Phorbaketal A stimulates osteoblast differentiation through TAZ mediated Runx2 activation

► Phorbaketal A stimulates osteogenesis. ► Phorbaketal A increases TAZ-mediated osteoblast marker gene expression. ► ERK is an important kinase for phorbaketal A induced osteogenic differentiation. ► Phorbaketal A is suggested as a potential compound for stimulating bone formation. Osteoporosis arises from an imbalance between osteoblastic bone formation and osteoclastic bone resorption. In this study, we screened molecules from marine natural products that stimulate osteoblast differentiation. We found that phorbaketal A significantly stimulates osteoblast differentiation in mesenchymal cells. Increased interaction of TAZ and Runx2 stimulated phorbaketal A-induced expression of osteoblastic marker genes. The activation of ERK was important for the stimulation of differentiation because an inhibitor of ERK blocked phorbaketal A-induced osteogenic differentiation. Taken together, the results showed that phorbaketal A stimulates TAZ-mediated osteoblast differentiation through the activation of ERK. TAZphysically interacts with RUNX2 by pull down (View interaction)