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http://dx.doi.org/10.5483/BMBRep.2015.48.7.050

PEP-1-FK506BP12 inhibits matrix metalloproteinase expression in human articular chondrocytes and in a mouse carrageenan-induced arthritis model  

Hwang, Hyun Sook (Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital)
Park, In Young (Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital)
Kim, Dae Won (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University)
Choi, Soo Young (Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University)
Jung, Young Ok (Department of Internal Medicine, Kangnam Sacred Heart Hospital)
Kim, Hyun Ah (Division of Rheumatology, Department of Internal Medicine, Hallym University Sacred Heart Hospital)
Publication Information
BMB Reports / v.48, no.7, 2015 , pp. 407-412 More about this Journal
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. [BMB Reports 2015; 48(7): 407-412]
Keywords
Chondrocyte; FK506-binding protein 12; Metalloproteinase; Osteoarthritis; Protein transduction domain;
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Times Cited By KSCI : 3  (Citation Analysis)
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1 Li J, Jiang K, Qiu X et al (2014) Overexpression of CXCR4 is significantly associated with cisplatin-based chemotherapy resistance and can be a prognostic factor in epithelial ovarian cancer BMB Rep 47, 33-38   DOI   ScienceOn
2 Lee H, Ryu J, Kim KA et al (2004) Transduction of yeast cytosine deaminase mediated by HIV-1 Tat basic domain into tumor cells induces chemosensitivity to 5-fluorocytosine. Exp Mol Med 36, 43-51   DOI   ScienceOn
3 Ozaki D, Sudo K, Asoh S, Yamagata K, Ito H, and Ohta S (2004) Transduction of anti-apoptotic proteins into chondrocytes in cartilage slice culture. Biochem Biophys Res Commun 313, 522-527   DOI   ScienceOn
4 Katsura K, Takahashi K, Asoh S et al (2008) Combination therapy with transductive anti-death FNK protein and FK506 ameliorates brain damage with focal transient ischemia in rat. J Neurochem 106, 258-270   DOI   ScienceOn
5 van den Berg A and Dowdy SF (2011) Protein transduction domain delivery of therapeutic macromolecules. Curr Opin Biotechnol 22, 888-893   DOI   ScienceOn
6 Cameron AM, Steiner JP, Roskams AJ, Ali SM, Ronnett GV, and Snyder SH (1995) Calcineurin associated with the inositol 1,4,5-trisphosphate receptor-FKBP12 complex modulates Ca2+ flux. Cell 83, 463-472   DOI   ScienceOn
7 Morris MC, Depollier J, Mery J, Heitz F, and Divita G (2001) A peptide carrier for the delivery of biologically active proteins into mammalian cells. Nat Biotechnol 19, 1173-1176.   DOI   ScienceOn
8 Gros E, Deshayes S, Morris MC et al (2006) A non-covalent peptide-based strategy for protein and peptide nucleic acid transduction. Biochim Biophys Acta 1758, 384-393   DOI   ScienceOn
9 Kang CB, Hong Y, Dhe-Paganon S, and Yoon HS (2008) FKBP family proteins: immunophilins with versatile biological functions. Neurosignals 16, 318-325   DOI   ScienceOn
10 Qi Y, Ogunbunmi EM, Freund EA, Timerman AP, and Fleischer S (1998) FK-binding protein is associated with the ryanodine receptor of skeletal muscle in vertebrate animals. J Biol Chem 273, 34813-34819   DOI   ScienceOn
11 Kim HA, Kim DW, Park J, and Choi SY (2006) Transduction of Cu, Zn-superoxide dismutase mediated by an HIV-1 Tat protein basic domain into human chondrocytes. Arthritis Res Ther 8, R96   DOI   ScienceOn
12 Schiene-Fischer C and Yu C (2001) Receptor accessory folding helper enzymes: the functional role of peptidyl prolyl cis/trans isomerases. FEBS Lett 495, 1-6   DOI   ScienceOn
13 Kim DW, Lee SH, Ku SK et al (2013) Transduced PEP-1-FK506BP ameliorates corneal injury in Botulinum toxin A-induced dry eye mouse model. BMB Rep 46, 124-129   DOI   ScienceOn
14 Kim SY, Sohn EJ, Kim DW et al (2013) Transduced PEP-1-FK506BP ameliorates atopic dermatitis in NC/Nga mice. J Invest Dermatol 131, 1477-1485   DOI   ScienceOn
15 Yang S, Kim J, Ryu JH et al (2010) Hypoxia-inducible factor- 2alpha is a catabolic regulator of osteoarthritic cartilage destruction. Nat Med 16, 687-693   DOI   ScienceOn
16 Klein D, Ribeiro MM, Mendoza V et al (2004) Delivery of Bcl-XL or its BH4 domain by protein transduction inhibits apoptosis in human islets. Biochem Biophys Res Commun 323, 473-478   DOI   ScienceOn
17 Mengshol JA, Vincenti MP, Coon CI, Barchowsky A, and Brinckerhoff CE (2000) Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor kappaB: differential regulation of collagenase 1 and collagenase 3. Arthritis Rheum 43, 801-811   DOI
18 Goldring SR and Goldring MB (2004) The role of cytokines in cartilage matrix degeneration in osteoarthritis. Clin Orthop Relat Res 427 Suppl, S27-S36   DOI
19 Fujii T, Onohara N, Maruyama Y et al (2005) Galpha12/13-mediated production of reactive oxygen species is critical for angiotensin receptor-induced NFAT activation in cardiac fibroblasts. J Biol Chem 280, 23041-23047   DOI   ScienceOn
20 Kabouridis PS, Hasan M, Newson J, Gilroy DW, and Lawrence T (2002) Inhibition of NF-kappa B activity by a membrane-transducing mutant of I kappa B alpha. J Immunol 169, 2587-2593   DOI
21 Goldring MB (2000) The role of the chondrocyte in osteoarthritis. Arthritis Rheum 43, 1916-1926   DOI
22 Goldring MB and Goldring SR (2007) Osteoarthritis. J Cell Physiol 213, 626-634   DOI   ScienceOn
23 Goldring MB and Berenbaum F (2004) The regulation of chondrocyte function by proinflammatory mediators: prostaglandins and nitric oxide. Clin Orthop Relat Res 427 Suppl, S37-S46   DOI
24 Venkatesan N, Barre L, Benani A et al (2004) Stimulation of proteoglycan synthesis by glucuronosyltransferase-I gene delivery: a strategy to promote cartilage repair. Proc Natl Acad Sci U S A 101, 18087-18092   DOI   ScienceOn
25 Lee NH, Jung YS, Lee HY et al (2014) Mouse neutrophils express functional umami taste receptor T1R1/T1R3. BMB Rep 47, 649-654   DOI   ScienceOn
26 Cameron AM, Steiner JP, Sabatini DM, Kaplin AI, Walensky LD, and Snyder SH (1995) Immunophilin FK506 binding protein associated with inositol 1,4,5-trisphosphate receptor modulates calcium flux. Proc Natl Acad Sci U S A 92, 1784-1788   DOI   ScienceOn