;Liu, Hui
越来越多的证据表明，炎性细胞因子对成骨前体细胞新骨形成的抑制作用是净骨密度降低的关键原因。褪黑激素已被证明是骨质疏松症的潜在治疗候选者。然而，它是否能够拮抗炎性细胞因子对成骨前体细胞的抑制作用迄今尚不清楚。本研究利用人骨髓基质细胞和MC 3 T3-E1前成骨细胞的细胞培养系统，观察到褪黑素在正常和炎症条件下均能诱导成骨，Wnt 4在炎症条件下对褪黑素诱导成骨起重要作用，Wnt 4在褪黑素诱导成骨过程中起重要作用，Wnt 4在褪黑素诱导成骨过程中起重要作用。3）褪黑素和Wnt 4通过激活β-catenin和p38-JNK MAPK通路与一种独特的卷曲LDL受体相关蛋白复合物相互作用而诱导骨形成：4）褪黑素以Wnt 4依赖的方式抑制NF-κ B B对骨形成的抑制作用; 5）褪黑素通过ERK 1/2-Pax 2-Egr 1途径诱导Wnt 4表达。总之，我们发现了一种新的机制，褪黑激素诱导骨形成的炎症环境。褪黑激素诱导的Wnt 4表达是其骨诱导作用和NF-κ B对骨形成的抑制作用所必需的。我们的新发现可能为其潜在的翻译应用提供有用的信息。Li，X.，Li，Z.，王杰，Li，Z.，崔，H.，Dai，G.，Chen，S.，Zhang，M.，郑志，Zhan，Z.，Liu，H. wnt 4信号介导褪黑素对炎症环境中新骨形成的保护作用。
Growing evidence shows that the inhibitory effect of inflammatory cytokines on new bone formation by osteogenic precursor cells is a critical cause of net bone-density reduction. Melatonin has been proven to be a potential therapeutic candidate for osteoporosis. However, whether it is capable of antagonizing the suppressing effect of inflammatory cytokines on osteogenic precursor cells is so far elusive. In this study, using the cell culture system of human bone marrow stromal cells and MC3T3-E1 preosteoblasts, we recorded the following vital observations that provided insights of melatonin-induced bone formation: 1) melatonin induced bone formation in both normal and inflammatory conditions; 2) Wnt4 was essential for melatonin-induced bone formation in inflammatory stimulation; 3) melatonin- and Wnt4-induced bone formation occurred via activation of beta-catenin and p38-JNK MAPK pathways by interaction with a distinct frizzled LDL receptor-related protein complex; 4) melatonin suppressed the inhibitory effect of NF-kappa B on osteogenesis in a Wnt4-dependent manner; and 5) melatonin induced Wnt4 expression through the ERK1/2-Pax2-Egr1 pathway. In summary, we showed a novel mechanism of melatonin-induced bone formation in an inflammatory environment. Melatonin-induced Wnt4 expression is essential for its osteoinductive effect and the inhibitory effect of NF-kappa B on bone formation. Our novel findings may provide useful information for its potential translational application.-Li, X., Li, Z., Wang, J., Li, Z., Cui, H., Dai, G., Chen, S., Zhang, M., Zheng, Z., Zhan, Z., Liu, H. Wnt4 signaling mediates protective effects of melatonin on new bone formation in an inflammatory environment.