title: Melittin has a chondroprotective effect by inhibiting MMP-1 and MMP-8 expressions via blocking NF-κB and AP-1 signaling pathway in chondrocytes.
abstract: Bee venom is a natural ingredient produced by the honey bee (Apis mellifera), and has been widely used in China, Korea and Japan as a traditional medicine for various diseases such as arthritis, rheumatism, and skin diseases However, the regulation of the underlying molecular mechanisms of the anti-arthritis by bee venom and its major peptides is largely unknown. In this study, we investigated the potential molecular mechanisms underlying the anti-arthritis effect of bee venom and its major peptides, melittin and apamin, in tumor necrosis factor-α (TNF-α) responsive C57BL/6 mice chondrocyte cells. The bee venom and melittin significantly and selectively suppressed the TNF-α-mediated decrease of type II collagen expression, whereas the apamin had no effects on the type II collagen expression. We, furthermore, found that the bee venom and melittin inhibited the protein expression of matrix metalloproteinase (MMP)-1 and MMP-8, which suggests that the chondroprotective effect of bee venom may be caused by melittin. The inhibitory effects of melittin on the TNF-α-induced MMP-1 and MMP-8 protein expression were regulated by the inhibition of NF-kB and AP-1. In addition, melittin suppressed the TNF-α-induced phosphorylation of Akt, JNK and ERK1/2, but did not affect the phosphorylation of p38 kinase. These results suggest that melittin suppresses TNF-α-stimulated decrease of type II collagen expression by the inhibiting MMP-1 and MMP-8 through regulation of the NF-kB and AP-1 pathway and provision of a novel role for melittin in anti-arthritis action.
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Yun-Jeong
authors.initials: YJ
authors.lastname: Jeong
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea; School of Life Sciences, KNU Creative BioResearch Group (BK21 plus program), Kyungpook National University, Daegu 702-701 Republic of Korea.
authors.forename: Jae-Moon
authors.initials: JM
authors.lastname: Shin
authors.affiliation: School of Life Sciences, KNU Creative BioResearch Group (BK21 plus program), Kyungpook National University, Daegu 702-701 Republic of Korea.
authors.forename: Young-Seuk
authors.initials: YS
authors.lastname: Bae
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Hyun-Ji
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Kwan-Kyu
authors.initials: KK
authors.lastname: Park
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea.
authors.forename: Jung-Yoon
authors.initials: JY
authors.lastname: Choe
authors.affiliation: Department of Agricultural Biology, National Institute of Agricultural Science and Technology, Suwon, Kyunggi-Do 441-100, Republic of Korea.
authors.forename: Sang-Mi
authors.initials: SM
authors.lastname: Han
authors.affiliation: School of Food Science and Technology, Chung-Ang University, Ansung 456-756, Republic of Korea.
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
authors.affiliation: Personalized Tumor Engineering Research Center, Department of Urology, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614-052, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon, Kyunggi-Do 440-746, Republic of Korea.
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 701-947, Republic of Korea.
authors.forename: Hyeun-Wook
authors.initials: HW
authors.lastname: Chang
authors.affiliation: Research Institute of Biomedical Engineering and Department of Medicine, Catholic University of Daegu School of Medicine, Daegu 705-718, Republic of Korea. Electronic address: ycchang@cu.ac.kr.
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
mesh_terms: D000818:Animals; D001514:Bee Venoms / Q000494:pharmacology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D020784:Matrix Metalloproteinase 8 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001514:Bee Venoms; D024042:Collagen Type I; D024043:Collagen Type II; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D020928:Mitogen-Activated Protein Kinases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse; C576328:MMP8 protein, mouse; D020784:Matrix Metalloproteinase 8
keywords: Bee venom; Chondrocyte; Melittin; Type II collagen