Role of (-)-epigallocatechin-3-gallate in the osteogenic differentiation of human bone marrow mesenchymal stem cells: An enhancer or an inducer?

Epidemiological investigations have revealed that the consumption of green tea, which is a rich source of (-)-epigallocatechin-3-gallate (EGCG), is associated with a reduced risk of osteoporosis. A number of in vitro and in vivo studies have also demonstrated that EGCG exerts a significant positive effect on osteogenesis; however, the single effect of EGCG on osteogenic differentiation has been seldom studied. EGCG was hypothesized to function as an enhancer or an inducer. In the present study, the effect of EGCG on the osteogenic differentiation of primary human bone marrow mesenchymal stem cells (hBMSCs), without other additives, was investigated. Three groups of stem cells were analyzed, which included a negative control group (hBMSCs cultured with culture medium only), an experimental group (cells treated with culture medium containing 2.5, 5 and 10 µM EGCG), and a positive control group (cells cultured with osteogenesis-induced culture medium). After 3, 7, 14 and 21 days, cell proliferation, alkaline phosphatase (ALP) activity and the expression of associated osteogenic genes were analyzed. The results revealed that ALP activity and the expression of associated osteogenic genes, with the exception of bone morphogenetic protein 2 (BMP2), were not affected by EGCG treatment alone. These results indicated that EGCG itself had little effect on the osteogenic differentiation of MSCs; however, EGCG was able to enhance osteogenesis in the presence of osteoinductive agents through the upregulation of BMP2 expression. Additionally, EGCG was shown to promote cell growth, demonstrating its safety as a therapeutic agent. Therefore, the present study indicated that treatment with EGCG was dependent on other osteogenic inducers.