Tetrahydroxystilbene Glucoside Regulates Proliferation, Differentiation, and OPG/RANKL/M-CSF Expression in MC3T3-E1 Cells via the PI3K/Akt Pathway

Abstract

Tetrahydroxystilbene glucoside (TSG) is a unique component of the bone-reinforcing herb Radix Polygoni Multiflori Preparata (RPMP). It has the ability to promote bone formation and protect osteoblasts. However, the underlying mechanism remains unclear. To better understand its biological function, we determined TSG’s effect on murine pre-osteoblastic MC3T3-E1 cells by the MTT assay, flow cytometry, FQ-PCR, Western blot, and ELISA. The results showed that TSG caused an elevation of the MC3T3-E1 cell number, the number of cells in the S phase, and the mRNA levels of the runt-related transcription factor-2 (Runx2), osterix (Osx), and collagen type I α1 (Col1a1). In addition, the osteoprotegerin (OPG) mRNA level was up-regulated, while the nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) mRNA levels were down-regulated by TSG. Furthermore, TSG activated the phosphoinosmde-3-kinase/protein kinase B (also known as PI3K/Akt) pathway, and blocking this pathway by the inhibitor LY-294002 could impair TSG’s functions in relation to the MC3T3-E1 cells. In conclusion, TSG could activate the PI3K/Akt pathway and thus promote MC3T3-E1 cell proliferation and differentiation, and influence OPG/RANKL/M-CSF expression. TSG merits further investigation as a potential therapeutic agent for osteoporosis treatment.

Hierarchical Micro-Nano Topography Promotes Cell Adhesion and Osteogenic Differentiation via Integrin α2-PI3K-AKT Signaling Axis

“…Our outcomes showed that PI3K-AKT signaling pathway was activated on SLM-AHT surface, combing with high expression of integrin α2. Since PI3K-AKT signaling had been proved involved in multiple cell functions including cell proliferation, apoptosis, growth, glucose metabolism, migration and differentiation (Gu et al, 2013;Choi et al, 2014;Xu et al, 2015;Fan et al, 2018), we supposed that there might be crosstalk between integrin α2 and PI3K-AKT signaling pathway, and hierarchical micro-nano topography by itself could affect this integrin α2-PI3K-AKT signaling axis. However, whether integrin α2 could activate PI3K-AKT signaling pathway was still unknown.…”

The Antiosteoporosis Effects of Yishen Bugu Ye Based on Its Regulation on the Differentiation of Osteoblast and Osteoclast

“…Recently, traditional Chinese medicines (TCMs) have been attracting increasing attention from researchers because of their pharmacological activities, including antiosteoporotic effects, and exhibition of fewer adverse effects. OP is thought to be mainly caused by kidney deficiency [11]; thus, kidney-tonifying TCM is expected to effectively treat OP. Yishen Bugu Ye (YSBGY) is a TCM composed of 12 types of medicinal herbs, namely, Rhizoma Drynariae, Radix Polygoni Multiflori, Poria, Radix Dipsaci, Radix Paeoniae Alba, Radix Angelica sinensis, Radix Codonopsis, Radix Rehmanniae Preparata, Rhizoma Polygonati, Fructus Lycii, Pyritum, and Pericarpium Citri Reticulatae, and has long been used in China for protecting the kidneys and improving tendon and bone strength.…”

“…It has been shown to increase callus formation and osseointegration, enhance bone strength at the femoral diaphysis in osteoporotic fractures, and restore the femur trabecular bone mineral density (BMD) in female Sprague-Dawley osteoporotic fracture model rats [13]. In addition, Radix Polygoni Multiflori has been shown to promote the proliferation and differentiation of MC3T3-E1 cells by increasing the mRNA concentrations of runt-related transcription factor-2 (Runx2), osterix (Osx), and osteopontin (OPN) and reducing those of RANKL [11]. Radix Rehmanniae Preparata has been reported to improve the microstructure of trabecular bone in rats with dexamethasone-(Dex-) induced OP [14].…”

miRNA-26a-5p Accelerates Healing via Downregulation of PTEN in Fracture Patients with Traumatic Brain Injury

“…PI3K/AKT signaling is a cell-growth-regulatory pathway involved in many diseases 52, 53. Previous studies54, 55 suggested that this pathway is essential for the differentiation of bone progenitor cells. Fan et al 54 .…”