Ampelopsis brevipedunculata extract prevents bone loss by inhibiting osteoclastogenesis in vitro and in vivo.
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.
Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. kimjy1014@gmail.com.
Ju-Young
JY
Kim
Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. beryls@wku.ac.kr.
Sun-Hyang
SH
Park
Bioindustrial Process Research Center, Bio-Materials Research Institute, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, Jeonbuk 580-185, Korea. ohhm@kribb.re.kr.
Hyun Mee
HM
Oh
Korea Institute of Science and Technology for Eastern Medicine (KISTEM), NeuMed Inc., Seoul 130-831, Korea. Ksc960@naver.com.
Sung Chul
SC
Kwak
Department of Anatomy, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. phone8418@hanmail.net.
Jong Min
JM
Baek
Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. ckhlms@wku.ac.kr.
Myeung Su
MS
Lee
Bioindustrial Process Research Center, Bio-Materials Research Institute, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, Jeonbuk 580-185, Korea. rho-m@kribb.re.kr.
Mun Chual
MC
Rho
Imaging Science-based Lung and Bone Diseases Research Center, Wonkwang University, Iksan, Jeonbuk 570-749, Korea. jmoh@wku.ac.kr.
Jaemin
J
Oh
D000135:Acid Phosphatase / Q000378:metabolism; D032421:Ampelopsis / Q000737:chemistry*; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D056657:Cathepsin K / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D039661:Integrin beta3 / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D050778:NFATC Transcription Factors / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry*; D018547:Plant Stems / Q000737:chemistry*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C499636:DC-STAMP protein, mouse; D020672:I-kappa B Proteins; D039661:Integrin beta3; D007527:Isoenzymes; D008565:Membrane Proteins; D050778:NFATC Transcription Factors; D009419:Nerve Tissue Proteins; C494005:Nfatc1 protein, mouse; C527519:OC-STAMP protein, mouse; C450519:Oscar protein, mouse; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D011956:Receptors, Cell Surface; C505689:Tnfsf11 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; C534132:Ctsk protein, mouse