title: PEP-1-SIRT2-induced matrix metalloproteinase-1 and -13 modulates type II collagen expression via ERK signaling in rabbit articular chondrocytes.
abstract: Matrix metalloproteinases (MMPs) are critical for the degradation of the extracellular matrix (ECM), which includes cartilage-specific collagen types I, II and XI. We previously found that PEP-1-sirtuin (SIRT)2 could induce dedifferentiation of articular chondrocytes; however, the underlying mechanisms remains unclear. We addressed this in the present study by examining the association between PEP-1-SIRT2 and the expression of MMP-1 and MMP-13 and type II collagen in rabbit articular chondrocytes. We found that PEP-1-SIRT2 increased MMP-1 and -13 expression in a dose- and time-dependent manner, as determined by western blotting. A similar trend in MMP-1 and -13 levels was observed in cultures during expansion to four passages. Pharmacological inhibition of MMP-1 and -13 blocked the PEP-1-SIRT2-induced decrease in type II collagen level. Phosphorylation of extracellular regulated kinase (ERK) was increased by PEP-1-SIRT2; however, treatment with the mitogen-activated protein kinase inhibitor PD98059 suppressed PEP-1-SIRT2-induced MMP-1 and -13 expression and dedifferentiation while restoring type II collagen expression in passage 2 cells. These results suggest that PEP-1-SIRT2 promotes MMP-induced dedifferentiation via ERK signaling in articular chondrocytes.
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Kongju National University, 56 Gongjudaehak-ro, Gongju, Chungnam 32588, Republic of Korea. Electronic address: eoseonghee@kongju.ac.kr.
authors.forename: Seong-Hui
authors.initials: SH
authors.lastname: Eo
authors.affiliation: Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon, Republic of Korea. Electronic address: sychoi@hallym.ac.kr.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
authors.affiliation: Department of Biological Sciences, College of Natural Sciences, Kongju National University, 56 Gongjudaehak-ro, Gongju, Chungnam 32588, Republic of Korea. Electronic address: ksj85@kongju.ac.kr.
authors.forename: Song Ja
authors.initials: SJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology*; D054337:Cell Dedifferentiation / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism*; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism*; D008954:Models, Biological; D010455:Peptides / Q000494:pharmacology*; D011817:Rabbits; D056565:Sirtuin 2 / Q000494:pharmacology*
chemical_list: D024043:Collagen Type II; C503924:Pep-1 peptide; D010455:Peptides; D003543:Cysteamine; D053509:Matrix Metalloproteinase 13; D020781:Matrix Metalloproteinase 1; D056565:Sirtuin 2
keywords: Chondrocytes; ERK signaling; Matrix Metalloproteinases; PEP-1-SIRT2; Type II collagen