Eagle's minimum essential medium (MEM), Dulbecco's phosphate-buffered saline (DPBS), dispase, antibiotic–antimycotic mixture, and trypsin-EDTA were obtained commercially (Invitrogen-Gibco, Grand Island, NY); native porcine type 1 collagen (acid solubilized), 5× Dulbecco's modified Eagle's medium (DMEM), and collagen reconstitution buffer were commercially supplied (Nitta Gelatin, Osaka, Japan); other materials used were fetal bovine serum (FBS; JRH Biosciences, Lenexa, KS); bovine plasminogen as well as collagenase, protease inhibitor cocktail, and MPA (Sigma-Aldrich, St. Louis, MO); and SB203580 (Merck Millipore, Darmstadt, Germany). Recombinant human IL-1β and goat polyclonal antibodies to human TIMP-1 and TIMP-2 were obtained commercially (R&D Systems, Minneapolis, MN); other materials used were mouse monoclonal antibodies to rabbit MMP-1 and MMP-3 (Daiichi Fine Chemicals, Toyama, Japan); antibodies to p38 mitogen-activated protein kinase (MAPK), to phosphorylated p38 MAPK (Thr180, Tyr182), to c-Jun NH2-terminal kinase (JNK), to phosphorylated JNK (Thr183, Tyr185), to extracellular signal-regulated kinase 1 or 2 (ERK1/2), and to phosphorylated ERK1/2 (Thr202, Tyr204) (Cell Signaling, Beverly, MA); an enhanced chemiluminescence (ECL) kit as well as horseradish peroxidase (HRP)–conjugated secondary antibodies (GE Healthcare, Piscataway, NJ); culture plates (24- and 96-well) and 60-mm cell culture dishes (Corning Inc., Corning, NY); Coomassie brilliant blue and gelatin (Bio-Rad, Hercules, CA); a cytotoxicity assay (CytoTox 96Non-Radioactive; Promega, Madison, WI); and a cell proliferation assay based on a colorimetric enzyme-linked immunosorbent assay for bromodeoxyuridine (BrdU; Roche, Basel, Switzerland). All media and reagents used for cell culture were endotoxin minimized.