Bee venom attenuates Porphyromonas gingivalis and RANKL-induced bone resorption with osteoclastogenic differentiation.

Porphyromonas gingivalis (P. gingivalis) is one of the major periodontal pathogens leading to inflammation and alveolar bone resorption. Bone resorption is induced by osteoclasts, which are multinucleated giant cells. Osteoclastic bone resorption is mediated by enhanced receptor activator of nuclear factor-kappa B ligand (RANKL) signaling. Therefore, the down-regulation of RANKL downstream signals is regarded as an effective therapeutic target in the treatment of bone loss-associated disorders. The aim of this study was to evaluate whether purified bee venom (BV) could attenuate P. gingivalis-induced inflammatory periodontitis and RANKL-induced osteoclast differentiation. Inflammatory periodontitis induced by P. gingivalis increased alveolar bone resorption and increased expression of TNF-α and IL-1ß, while BV treatment resulted in decreased bone loss and pro-inflammatory cytokines. Similarly, RANKL-induced multinucleated osteoclast differentiation and osteoclast-specific gene expression, such as nuclear factor of activated T cells 1 (NFATc1), cathepsin K, tartrate-resistant acid phosphatase (TRAP), and integrin αvß3 were significantly suppressed by treatment with BV. We show that BV reduces P. gingivalis-induced inflammatory bone loss-related periodontitis in vivo and RANKL-induced osteoclast differentiation, activation, and function in vitro. These results suggest that BV exerts positive effects on inflammatory periodontitis associated osteoclastogenesis.

Antifibrotic Effect of Smad Decoy Oligodeoxynucleotide in a CCl4-Induced Hepatic Fibrosis Animal Model.

Hepatic fibrosis is the wound-healing process of chronic hepatic disease that leads to the end-stage of hepatocellular carcinoma and demolition of hepatic structures. Epithelial⁻mesenchymal transition (EMT) has been identified to phenotypic conversion of the epithelium to mesenchymal phenotype that occurred during fibrosis. Smad decoy oligodeoxynucleotide (ODN) is a synthetic DNA fragment containing a complementary sequence of Smad transcription factor. Thus, this study evaluated the antifibrotic effects of Smad decoy ODN on carbon tetrachloride (CCl4)-induced hepatic fibrosis in mice. As shown in histological results, CCl4 treatment triggered hepatic fibrosis and increased Smad expression. On the contrary, Smad decoy ODN administration suppressed fibrogenesis and EMT process. The expression of Smad signaling and EMT-associated protein was markedly decreased in Smad decoy ODN-treated mice compared with CCl4-injured mice. In conclusion, these data indicate the practicability of Smad decoy ODN administration for preventing hepatic fibrosis and EMT processes.