Prophylactic supplementation of sinapic acid ameliorates zoledronic acid induced changes in osteoblast survival and differentiation

Abstract

Zoledronic acid (ZA) is clinically used as anti-catabolic agent to treat bone loss exhibits negative role on osteoblast function which is documented by changes in osteoclast cytoskeleton and morphology, and apoptosis. Despite its clinical success, the detrimental effects of ZA need to be addressed to enhance its therapeutic success. Sinapic acid (SA) is a known potent antioxidant with osteogenic properties. Based on this knowledge we investigated the role of SA prophylactic supplementation in ameliorating ZA induced changes in osteoblasts. In a series of experiments we concluded that SA inhibited ZA induced oxidative stress , inhibition of osteoblast differentiation and mineralization . ZA exposure significantly exhibited dose dependent reduction in osteoblast viability, increase in ROS generation and induce apoptosis. However, upon pre-treatment with SA, the effects were antagonized. Furthermore, at molecular level, the expression of osteoblast marker genes Runx2, Col-I and ALP levels were significantly reduced under ZA. Pre-treatment with therapeutic doses of SA prevented these changes and promoted osteoblast differentiation and mineralization by improving calcium deposition. Additionally, SA stimulated mir-590/21-Smad7 signaling to prevent ZA effects in osteoblast. Altogether, our study results emphasized that administration of SA would serve as a beneficial combinatorial therapy in improving the therapeutic effects of ZA and minimizing its undesirable effects on osteoblasts.