A novel organosulfur compound, thiacremonone, regulates RANKL-induced osteoclast differentiation

Abstract

The medicinal properties of functionally active organosulfur compounds have received great attention for applications in treating various diseases. Thiacremonone (2,4-dihydroxy-2,5-dimethyl-thiophene-3-one, THIA) is a novel organosulfur compound generated from high-temperature-high-pressure-treated garlic and has been reported to display pharmacological effects against various diseases. However, the role of THIA in bone resorbing cells was not reported. Herein, we have examined the pharmacological properties of THIA on osteoclast differentiation in primary cultured bone marrow macrophages (BMMs). Our results showed that THIA suppressed receptor activator of NF-κB ligand (RANKL)-induced gene expression (c-Fos and NF-ATc1) for osteoclast differentiation under no cytotoxicity condition. In addition, THIA significantly inhibited TRAP positive multinucleated osteoclasts and F-actin ring formation during RANKL-mediated osteoclastogenesis. However, in primary cultured calvarial pre-osteoblasts, THIA did not influence the cytotoxicity and osteoblast differentiation, as assessed from the alkaline phosphatase (ALP) activity and mineralized nodule formation. Our findings have suggested that THIA can be considered as a potential agent for the therapeutics of bone diseases such as osteoporosis, alveolar bone resorption, and osteoarthritis.