γ-Tocotrienol induced the proliferation and differentiation of MC3T3-E1 cells through the stimulation of the Wnt/β-catenin signaling pathway

作者：Xu, Weili^*; Li, Yutong; Feng, Rennan; He, Pan; Zhang, Yuqi

来源：Food & Function, 2022, 13(1): 398-410.

DOI：10.1039/d1fo02583j

• BONE HISTOMORPHOMETRIC PARAMETERS
• VITAMIN-E
• BETA-CATENIN
• OSTEOBLASTIC DIFFERENTIATION
• ALPHA-TOCOPHEROL
• MINERAL DENSITY
• CYCLIN D1
• MALE RATS
• EXPRESSION
• OSTEOPOROSIS

gamma-Tocotrienol (gamma-T3), an isoprenoid phytochemical, has shown the promotion of osteoblast proliferation and differentiation in our previous study. In this study, its underlying mechanism was investigated through regulating the Wnt/beta-catenin signaling pathway in MC3T3-E1 cells. Comparative experiment results showed that gamma-T3, not alpha-tocopherol (alpha-TOC) increased more significantly the viability and differentiation in MC3T3-E1 cells. After that, the cells were incubated with 10 mM LiCl, or 4 mu M gamma-T3 with or without 1 mu M XAV-939. gamma-T3 at 4 mu M stimulated the Wnt/beta-catenin signaling pathway by increasing the expression and nuclear accumulation of beta-catenin, and the expressions of their downstream factors, such as cyclin-D1, c-Myc, BMP2 and BMP-4 in MC3T3-E1 cells. gamma-T3 not only upregulated the viability, induced G0/G1 to the S phase, and promoted the expressions of PCNA (Proliferating Cell Nuclear Antigen) and Ki-67, but also increased ALP activity and the expressions of ON, OPN and OCN. Moreover, the effects of gamma-T3 on the MC3T3-E1 cells resembled the actions of LiCl, an activator of the Wnt/beta-catenin signaling pathway. Notably, all these effects of gamma-T3 on the MC3T3-E1 cells were completely blocked by the Wnt/beta-catenin signaling pathway inhibitor XAV-939. Our data demonstrated that gamma-T3 can target beta-catenin to enhance the Wnt/beta-catenin signaling pathway, which led to increased expressions of the downstream cell proliferation and cell cycle-associated (cyclin D1 and c-myc), and cell differentiation-associated (BMP-2 and BMP-4) target genes, and ultimately promoted MC3T3-E1 cell proliferation and differentiation. Therefore, gamma-T3 may be a potential agent to prevent and reverse osteoporosis due to its safety and powerful abilities of osteogenesis.

• 单位
  哈尔滨医科大学