[1] A.D. Woolf, B. Pfleger, Burden of major musculoskeletal conditions, Bull World Health Organ 81(9) (2003) 646-56.
[2] C.H. Chou, C.C. Wu, I.W. Song, H.P. Chuang, L.S. Lu, J.H. Chang, S.Y. Kuo, C.H. Lee, J.Y. Wu, Y.T. Chen, V.B. Kraus, M.T. Lee, Genome-wide expression profiles of subchondral bone in osteoarthritis, Arthritis Res Ther 15(6) (2013) R190.
[3] J.N. Katz, Lumbar disc disorders and low-back pain: socioeconomic factors and consequences, J Bone Joint Surg Am 88 Suppl 2 (2006) 21-4.
[4] C. Shepherd, A.E. Reese, L.N. Reynard, J. Loughlin, Expression analysis of the osteoarthritis genetic susceptibility mapping to the matrix Gla protein gene MGP, Arthritis Res Ther 21(1) (2019) 149.
[5] S. Glyn-Jones, A.J. Palmer, R. Agricola, A.J. Price, T.L. Vincent, H. Weinans, A.J. Carr, Osteoarthritis, Lancet 386(9991) (2015) 376-87.
[6] J.W. Bijlsma, F. Berenbaum, F.P. Lafeber, Osteoarthritis: an update with relevance for clinical practice, Lancet 377(9783) (2011) 2115-26.
[7] O. Malaise, D. de Seny, Therapeutic advances in arthritis diseases, Biochem Pharmacol 165 (2019) 1-3.
[8] G. Chen, T. Shi, L. Shi, Characterizing and annotating the genome using RNA-seq data, Sci China Life Sci 60(2) (2017) 116-125.
[9] U. Nagalakshmi, K. Waern, M. Snyder, RNA-Seq: a method for comprehensive transcriptome analysis, Curr Protoc Mol Biol Chapter 4 (2010) Unit 4 11 1-13.
[10] A. Mortazavi, B.A. Williams, K. McCue, L. Schaeffer, B. Wold, Mapping and quantifying mammalian transcriptomes by RNA-Seq, Nat Methods 5(7) (2008) 621-8.
[11] A.A. Pitsillides, F. Beier, Cartilage biology in osteoarthritis--lessons from developmental biology, Nat Rev Rheumatol 7(11) (2011) 654-63.
[12] Y.K. Xu, Y. Ke, B. Wang, J.H. Lin, The role of MCP-1-CCR2 ligand-receptor axis in chondrocyte degradation and disease progress in knee osteoarthritis, Biol Res 48 (2015) 64.
[13] D. Heinegard, T. Saxne, The role of the cartilage matrix in osteoarthritis, Nat Rev Rheumatol 7(1) (2011) 50-6.
[14] A.P. Jaswal, A. Bandyopadhyay, Re-examining osteoarthritis therapy from a developmental biologist's perspective, Biochem Pharmacol 165 (2019) 17-23.
[15] Y. Henrotin, C. Lambert, P. Richette, Importance of synovitis in osteoarthritis: evidence for the use of glycosaminoglycans against synovial inflammation, Semin Arthritis Rheum 43(5) (2014) 579-87.
[16] F. Rannou, S. Poiraudeau, Non-pharmacological approaches for the treatment of osteoarthritis, Best Pract Res Clin Rheumatol 24(1) (2010) 93-106.
[17] W. Zhang, R.W. Moskowitz, G. Nuki, S. Abramson, R.D. Altman, N. Arden, S. Bierma-Zeinstra, K.D. Brandt, P. Croft, M. Doherty, M. Dougados, M. Hochberg, D.J. Hunter, K. Kwoh, L.S. Lohmander, P. Tugwell, OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines, Osteoarthritis Cartilage 16(2) (2008) 137-62.
[18] B.S. Carvalho, R.A. Irizarry, A framework for oligonucleotide microarray preprocessing, Bioinformatics 26(19) (2010) 2363-7.
[19] L. Gautier, L. Cope, B.M. Bolstad, R.A. Irizarry, affy--analysis of Affymetrix GeneChip data at the probe level, Bioinformatics 20(3) (2004) 307-15.
[20] R.A. Irizarry, B. Hobbs, F. Collin, Y.D. Beazer-Barclay, K.J. Antonellis, U. Scherf, T.P. Speed, Exploration, normalization, and summaries of high density oligonucleotide array probe level data, Biostatistics 4(2) (2003) 249-64.
[21] J.T. Leek, W.E. Johnson, H.S. Parker, A.E. Jaffe, J.D. Storey, The sva package for removing batch effects and other unwanted variation in high-throughput experiments, Bioinformatics 28(6) (2012) 882-3.
[22] M.E. Ritchie, B. Phipson, D. Wu, Y. Hu, C.W. Law, W. Shi, G.K. Smyth, limma powers differential expression analyses for RNA-sequencing and microarray studies, Nucleic Acids Res 43(7) (2015) e47.
[23] M.I. Love, W. Huber, S. Anders, Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2, Genome Biol 15(12) (2014) 550.
[24] B. Wang, M. Wang, W. Zhang, T. Xiao, C.H. Chen, A. Wu, F. Wu, N. Traugh, X. Wang, Z. Li, S. Mei, Y. Cui, S. Shi, J.J. Lipp, M. Hinterndorfer, J. Zuber, M. Brown, W. Li, X.S. Liu, Integrative analysis of pooled CRISPR genetic screens using MAGeCKFlute, Nat Protoc 14(3) (2019) 756-780.
[25] D. Szklarczyk, A.L. Gable, D. Lyon, A. Junge, S. Wyder, J. Huerta-Cepas, M. Simonovic, N.T. Doncheva, J.H. Morris, P. Bork, L.J. Jensen, C.V. Mering, STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets, Nucleic Acids Res 47(D1) (2019) D607-D613.
[26] P. Shannon, A. Markiel, O. Ozier, N.S. Baliga, J.T. Wang, D. Ramage, N. Amin, B. Schwikowski, T. Ideker, Cytoscape: a software environment for integrated models of biomolecular interaction networks, Genome Res 13(11) (2003) 2498-504.
[27] C.H. Chin, S.H. Chen, H.H. Wu, C.W. Ho, M.T. Ko, C.Y. Lin, cytoHubba: identifying hub objects and sub-networks from complex interactome, BMC Syst Biol 8 Suppl 4 (2014) S11.
[28] R. Zheng, C. Wan, S. Mei, Q. Qin, Q. Wu, H. Sun, C.H. Chen, M. Brown, X. Zhang, C.A. Meyer, X.S. Liu, Cistrome Data Browser: expanded datasets and new tools for gene regulatory analysis, Nucleic Acids Res 47(D1) (2019) D729-D735.
[29] M. Laavola, T. Leppanen, M. Hamalainen, K. Vuolteenaho, T. Moilanen, R. Nieminen, E. Moilanen, IL-6 in Osteoarthritis: Effects of Pine Stilbenoids, Molecules 24(1) (2018).
[30] E.R. Bastow, K. Last, S. Golub, J.L. Stow, A.C. Stanley, A.J. Fosang, Evidence for lysosomal exocytosis and release of aggrecan-degrading hydrolases from hypertrophic chondrocytes, in vitro and in vivo, Biol Open 1(4) (2012) 318-28.
[31] T. Gui, B.S. He, Q. Gan, C. Yang, Enhanced SOCS3 in osteoarthiritis may limit both proliferation and inflammation, Biotech Histochem 92(2) (2017) 107-114.
[32] A. Gao, T.E. Van Dyke, Role of suppressors of cytokine signaling 3 in bone inflammatory responses, Front Immunol 4 (2014) 506.
[33] M. Enomoto, P.S. Leboy, A.S. Menko, D. Boettiger, Beta 1 integrins mediate chondrocyte interaction with type I collagen, type II collagen, and fibronectin, Exp Cell Res 205(2) (1993) 276-85.
[34] A. Raducanu, E.B. Hunziker, I. Drosse, A. Aszodi, Beta1 integrin deficiency results in multiple abnormalities of the knee joint, J Biol Chem 284(35) (2009) 23780-92.
[35] T. Bengtsson, A. Aszodi, C. Nicolae, E.B. Hunziker, E. Lundgren-Akerlund, R. Fassler, Loss of alpha10beta1 integrin expression leads to moderate dysfunction of growth plate chondrocytes, J Cell Sci 118(Pt 5) (2005) 929-36.
[36] C. Lian, X. Wang, X. Qiu, Z. Wu, B. Gao, L. Liu, G. Liang, H. Zhou, X. Yang, Y. Peng, A. Liang, C. Xu, D. Huang, P. Su, Collagen type II suppresses articular chondrocyte hypertrophy and osteoarthritis progression by promoting integrin beta1-SMAD1 interaction, Bone Res 7 (2019) 8.
[37] N. Ferrara, H.P. Gerber, J. LeCouter, The biology of VEGF and its receptors, Nat Med 9(6) (2003) 669-76.
[38] J.L. Hamilton, M. Nagao, B.R. Levine, D. Chen, B.R. Olsen, H.J. Im, Targeting VEGF and Its Receptors for the Treatment of Osteoarthritis and Associated Pain, J Bone Miner Res 31(5) (2016) 911-24.
[39] S. Kihara, S. Hayashi, S. Hashimoto, N. Kanzaki, K. Takayama, T. Matsumoto, N. Chinzei, K. Iwasa, M. Haneda, K. Takeuchi, K. Nishida, R. Kuroda, Cyclin-Dependent Kinase Inhibitor-1-Deficient Mice are Susceptible to Osteoarthritis Associated with Enhanced Inflammation, J Bone Miner Res 32(5) (2017) 991-1001.
[40] R.J. Stefanetti, S. Voisin, A. Russell, S. Lamon, Recent advances in understanding the role of FOXO3, F1000Res 7 (2018).
[41] M. Ekoff, T. Kaufmann, M. Engstrom, N. Motoyama, A. Villunger, J.I. Jonsson, A. Strasser, G. Nilsson, The BH3-only protein Puma plays an essential role in cytokine deprivation induced apoptosis of mast cells, Blood 110(9) (2007) 3209-17.
[42] Y. Akasaki, A. Hasegawa, M. Saito, H. Asahara, Y. Iwamoto, M.K. Lotz, Dysregulated FOXO transcription factors in articular cartilage in aging and osteoarthritis, Osteoarthritis Cartilage 22(1) (2014) 162-70.
[43] F. Lang, N. Strutz-Seebohm, G. Seebohm, U.E. Lang, Significance of SGK1 in the regulation of neuronal function, J Physiol 588(Pt 18) (2010) 3349-54.
[44] W. Huang, C. Cheng, W.S. Shan, Z.F. Ding, F.E. Liu, W. Lu, W. He, J.G. Xu, Z.S. Yin, Knockdown of SGK1 alleviates the IL-1beta-induced chondrocyte anabolic and catabolic imbalance by activating FoxO1-mediated autophagy in human chondrocytes, FEBS J 287(1) (2020) 94-107.
[45] Z. Wang, S. Ni, H. Zhang, Y. Fan, L. Xia, N. Li, Silencing SGK1 alleviates osteoarthritis through epigenetic regulation of CREB1 and ABCA1 expression, Life Sci (2020) 118733.
[46] Q. Tang, Y. Chen, C. Meyer, T. Geistlinger, M. Lupien, Q. Wang, T. Liu, Y. Zhang, M. Brown, X.S. Liu, A comprehensive view of nuclear receptor cancer cistromes, Cancer Res 71(22) (2011) 6940-7.
[47] J. Shen, S. Li, D. Chen, TGF-beta signaling and the development of osteoarthritis, Bone Res 2 (2014).
[48] B.A. Hocevar, T.L. Brown, P.H. Howe, TGF-beta induces fibronectin synthesis through a c-Jun N-terminal kinase-dependent, Smad4-independent pathway, EMBO J 18(5) (1999) 1345-56.
[49] S. Pushpakom, F. Iorio, P.A. Eyers, K.J. Escott, S. Hopper, A. Wells, A. Doig, T. Guilliams, J. Latimer, C. McNamee, A. Norris, P. Sanseau, D. Cavalla, M. Pirmohamed, Drug repurposing: progress, challenges and recommendations, Nat Rev Drug Discov 18(1) (2019) 41-58.
[50] J. Lamb, E.D. Crawford, D. Peck, J.W. Modell, I.C. Blat, M.J. Wrobel, J. Lerner, J.P. Brunet, A. Subramanian, K.N. Ross, M. Reich, H. Hieronymus, G. Wei, S.A. Armstrong, S.J. Haggarty, P.A. Clemons, R. Wei, S.A. Carr, E.S. Lander, T.R. Golub, The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease, Science 313(5795) (2006) 1929-35.
[51] E.R. LaVallie, P.S. Chockalingam, L.A. Collins-Racie, B.A. Freeman, C.C. Keohan, M. Leitges, A.J. Dorner, E.A. Morris, M.K. Majumdar, M. Arai, Protein kinase Czeta is up-regulated in osteoarthritic cartilage and is required for activation of NF-kappaB by tumor necrosis factor and interleukin-1 in articular chondrocytes, J Biol Chem 281(34) (2006) 24124-37.
[52] L. Pujols, L. Fernandez-Bertolin, M. Fuentes-Prado, I. Alobid, J. Roca-Ferrer, N. Agell, J. Mullol, C. Picado, Proteasome inhibition reduces proliferation, collagen expression, and inflammatory cytokine production in nasal mucosa and polyp fibroblasts, J Pharmacol Exp Ther 343(1) (2012) 184-97.
[53] H. Frase, J. Hudak, I. Lee, Identification of the proteasome inhibitor MG262 as a potent ATP-dependent inhibitor of the Salmonella enterica serovar Typhimurium Lon protease, Biochemistry 45(27) (2006) 8264-74.
[54] A.F. Kisselev, W.A. van der Linden, H.S. Overkleeft, Proteasome inhibitors: an expanding army attacking a unique target, Chem Biol 19(1) (2012) 99-115.
[55] I.R. Garrett, D. Chen, G. Gutierrez, M. Zhao, A. Escobedo, G. Rossini, S.E. Harris, W. Gallwitz, K.B. Kim, S. Hu, C.M. Crews, G.R. Mundy, Selective inhibitors of the osteoblast proteasome stimulate bone formation in vivo and in vitro, J Clin Invest 111(11) (2003) 1771-82.
[56] G. Koren, S.J. Soldin, Cardiac glycosides, Clin Lab Med 7(3) (1987) 587-606.
[57] R. Furst, I. Zundorf, T. Dingermann, New Knowledge About Old Drugs: The Anti-Inflammatory Properties of Cardiac Glycosides, Planta Med 83(12-13) (2017) 977-984.
[58] H. Li, H.H. Yang, Z.G. Sun, H.B. Tang, J.K. Min, Whole-transcriptome sequencing of knee joint cartilage from osteoarthritis patients, Bone Joint Res 8(7) (2019) 290-303.
[59] A.S. Lee, M.B. Ellman, D. Yan, J.S. Kroin, B.J. Cole, A.J. van Wijnen, H.J. Im, A current review of molecular mechanisms regarding osteoarthritis and pain, Gene 527(2) (2013) 440-7.
[60] H.J. Im, X. Li, P. Muddasani, G.H. Kim, F. Davis, J. Rangan, C.B. Forsyth, M. Ellman, E.J. Thonar, Basic fibroblast growth factor accelerates matrix degradation via a neuro-endocrine pathway in human adult articular chondrocytes, J Cell Physiol 215(2) (2008) 452-63.
[61] J. Shen, Y. Abu-Amer, R.J. O'Keefe, A. McAlinden, Inflammation and epigenetic regulation in osteoarthritis, Connect Tissue Res 58(1) (2017) 49-63.
[62] M.B. Goldring, M. Otero, Inflammation in osteoarthritis, Curr Opin Rheumatol 23(5) (2011) 471-8.
[63] D. Chen, J. Shen, W. Zhao, T. Wang, L. Han, J.L. Hamilton, H.J. Im, Osteoarthritis: toward a comprehensive understanding of pathological mechanism, Bone Res 5 (2017) 16044.
[64] J.W. Singer, A. Fleischman, S. Al-Fayoumi, J.O. Mascarenhas, Q. Yu, A. Agarwal, Inhibition of interleukin-1 receptor-associated kinase 1 (IRAK1) as a therapeutic strategy, Oncotarget 9(70) (2018) 33416-33439.
[65] M. Grunke, H. Schulze-Koops, Successful treatment of inflammatory knee osteoarthritis with tumour necrosis factor blockade, Ann Rheum Dis 65(4) (2006) 555-6.
[66] D. Brenn, F. Richter, H.G. Schaible, Sensitization of unmyelinated sensory fibers of the joint nerve to mechanical stimuli by interleukin-6 in the rat: an inflammatory mechanism of joint pain, Arthritis Rheum 56(1) (2007) 351-9.
[67] T. Pap, J. Bertrand, Syndecans in cartilage breakdown and synovial inflammation, Nat Rev Rheumatol 9(1) (2013) 43-55.
[68] A. Mathiessen, P.G. Conaghan, Synovitis in osteoarthritis: current understanding with therapeutic implications, Arthritis Res Ther 19(1) (2017) 18.
[69] M.B. Goldring, Articular cartilage degradation in osteoarthritis, HSS J 8(1) (2012) 7-9.
[70] M. Karin, Z. Liu, E. Zandi, AP-1 function and regulation, Curr Opin Cell Biol 9(2) (1997) 240-6.
[71] P.W. Vesely, P.B. Staber, G. Hoefler, L. Kenner, Translational regulation mechanisms of AP-1 proteins, Mutat Res 682(1) (2009) 7-12.
[72] E. Shaulian, M. Karin, AP-1 in cell proliferation and survival, Oncogene 20(19) (2001) 2390-400.
[73] M. Kappelmann, A. Bosserhoff, S. Kuphal, AP-1/c-Jun transcription factors: regulation and function in malignant melanoma, Eur J Cell Biol 93(1-2) (2014) 76-81.
[74] J.J. Ventura, N.J. Kennedy, R.A. Flavell, R.J. Davis, JNK regulates autocrine expression of TGF-beta1, Mol Cell 15(2) (2004) 269-78.
[75] J. Soul, T.E. Hardingham, R.P. Boot-Handford, J.M. Schwartz, SkeletalVis: an exploration and meta-analysis data portal of cross-species skeletal transcriptomics data, Bioinformatics 35(13) (2019) 2283-2290.
[76] N. Martin, O. Soriani, D. Bernard, Cardiac Glycosides as Senolytic Compounds, Trends Mol Med 26(3) (2020) 243-245.
[77] S. He, N.E. Sharpless, Senescence in Health and Disease, Cell 169(6) (2017) 1000-1011.
[78] M. Paez-Ribes, E. Gonzalez-Gualda, G.J. Doherty, D. Munoz-Espin, Targeting senescent cells in translational medicine, EMBO Mol Med 11(12) (2019) e10234.