Pioglitazone plus (−)‐epigallocatechin gallate: a novel approach to enhance osteogenic performance in aged bone marrow mesenchymal stem cells

Previously, we reported that netoglitazone, a thiadolidinedione, enhanced both adipogenesis and osteoblastogenesis, and that fatty acid synthase knockdown could selectively repress the adipogenic effect. Here, molecular evidence further demonstrated that pioglitazone enhanced osteoblastic differentiation at least through the protein kinase A/glycogen synthase kinase 3β signaling. (-)-Epigallocatechin gallate (EGCG), a fatty acid synthase inhibitor, selectively retained pioglitazone's pro-osteoblastic effect. Cultures of aged human bone marrow mesenchymal stem cells (bmMSCs) in alginate scaffolds revealed that pioglitazone and EGCG cooperatively enhanced osteoblastic differentiation, biological apatite production, and bone-like tissue maturation. These findings demonstrate that the combination of pioglitazone and EGCG is a promising strategy to enhance osteogenic performance in aged bmMSCs for the development of advanced bone graft materials.