(−)-Epigallocatechin-3-Gallate (EGCG) Enhances Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells

Abstract

Osteoporosis is the second most-prevalent epidemiologic disease in the aging population worldwide. Cross-sectional and retrospective evidence indicates that tea consumption can mitigate bone loss and reduce risk of osteoporotic fractures. Tea polyphenols enhance osteoblastogenesis and suppress osteoclastogenesis in vitro. Previously, we showed that (−)-epigallocatechin-3-gallate (EGCG), one of the green tea polyphenols, increased osteogenic differentiation of murine bone marrow mesenchymal stem cells (BMSCs) by increasing the mRNA expression of osteogenesis-related genes, alkaline phosphatase activity and, eventually, mineralization. We also found that EGCG could mitigate bone loss and improve bone microarchitecture in ovariectomy-induced osteopenic rats, as well as enhancing bone defect healing partially via bone morphogenetic protein 2 (BMP2). The present study investigated the effects of EGCG in human BMSCs. We found that EGCG, at concentrations of both 1 and 10 µmol/L, can increase mRNA expression of BMP2, Runx2, alkaline phosphatase (ALP), osteonectin and osteocalcin 48 h after treatment. EGCG increased ALP activity both 7 and 14 days after treatment. Furthermore, EGCG can also enhance mineralization two weeks after treatment. EGCG without antioxidants also can enhance mineralization. In conclusion, EGCG can increase mRNA expression of BMP2 and subsequent osteogenic-related genes including Runx2, ALP, osteonectin and osteocalcin. EGCG further increased ALP activity and mineralization. Loss of antioxidant activity can still enhance mineralization of human BMSCs (hBMSCs).

Green Tea Catechin (-)-Epigallocatechin-3-Gallate (EGCG) Facilitates Fracture Healing

“…EGCG, one of the most bioactive catechins derived from green tea, can stimulate bone formation both in vitro and in vivo [17,19,20,31]. The effects of EGCG on the promotion of the fracture healing process, however, remain unclear.…”

“…The healing process of fractured bone is regulated by the differentiation of osteoblasts and BMSCs. In our previous study, we indicated that EGCG can facilitate the osteogenic differentiation of murine and human BMSCs especially at 10 µmol/L [17]. At the same concentration, EGCG can also decrease osteoclastogenesis via the regulation of osteoprotegrin (OPG) and the receptor activator of Nuclear factor-kB (RANK) ligand (RANKL) in pre-osteoclast feeder cells, ST2 [32].…”

“…Enhanced BMP-2 expression is known to play an essential role in the initiation of fracture healing [16]. We found that EGCG enhanced BMP-2 mRNA expression in human bone marrow derived mesenchymal stem cells (BMSCs) [17]. EGCG can facilitate osteogenic differentiation of both murine and human BMSCs and eventually increase mineralization in vitro [17,18].…”

“…We found that EGCG enhanced BMP-2 mRNA expression in human bone marrow derived mesenchymal stem cells (BMSCs) [17]. EGCG can facilitate osteogenic differentiation of both murine and human BMSCs and eventually increase mineralization in vitro [17,18]. We previously reported that intraperitoneal injection of EGCG for 3 months in ovariectomized rats could increase bone volume and microarchitecture at a dosage of 3.4 mg/kg/day, which achieved 10 µmol/L in serum.…”

The potential function ofmiR‐135b‐mediated JAK2/STAT3 signaling pathway during osteoblast differentiation

“…With the staining solution being discarded, cells were then rinsed in deionized water three times and photographed under the inverted microscope. The amount of calcium mineral deposits was determined by dissolving cell-bound alizarin red staining (ARS) in 10% acetic acid and the absorbance at 540 nm was measured by an ELISA reader (Bio-tek) [19][20][21]. ARS intensity relative to the control treatment was calculated after normalization to the total protein content.…”