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Aprotinin, cisplatin (cis-diamminedichloroplatinum(II)), p-coumaric acid, ethanol, N, N-dimethylformamide (DMF), luminol, orthovanadate, and phenylmethylsulfonyl fluoride (PMSF) were obtained from Sigma-Aldrich (Taufkirchen, Germany). Dulbecco’s modified Eagle’s medium (DMEM) with 4 mM L-glutamine and 4.5 mg/ml glucose was obtained from Lonza (Cologne, Germany). Fetal calf serum (FCS) and phosphate-buffered saline (PBS) were purchased from PAN Biotech (Aidenbach, Germany). Leupeptin was purchased from Biomol (Hamburg, Germany). Dimethyl sulfoxide (DMSO), ethylenediaminetetraacetic acid (EDTA), glycerol, hydrogen peroxide (H₂O₂), sodium chloride (NaCl), Tris hydrochloride (Tris-HCl), and Tris ultrapure were purchased from AppliChem (Darmstadt, Germany). PD98059 was purchased from Tocris Bioscience (Wiesbaden-Nordenstadt, Germany), and penicillin-streptomycin was bought from Invitrogen (Darmstadt, Germany). 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) was obtained from Ferak (Berlin, Germany), and SB203580 was purchased from Enzo Life Sciences (Lörrach, Germany). Triton^® X-100 was bought from Roth (Karlsruhe, Germany).

NS-398 was purchased from Alexis Deutschland GmbH (Grünberg, Germany). Aprotinin, Δ-glycerophosphate, ethylenediaminetetraacetic acid (EDTA), leupeptin, lovastatin lactone, luminal, mevastatin, p-coumaric acid, phenylmethylsulfonyl fluoride (PMSF), (R)-mevalonic acid lithium salt, sodium molybdate and sodium orthovanadate were obtained from Sigma-Aldrich (Taufkirchen, Germany). 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) was from Ferak (Berlin, Germany). Dimethyl sulfoxide (DMSO), dithiothreitol (DTT), glycerol, p-nitrophenylphosphate, sodium chloride, sodium dodecylsulfate (SDS) and sodium fluoride were from AppliChem (Darmstadt, Germany) and GW9662 and Nonidet^® P-40 from Enzo Life Sciences (Lörrach, Germany). Lovastatin hydroxy acid, sodium salt, was provided from Toronto Research Chemical (Toronto, Canada) and Triton^® X-100, acetonitrile (LC-MS grade) and trifluoroacetic acid (analytical grade) from Roth (Karlsruhe, Germany). Penicillin-streptomycin was from Invitrogen (Darmstadt, Germany). Dulbecco's Modified Eagle's medium (DMEM) with 4 mM L-glutamine and 4.5 g/L glucose was from Lonza (Cologne, Germany). Phosphate-buffered saline (PBS) and fetal calf serum (FCS) were obtained from PAN Biotech (Aidenbach, Germany).

Samples of articular cartilage were collected from 12 OA patients (age 75.3 ± 13.3 years, six males and six females) who underwent orthopaedic surgery. Articular cartilage was sliced into small pieces and subjected to enzymatic digestion with 0.25% trypsin (Gibco, Thermo Fisher Scientific, Madrid, Spain) for 10 min and with 2 mg/mL type IV collagenase (Sigma-Aldrich Química S.A.) overnight at 37 °C. A 100 µm-pore filter was employed to filter the resulting cells, which were afterwards centrifuged at 430× g for 10 min, resuspended in Dulbecco’s modified Eagle’s medium (DMEM) with 4.5 g/L glucose (25 mM) (Lonza, Madrid, Spain), 10% foetal bovine serum (FBS, Gibco), and 1% penicillin/streptomycin (P/S, Gibco), and plated in adherent culture dishes (Costar Corning Incorporated, New York, NY, USA). Only freshly isolated chondrocytes or chondrocytes between the first- and the second-passages were used for the experiments. For silencing expression experiments, the human chondrocyte cell line TC28a2, widely used in in vitro models for studying molecular pathways involved in physiological and pathological processes in the cartilage [35 (link)], was employed.