Chondrocyte Isolation and Transcriptomic/Proteomic Analysis

We isolated chondrocytes from each cartilage sample as described^{113 (link)} and detailed in full in Supplementary Methods (see Supplementary Information). Assays and analyses were performed as described in Supplementary Methods (see Supplementary Information), and RNA sequencing was performed on the Illumina HiSeq2000 or Hiseq4000 (75 bp paired-ends), with quality control including FastQC 0.11.5 (http://www.bioinformatics.babraham.ac.uk/projects/fastqc). For raw RNA sequencing data details see Data Availability Statement. For protein extracts, we carried out digestion, 6-plex or 10-plex tandem mass tag labeling and peptide fractionation. For samples from 12 knee osteoarthritis patients, we applied a liquid chromatography mass spectrometry (LC-MS) analysis using the Dionex Ultimate 3000 ultra-high-performance liquid chromatography (UHPLC) system coupled with the high-resolution LTQ Orbitrap Velos mass spectrometer (Thermo Fisher Scientific GmbH, Dreieich, Germany). For all remaining samples, LC-MS analysis was performed on the Dionex Ultimate 3000 UHPLC system coupled with the Orbitrap Fusion Tribrid Mass Spectrometer (Thermo Fisher Scientific). For proteomics data details see Data Availability Statement.