MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1β through the MEK-Erk1/2 and Jak/Stat3 Pathways.
MEK1/2 Inhibitor (GDC0623) Promotes Osteogenic Differentiation of Primary Osteoblasts Inhibited by IL-1β through the MEK-Erk1/2 and Jak/Stat3 Pathways.
复制标题
MEK1/2 抑制剂 (GDC0623) 通过 MEK-Erk1/2 和 Jak/Stat3 途径促进受 IL-1β 抑制的原代成骨细胞的成骨分化
DOI：
10.1155/2021/5720145
复制
发表时间：
2021
影响因子：
2.8
通讯作者：
Xu JG
中科院分区：
文献类型：
--
作者：
Zhang ZQ;Hu XS;Lu YC;Zhang JP;Li WY;Zhang WY;Feng W;Ding DF;Xu JG
探讨GDC 0623对IL-1β诱导的成骨细胞成骨分化的影响及其机制。方法论用20 ng/ml IL-1β和0.1 µM GDC 0623处理成骨细胞。通过细胞计数试剂盒8（CCK 8）、EdU测定和蛋白质印迹法[增殖细胞核抗原（PCNA）和细胞周期蛋白D1]评价细胞增殖水平。将成骨细胞在成骨诱导培养基中培养1-3周，之后通过碱性磷酸酶（ALP）染色、茜素红染色、钙浓度、免疫细胞化学染色、实时定量PCR（RT-qPCR）和免疫荧光染色来评估其分化。使用适当的抗体通过蛋白质印迹法进一步评价成骨相关机制。 与对照组相比，IL-1β通过上调MEK-Erk 1/2和Jak-Stat 3通路的活性，以及升高MMP 13和MMP 9的水平，诱导成骨细胞快速增殖，抑制其成骨分化。然而，GDC 0623治疗阻断MEK-Erk 1/2信号通路可逆转这些作用。 C188-9抑制Jak-Stat 3通路，可下调MMP 9和MMP 13的表达，激活MEK-Erk 1/2通路，抑制成骨分化。
We evaluated the effects and mechanisms of GDC0623 on osteogenic differentiation of osteoblasts induced by IL-1β. Methodology. Osteoblasts were treated with 20 ng/ml IL-1β and 0.1 µM GDC0623. Cell proliferation levels were evaluated by the cell counting kit 8 (CCK8), EdU assay, and western blotting [proliferating cell nuclear antigen (PCNA) and Cyclin D1]. Osteoblasts were cultured in an osteogenic induction medium for 1–3 weeks after which their differentiations were assessed by alkaline phosphatase (ALP) staining, Alizarin Red staining, calcium concentration, immunocytochemistry staining, real-time quantitative PCR (RT-qPCR), and immunofluorescence staining. The osteogenesis-associated mechanisms were further evaluated by western blotting using appropriate antibodies. Relative to the control group, IL-1β induced the rapid proliferation of osteoblasts and suppressed their osteogenic differentiations by upregulating the activities of MEK-Erk1/2 as well as Jak-Stat3 pathways and by elevating MMP13 and MMP9 levels. However, blocking of the MEK-Erk1/2 signaling pathway by GDC0623 treatment reversed these effects. Inhibition of Jak-Stat3 pathway by C188-9 downregulated the expression levels of MMP9 and MMP13, activated MEK-Erk1/2 pathway, and inhibited osteogenic differentiation.
登录
查看更多内容
影响因子：
4.6
作者：
Huang JV;Schooling CM
通讯作者：
Schooling CM
影响因子：
2.7
作者：
Franceschi, Renny T.;Ge, Chunxi;Jiang, Di
通讯作者：
Jiang, Di
影响因子：
1.2
作者：
Gosch, M.;Kammerlander, C.;Neuerburg, C.
通讯作者：
Neuerburg, C.
影响因子：
2.8
作者：
Sun, Guojing;Wang, Zhen;Qian, Hongbo
通讯作者：
Qian, Hongbo
影响因子：
0.7
作者：
Liu, F;Woitge, HW;Kream, BE
通讯作者：
Kream, BE