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

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.

3-(4-Methoxyl)-1-(2-(4-coumarin)prop)-2-en-1-one inhibits the differentiation of osteoclasts

“…MCPEO can inhibit the differentiation of BM-MNCs into TRAP positive cells (osteoclasts). The results were consistent with the inhibitory effects of other coumarin derivatives on osteoclast differentiation [17,19].…”

“…Psoralen is a coumarin derivative that is extracted from Chinese herbal medicine, promotes the differentiation of osteoblasts in mouse skull by activating BMP signaling pathways, increases the expression level of osteoblast-specific genes, and enhances the activity of alkaline phosphatase [12]. Coumarin compounds, such as aesculin [15], wedelolactone [16], osthole [17,18], and cinnamoyloxy-mammeisin [19], can inhibit the differentiation and activation of osteoclasts and potentially treat osteoporosis.…”

Modulating calcium‐mediated NFATc1 and mitogen‐activated protein kinase deactivation underlies the inhibitory effects of kavain on osteoclastogenesis and bone resorption

“…Osteoclasts can resorb bone and cartilage, thereby regulating bone remodeling and mineral homeostasis. However, in some bone-loss diseases, such as osteoporosis, rheumatoid arthritis, or periodontitis, a significant increase in either osteoclastogenesis or osteoclast function is found (da Cunha et al, 2017;Miyauchi et al, 2013;Williams, Dharmapatni, & Crotti, 2017). Thus, reducing osteoclast viability is a classic antiresorptive therapeutic strategy for patients suffering from these osteolytic diseases.…”

Chitooligosaccharide inhibits RANKL‐induced osteoclastogenesis and ligation‐induced periodontitis by suppressing MAPK/ c‐fos/NFATC1 signaling

“…Periodontitis characterized by the loss of alveolar bone is the most common oral disease with a prevalence of 10–15% (Xu et al, ). Excessively activated osteoclasts are considered as an important promoting factor in the destruction of alveolar bone in periodontitis (da Cunha et al, ). In our study, we found that CS exhibited obvious protective effects against ABL compared to the ligature group.…”