机构：[1]Guangzhou Univ Chinese Med, Guangzhou, Peoples R China[2]Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Joint Orthopaed, Guangzhou, Peoples R China[3]Guangzhou Univ Chinese Med, Lingnan Med Res Ctr, Guangzhou, Peoples R China[4]Guangzhou Univ Chinese Med, Shenzhen Hosp Futian, Shenzhen, Guangdong, Peoples R China[5]Fujian Tradit Chinese Med Univ, Quanzhou Orthoped Traumatol Hosp, Dept Joint Orthopaed, Quanzhou, Peoples R China[6]Guangzhou Univ Chinese Med, Affiliated Hosp 3, Dept Joint Orthopaed, Guangzhou, Peoples R China
Background. Core fucosylation catalyzed by FUT8 is essential for TGF-beta binding to TGF-beta receptors. Methods. Indirect TGF-beta 1 binding assay was used to evaluate the ability of TGF-beta 1 to bind to TGFBRs, Alizarin red and alkaline phosphatase staining were used to detect osteogenic differentiation and mineralization ability , western blot and quantitative RT-PCR were used to measure the differential expression of osteogenesis-related proteins and genes. Plasmid-mediated gain-of-function study. The scale of core fucosylation modification was detected by Lectin-blot and LCA laser confocal. Results. Our results showed that compared with vehicle treatment, high-dose (10(-6) and 10(-5) M) dexamethasone significantly inhibited cell proliferation, osteogenic differentiation, and FUT8 mRNA expression while promoting mRNA expression of adipogenesis-related genes in MC3T3-E1 cells, suggesting that downregulation of FUT8 is involved in the inhibitory effect of high-dose dexamethasone on osteogenesis. Overexpression of FUT8 significantly promoted osteogenic differentiation and activated TGF-beta/Smad signaling in MC3T3-E1 rens in the presence of high-dose dexamethasone, suggesting that FUT8 reverses the inhibitory effect of high-dose dexamethasone on osteogenesis. In addition, lectin fluorescent staining and blotting showed that overexpression of FUT8 significantly reversed the inhibitory effects of high-dose dexamethasone on core fucosylation of TGFBR1 and TGFBR2. Furthermore, indirect TGF-beta 1 binding assay showed that overexpression of FUT8 remarkably promoted TGF-beta 1 binding to TGFBRs in MC3T3-E1 cells in the presence of high-dose dexamethasone. Conclusions. Taken together, these results suggest that overexpression of FUT8 facilitates counteracting the inhibitory effect of dexamethasone on TGF-beta signaling and osteogenesis.
基金：
National Natural Science Foundation of China (grant
number 81904226 to Ziqi Li) and the Traditional Chinese Medicine Bureau of Guangdong
Province (grant number 20201098 to Ziqi Li).
第一作者机构：[1]Guangzhou Univ Chinese Med, Guangzhou, Peoples R China[2]Guangzhou Univ Chinese Med, Affiliated Hosp 1, Dept Joint Orthopaed, Guangzhou, Peoples R China[3]Guangzhou Univ Chinese Med, Lingnan Med Res Ctr, Guangzhou, Peoples R China[4]Guangzhou Univ Chinese Med, Shenzhen Hosp Futian, Shenzhen, Guangdong, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Guangzhou Univ Chinese Med, Guangzhou, Peoples R China[6]Guangzhou Univ Chinese Med, Affiliated Hosp 3, Dept Joint Orthopaed, Guangzhou, Peoples R China
推荐引用方式(GB/T 7714)：
Wu Zhiming,Lin Tianye,Kang Pan,et al.Overexpression of fucosyltransferase 8 reverses the inhibitory effect of high-dose dexamethasone on osteogenic response of MC3T3-E1 preosteoblasts[J].PEERJ.2021,9:doi:10.7717/peerj.12380.
APA：
Wu, Zhiming,Lin, Tianye,Kang, Pan,Zhuang, Zhikun,Wang, Haibin...&Li, Ziqi.(2021).Overexpression of fucosyltransferase 8 reverses the inhibitory effect of high-dose dexamethasone on osteogenic response of MC3T3-E1 preosteoblasts.PEERJ,9,
MLA：
Wu, Zhiming,et al."Overexpression of fucosyltransferase 8 reverses the inhibitory effect of high-dose dexamethasone on osteogenic response of MC3T3-E1 preosteoblasts".PEERJ 9.(2021)
