Abstract
Osteoclasts play a critical role in bone resorbing disorders such as osteoporosis, periodontitis, and rheumatoid arthritis. Therefore, discovery of agents capable of suppressing osteoclast differentiation may aid the development of a therapeutic access for the treatment of pathological bone loss. Ampelopsis brevipedunculata has been used as herbal folk medicine to treat liver diseases and inflammation in Asia. However, its effects on osteoclast differentiation are unknown. We were aimed to investigate the anti-osteoclastogenic activity in vitro and in vivo and to elucidate the underlying mechanism of Ampelopsis brevipedunculata extract (ABE). In this study, ABE inhibited receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation, the formation of filamentous actin rings and the bone resorbing activity of mature osteoclasts. ABE inhibited RANKL-induced p38 and IκB phosphorylation and IκB degradation. Also, ABE suppressed the mRNA and protein expression of nuclear factor of activated T cells c1 (NFATc1) and c-Fos, and the mRNA expression of genes required for cell fusion and bone resorption, such as osteoclast-associated receptor (OSCAR), tartrate resistant acid phosphatase (TRAP), cathepsin K, dendritic cell-specific transmembrane protein (DC-STAMP), β3-integrin and osteoclast stimulatory transmembrane protein (OC-STAMP). Furthermore, results of micro-CT and histologic analysis indicated that ABE remarkably prevented lipopolysaccharide (LPS)-induced bone erosion. These results demonstrate that ABE prevents LPS-induced bone erosion through inhibition of osteoclast differentiation and function, suggesting the promise of ABE as a potential cure for various osteoclast-associated bone diseases.
Highlights
Bone is a very dynamic organ that is maintained by a delicate balance between osteoclast-mediated bone destruction and osteoblast-mediated bone formation
receptor activator of NF-kappa B ligand (RANKL) differentiated the BMMs of the control group into tartrate resistant acid phosphatase (TRAP)-positive mature multinucleated osteoclasts, Ampelopsis brevipedunculata (ABE) decreased the formation of TRAP-positive multinucleated cells in a dose-dependent manner (Figure 1A,B)
To investigate whether suppressed osteoclastogenesis by ABE was due to the potential toxicity of this product, we examined the cytotoxicity of ABE by XTT
Summary
Bone is a very dynamic organ that is maintained by a delicate balance between osteoclast-mediated bone destruction and osteoblast-mediated bone formation This balance can be disturbed by over-activation of osteoclasts, resulting in bone destruction and fragile bones. Several natural products exert inhibitory effects on osteoclast differentiation and function, leading to suppressed bone loss in vivo. Natural products that regulate osteoclast differentiation and identified the extract of Ampelopsis brevipedunculata (ABE) as one such agent. The effects of ABE on RANKL-induced osteoclast differentiation have not been studied. We investigated the effects of ABE on the signaling pathways involved in osteoclast differentiation and activation, as well as the in vivo effect of ABE in a lipopolysaccharide (LPS)-induced bone erosion mice model
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