Ampelopsis brevipedunculata extract prevents bone loss by inhibiting osteoclastogenesis in vitro and in vivo

• Published in: Molecules (Basel, Switzerland) Switzerland), 2014-11, Vol.19 (11), p.18465-18478
• Main Authors: Kim, Ju-Young, Park, Sun-Hyang, Oh, Hyun Mee, Kwak, Sung Chul, Baek, Jong Min, Lee, Myeung Su, Rho, Mun Chual, Oh, Jaemin
• Format: Article
• Language: English
• Subjects: Acid Phosphatase - metabolism; Ampelopsis - chemistry; Ampelopsis brevipedunculata; Ampelopsis brevipedunculata extract (ABE); Animals; Bone diseases; bone loss; bone resorption; Bone Resorption - metabolism; Bone Resorption - pathology; Bone Resorption - prevention & control; Cathepsin K - metabolism; Dendritic cells; Electronic mail systems; Fractures; Humans; I-kappa B Proteins - metabolism; Integrin beta3 - metabolism; Isoenzymes - metabolism; Kinases; Ligands; Male; Medicine; Membrane Proteins - metabolism; Mice; Mice, Inbred ICR; Natural products; Nerve Tissue Proteins - metabolism; NFATC Transcription Factors - metabolism; osteoclast differentiation; Osteoclasts - metabolism; Osteoclasts - pathology; Osteoporosis; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphatase; Phosphorylation - drug effects; Plant Extracts - chemistry; Plant Extracts - pharmacology; Plant Roots - chemistry; Plant Stems - chemistry; Proteins; Proto-Oncogene Proteins c-fos - metabolism; RANK Ligand - metabolism; Receptors, Cell Surface - metabolism; Tartrate-Resistant Acid Phosphatase; Tumor necrosis factor-TNF
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules191118465

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.