MFG‐E8 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells through GSK3β/β‐catenin signaling pathway

间充质干细胞 碱性磷酸酶 化学 基因敲除 生长分化因子 细胞生物学 鱼腥草素骨 骨钙素 分子生物学 生物 骨形态发生蛋白 生物化学 基因 细胞凋亡
作者
Jinwu Bai,Weijun Zhang,Chenwei Zhou,Guangfeng Zhao,Huiming Zhong,Kai Hang,Jianxiang Xu,Wei Zhang,Erman Chen,Jiaqi Wu,Ling Liu,Deting Xue
出处
期刊:The FASEB Journal [Wiley]
卷期号:37 (6)
标识
DOI:10.1096/fj.202201417rrr
摘要

Fracture nonunion and bone defects are challenging for orthopedic surgeons. Milk fat globule-epidermal growth factor 8 (MFG-E8), a glycoprotein possibly secreted by macrophages in a fracture hematoma, participates in bone development. However, the role of MFG-E8 in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is unclear. We investigated the osteogenic effect of MFG-E8 in vitro and in vivo. The CCK-8 assay was used to assess the effect of recombinant human MFG-E8 (rhMFG-E8) on the viability of hBMSCs. Osteogenesis was investigated using RT-PCR, Western blotting, and immunofluorescence. Alkaline phosphatase (ALP) and Alizarin red staining were used to evaluate ALP activity and mineralization, respectively. An enzyme-linked immunosorbent assay was conducted to evaluate the secretory MFG-E8 concentration. Knockdown and overexpression of MFG-E8 in hBMSCs were established via siRNA and lentivirus vector transfection, respectively. Exogenous rhMFG-E8 was used to verify the in vivo therapeutic effect in a tibia bone defect model based on radiographic analysis and histological evaluation. Endogenous and secretory MFG-E8 levels increased significantly during the early osteogenic differentiation of hBMSCs. Knockdown of MFG-E8 inhibited the osteogenic differentiation of hBMSCs. Overexpression of MFG-E8 and rhMFG-E8 protein increased the expression of osteogenesis-related genes and proteins and enhanced calcium deposition. The active β-catenin to total β-catenin ratio and the p-GSK3β protein level were increased by MFG-E8. The MFG-E8-induced enhanced osteogenic differentiation of hBMSCs was partially attenuated by a GSK3β/β-catenin signaling inhibitor. Recombinant MFG-E8 accelerated bone healing in a rat tibial-defect model. In conclusion, MFG-E8 promotes the osteogenic differentiation of hBMSCs by regulating the GSK3β/β-catenin signaling pathway and so, is a potential therapeutic target.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
大幅提高文件上传限制,最高150M (2024-4-1)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
刚刚
刚刚
1秒前
1秒前
1秒前
cc完成签到,获得积分20
1秒前
健忘芷蕊发布了新的文献求助30
1秒前
Ava应助kayyu采纳,获得10
2秒前
8R60d8应助NN采纳,获得10
2秒前
啦啦啦啦啦完成签到,获得积分10
2秒前
远乐完成签到,获得积分10
2秒前
Ella关注了科研通微信公众号
3秒前
sobereva发布了新的文献求助30
3秒前
福西西关注了科研通微信公众号
3秒前
3秒前
居家家发布了新的文献求助10
4秒前
Smiley完成签到 ,获得积分10
4秒前
lilylucky完成签到,获得积分10
4秒前
阿钉发布了新的文献求助10
4秒前
ZZZ发布了新的文献求助10
5秒前
5秒前
小张发布了新的文献求助10
6秒前
6秒前
7秒前
7秒前
轻松半邪发布了新的文献求助10
8秒前
小贤完成签到,获得积分20
8秒前
8秒前
Akim应助BABY五齿采纳,获得10
9秒前
栗子应助爱听歌的华采纳,获得10
9秒前
10秒前
Ethan完成签到 ,获得积分10
10秒前
XB914发布了新的文献求助10
10秒前
静谧180发布了新的文献求助10
11秒前
12秒前
共享精神应助小张采纳,获得10
13秒前
yyy发布了新的文献求助10
13秒前
Lexa发布了新的文献求助10
13秒前
脑洞疼应助rh1006采纳,获得20
14秒前
高分求助中
The late Devonian Standard Conodont Zonation 2000
The Lali Section: An Excellent Reference Section for Upper - Devonian in South China 1500
Nickel superalloy market size, share, growth, trends, and forecast 2023-2030 1000
Smart but Scattered: The Revolutionary Executive Skills Approach to Helping Kids Reach Their Potential (第二版) 1000
Mantiden: Faszinierende Lauerjäger Faszinierende Lauerjäger 800
PraxisRatgeber: Mantiden: Faszinierende Lauerjäger 800
A new species of Coccus (Homoptera: Coccoidea) from Malawi 500
热门求助领域 (近24小时)
化学 医学 生物 材料科学 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 基因 遗传学 催化作用 物理化学 免疫学 量子力学 细胞生物学
热门帖子
关注 科研通微信公众号,转发送积分 3245545
求助须知:如何正确求助?哪些是违规求助? 2889187
关于积分的说明 8257144
捐赠科研通 2557542
什么是DOI,文献DOI怎么找? 1386164
科研通“疑难数据库(出版商)”最低求助积分说明 650285
邀请新用户注册赠送积分活动 626568