title: PEP-1-FK506BP12 inhibits matrix metalloproteinase expression in human articular chondrocytes and in a mouse carrageenan-induced arthritis model.
abstract: The 12 kDa FK506-binding protein (FK506BP12), an immunosuppressor, modulates T cell activation via calcineurin inhibition. In this study, we investigated the ability of PEP-1-FK506BP12, consisting of FK506BP12 fused to the protein transduction domain PEP-1 peptide, to suppress catabolic responses in primary human chondrocytes and in a mouse carrageenan-induced paw arthritis model. Western blotting and immunofluorescence analysis showed that PEP-1-FK506BP12 efficiently penetrated chondrocytes and cartilage explants. In interleukin-1β (IL-1β)-treated chondrocytes, PEP-1-FK506BP12 significantly suppressed the expression of catabolic enzymes, including matrix metalloproteinases (MMPs)-1, -3, and -13 in addition to cyclooxygenase-2, at both the mRNA and protein levels, whereas FK506BP12 alone did not. In addition, PEP-1-FK506BP12 decreased IL-1β-induced phosphorylation of the mitogen-activated protein kinase (MAPK) complex (p38, JNK, and ERK) and the inhibitor kappa B alpha. In the mouse model of carrageenan-induced paw arthritis, PEP-1-FK506BP12 suppressed both carrageenan-induced MMP-13 production and paw inflammation. PEP-1-FK506BP12 may have therapeutic potential in the alleviation of OA progression.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang 431-060; Institute for Skeletal Aging, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Hyun Sook
authors.initials: HS
authors.lastname: Hwang
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang 431-060; Institute for Skeletal Aging, Hallym University, Chuncheon 200-702, Korea.
authors.forename: In Young
authors.initials: IY
authors.lastname: Park
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Internal Medicine, Kangnam Sacred Heart Hospital, Seoul 150-950, Korea.
authors.forename: Young Ok
authors.initials: YO
authors.lastname: Jung
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang 431-060; Institute for Skeletal Aging, Hallym University, Chuncheon 200-702, Korea.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Kim
mesh_terms: D000818:Animals; D001168:Arthritis / Q000139:chemically induced / Q000150:complications / Q000201:enzymology* / Q000473:pathology*; D002351:Carrageenan; D002358:Cartilage, Articular / Q000473:pathology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004195:Disease Models, Animal; D004487:Edema / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use; D022061:Tacrolimus Binding Protein 1A / Q000378:metabolism*; D014161:Transduction, Genetic
chemical_list: D053583:Interleukin-1beta; D016328:NF-kappa B; C503924:Pep-1 peptide; D010455:Peptides; D011993:Recombinant Fusion Proteins; D003543:Cysteamine; D002351:Carrageenan; D020928:Mitogen-Activated Protein Kinases; D053509:Matrix Metalloproteinase 13; D022061:Tacrolimus Binding Protein 1A