Resveratrol protects against Rankl-induced mineralized bone damage in a transgenic medaka fish model of osteoporosis

Natural substances with bone protective potential always greatly attract researchers for the development of safer and more effective drugs for osteopenia and osteoporosis. Resveratrol (RES), a plant polyphenol found in red grapes and berries has been commonly suggested as supplement for bone health. It has shown bone anabolic and anti-resorptive effects in different in vitro cell cultures and in vivo rodent models. Recently, the medaka fish (Oryzias latipes) has emerged as a valuable model organism for bone research. In this study, we present, for the first time, evidence that resveratrol, tested at five doses (25, 50, 100, 150, and 200 μM), mitigated bone loss induced by Rankl in a transgenic medaka model for osteoporosis. Notably, the dose of 150 μM exhibited the highest bone-protective and anti-resorptive effect, reducing bone loss by approximately 20%. However, at the same dose, RES did not significantly affect the signal densities of green fluorescent protein (GFP) and alizarin complexone (ALC), which represent osteoblasts and mineralized matrix, respectively, in col10a1:nlGFP transgenic medaka larvae. In these larvae, osteoblasts were marked by GFP, and bone was stained with ALC. Our findings provide significant evidence from a non-rodent model regarding the therapeutic potential of resveratrol.