Effects of Cinnamoyloxy-mammeisin from Geopropolis on Osteoclast Differentiation and Porphyromonas gingivalis-Induced Periodontitis

Author(s)

da Cunha, Marcos Guilherme ; Ramos-Junior, Erivan Schnaider ; Franchin, Marcelo ; Taira, Thaise Mayumi ; Beutler, John A. ; Nobre Franco, Gilson Cesar ; Ikegaki, Masaharu ; de Alencar, Severino Matias ; Fukada, Sandra Yasuyo ; Rosalen, Pedro Luiz

• Document type: Journal article
• Source: Journal of Natural Products; v. 80, n. 6, p. 1893-1899, JUN 2017.
• Web of Science Citations: 7

Abstract

Bone-loss-related diseases such as rheumatoid arthritis, osteomyelitis, osteoporosis, and periodontitis are associated with high rates of morbidity worldwide. These disorders are characterized by an imbalance between the formation and activity of osteoblasts and osteoclasts, leading to bone loss. In this context, we evaluated the effect of cinnamoyloxy-mammeisin (CNM), an anti-inflammatory coumarin found in Melipona scutellaris geopropolis, on key targets related to bone remodeling. In the present study we investigated the in vitro effects of CNM on osteoclast differentiation and M-CSF+RANKL-induced osteoclastogenic marker expression. Additionally, the interference of CNM treatment on osteoclast activity was evaluated by zymography and resorption area. Finally, we assessed the capacity of the compound to mitigate alveolar bone loss in vivo in experimental murine periodontitis induced by Porphyromonas gingivalis. We observed that treatment with CNM impaired osteoclast differentiation, as evidenced by a reduced number of tartrate-resistant acid-phosphatase-positive multinucleated cells (TRAP+) as well as the expression of osteoclastogenic markers upon M-CSF+RANKL-induced stimulation. Similarly, we observed reduced gelatinolytic and resorption capacity in M-CSF+RANKL-induced cells in vitro. Lastly, CNM attenuated alveolar bone loss in an experimental murine periodontitis model. These findings indicate that CNM may be considered a promising treatment for bone loss diseases. (AU)

• FAPESP's process: 12/22002-2 - Chemical elucidation of biocompounds and molecular targets of geopropolis on cancer cell lines
• Grantee: Marcos Guilherme da Cunha
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 11/23635-6 - Isolation and pharmacological evaluation of bioactive molecules from hexane fraction of M. scutellaris geopropolis
• Grantee: Marcos Guilherme da Cunha
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 14/11958-3 - The role of NOD1 and NOD2 in autophagic mechanisms of macrophages and osteoclasts infected with Porphyromonas gingivalis
• Grantee: Erivan Schnaider Ramos Junior
• Support Opportunities: Scholarships in Brazil - Post-Doctoral