{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:45:37Z","timestamp":1792784737998,"version":"4.5.0"},"reference-count":39,"publisher":"American Chemical Society (ACS)","issue":"10","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"name":"Youth Project of the Shandong Provincial Natural Science Foundation","award":["ZR2022QH208"],"award-info":[{"award-number":["ZR2022QH208"]}]},{"name":"General Project of the Shandong Provincial Medical and Health Science and Technology Development Plan","award":["202304071516"],"award-info":[{"award-number":["202304071516"]}]},{"name":"National Natural Science Foundation of China (NSFC)","award":["82575087"],"award-info":[{"award-number":["82575087"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Youth Project of the National Natural Science Foundation of China","award":["82104897"],"award-info":[{"award-number":["82104897"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,10,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Nonhistone acetylation is a key epigenetic mechanism in osteoarthritis (OA), but its specific role in cartilage degeneration remains unclear. Here, we integrated transcriptomics, proteomics, and acetyl-proteomics to systematically analyze molecular changes in rat OA cartilage. Multiomics coenrichment identified the ECM-receptor interaction pathway as the core target, reprogrammed by increased acetylation of Fn1, Tnc, and Itgb1. Using 113 machine-learning strategies, we identified 11 core diagnostic genes, with Wisp3 showing the highest efficacy validated in independent data sets. In vitro experiments and single-cell RNA-seq confirmed that Wisp3 downregulation disrupts ECM homeostasis. This study reveals that nonhistone acetylation drives OA by reprogramming the ECM-receptor interaction pathway and provides novel early diagnostic biomarkers.<\/jats:p>","DOI":"10.1021\/acs.jproteome.6c00137","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:49:57Z","timestamp":1788263397000},"page":"5127-5145","source":"Crossref","is-referenced-by-count":0,"title":["Nonhistone\nProtein Acetylation Reprograms the ECM-Receptor\nInteraction Pathway: Multiomics Profiling of Cartilage Degeneration\nin Rat Models of Osteoarthritis"],"prefix":"10.1021","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9475-3518","authenticated-orcid":true,"given":"Jiahao","family":"Sun","sequence":"first","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine , , ,","place":["Jinan, Shandong, China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5918-1721","authenticated-orcid":true,"given":"Teng","family":"Ma","sequence":"additional","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine , , ,","place":["Jinan, Shandong, China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Sun","sequence":"additional","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine , , ,","place":["Jinan, Shandong, China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu","family":"Cui","sequence":"additional","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine , , ,","place":["Jinan, Shandong, China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ximin","family":"Jin","sequence":"additional","affiliation":[{"name":"Shandong University of Traditional Chinese Medicine , , ,","place":["Jinan, Shandong, China, 250014"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongkui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Shandong University of Traditional Chinese Medicine , , ,","place":["Jinan, Shandong, China, 250011"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenpeng","family":"Xie","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Shandong University of Traditional Chinese Medicine , , ,","place":["Jinan, Shandong, China, 250011"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"issue":"8","key":"2026100208412579900_cit1","doi-asserted-by":"publisher","first-page":"194","DOI":"10.3390\/biology9080194","article-title":"Pathogenesis of Osteoarthritis: Risk Factors,\nRegulatory Pathways in Chondrocytes, and Experimental Models","volume":"9","author":"He","year":"2020","journal-title":"Biology"},{"issue":"2","key":"2026100208412579900_cit2","doi-asserted-by":"publisher","first-page":"101836","DOI":"10.1016\/j.berh.2023.101836","article-title":"The burden\nof osteoarthritis: Is it a rising problem?","volume":"37","author":"Scheuing","year":"2023","journal-title":"Best Pract. Res., Clin. Rheumatol."},{"issue":"1","key":"2026100208412579900_cit3","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41392-023-01330-w","article-title":"Osteoarthritis: pathogenic\nsignaling pathways and therapeutic targets","volume":"8","author":"Yao","year":"2023","journal-title":"Signal Transduction Targeted Ther."},{"issue":"2","key":"2026100208412579900_cit4","doi-asserted-by":"publisher","DOI":"10.1002\/wnan.1844","article-title":"New insights\nin osteoarthritis diagnosis and treatment: Nano-strategies for an\nimproved disease management","volume":"15","author":"Paesa","year":"2023","journal-title":"Wiley Interdiscip.\nRev.: nanomed. Nanobiotechnol."},{"key":"2026100208412579900_cit5","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1038\/s41572-025-00594-6","article-title":"Osteoarthritis","volume":"11","author":"Tang","year":"2025","journal-title":"Nat. Rev. Dis. Primers"},{"issue":"31","key":"2026100208412579900_cit6","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adf1130","article-title":"Adseverin, an actin-binding\nprotein, modulates hypertrophic chondrocyte differentiation and osteoarthritis\nprogression","volume":"9","author":"Chan","year":"2023","journal-title":"Sci. Adv."},{"issue":"3","key":"2026100208412579900_cit7","doi-asserted-by":"publisher","first-page":"04855","DOI":"10.3892\/ijmm.2021.4855","article-title":"Dihydroartemisinin attenuates osteoarthritis by inhibiting abnormal\nbone remodeling and angiogenesis in subchondral bone","volume":"47","author":"Ma","year":"2021","journal-title":"Int. J. Mol. Med."},{"issue":"9","key":"2026100208412579900_cit8","doi-asserted-by":"publisher","first-page":"1061","DOI":"10.1016\/j.joca.2007.03.006","article-title":"The surgical\ndestabilization of the\nmedial meniscus (DMM) model of osteoarthritis in the 129\/SvEv mouse","volume":"15","author":"Glasson","year":"2007","journal-title":"Osteoarthritis Cartilage"},{"issue":"2","key":"2026100208412579900_cit9","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1007\/s11684-024-1061-y","article-title":"Pathological progression\nof osteoarthritis: a perspective on subchondral bone","volume":"18","author":"Li","year":"2024","journal-title":"Front. Med."},{"key":"2026100208412579900_cit10","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.jot.2025.05.005","article-title":"Construction\nof cartilaginous organoids based\non cartilage extracellular matrix microcarriers to promote articular\ncartilage regeneration through immune regulation","volume":"53","author":"Jiang","year":"2025","journal-title":"J. Orthop. Translat."},{"issue":"1","key":"2026100208412579900_cit11","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/s41467-023-35795-8","article-title":"Control\nof protein\nstability by post-translational modifications","volume":"14","author":"Lee","year":"2023","journal-title":"Nat. Commun."},{"key":"2026100208412579900_cit12","doi-asserted-by":"publisher","first-page":"100729","DOI":"10.1016\/j.drup.2020.100729","article-title":"The key roles of\nthe lysine acetyltransferases KAT6A\nand KAT6B in physiology and pathology","volume":"53","author":"Wiesel-Motiuk","year":"2020","journal-title":"Drug\nResistance Updates"},{"issue":"3","key":"2026100208412579900_cit13","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1038\/s41580-018-0081-3","article-title":"Functions and mechanisms of non-histone\nprotein acetylation","volume":"20","author":"Narita","year":"2019","journal-title":"Nat. Rev. Mol. Cell Biol."},{"issue":"3","key":"2026100208412579900_cit14","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1111\/acel.12456","article-title":"Acetylation reduces\nSOX9 nuclear entry and ACAN gene transactivation in human chondrocytes","volume":"15","author":"Bar Oz","year":"2016","journal-title":"Aging Cell"},{"issue":"3","key":"2026100208412579900_cit15","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/j.joca.2018.11.008","article-title":"StormsL,et al.Increased susceptibility to develop spontaneous\nand post-traumatic osteoarthritis in Dot1l-deficient mice.Osteoarthritis\nCartilage","volume":"27","author":"CornelisF","year":"2019","journal-title":"Osteoarthritis Cartilage"},{"issue":"3","key":"2026100208412579900_cit16","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1002\/jor.23322","article-title":"HeardBJ,et al.Use\nof pre-clinical surgically induced\nmodels to understand biomechanical and biological consequences of\nPTOA development.J Orthop Res","volume":"35","author":"Barton","year":"2017","journal-title":"J. Orthop. Res."},{"issue":"D1","key":"2026100208412579900_cit17","doi-asserted-by":"publisher","first-page":"D672","DOI":"10.1093\/nar\/gkae909","article-title":"KEGG: biological\nsystems database as a model of the real world","volume":"53","author":"Kanehisa","year":"2025","journal-title":"Nucleic Acids Res."},{"issue":"2","key":"2026100208412579900_cit18","doi-asserted-by":"publisher","DOI":"10.15252\/embr.202050967","article-title":"Histone acetyltransferase\n1 is a succinyltransferase for histones and non-histones and promotes\ntumorigenesis","volume":"22","author":"Yang","year":"2021","journal-title":"EMBO Rep."},{"issue":"1","key":"2026100208412579900_cit19","doi-asserted-by":"publisher","first-page":"6628","DOI":"10.1038\/s41467-022-34399-y","article-title":"YiaC and\nCobB regulate\nlysine lactylation in Escherichia coli","volume":"13","author":"Dong","year":"2022","journal-title":"Nat.\nCommun."},{"issue":"1","key":"2026100208412579900_cit20","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.joca.2021.05.007","article-title":"The burden\nof OA-health services\nand economics","volume":"30","author":"Leifer","year":"2022","journal-title":"Osteoarthritis Cartilage"},{"key":"2026100208412579900_cit21","doi-asserted-by":"publisher","first-page":"648459","DOI":"10.1155\/2014\/648459","article-title":"The ECM-cell interaction of cartilage extracellular\nmatrix on chondrocytes","author":"Gao","year":"2014","journal-title":"Biomed. Res. Int."},{"issue":"6633","key":"2026100208412579900_cit22","doi-asserted-by":"publisher","DOI":"10.1126\/science.abp8964","article-title":"The extracellular matrix and the\nimmune system: A mutually dependent relationship","volume":"379","author":"Sutherland","year":"2023","journal-title":"Science"},{"issue":"4","key":"2026100208412579900_cit23","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1016\/j.immuni.2024.03.002","article-title":"DAMPs and DAMP-sensing receptors\nin inflammation and diseases","volume":"57","author":"Ma","year":"2024","journal-title":"Immunity"},{"issue":"9","key":"2026100208412579900_cit24","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1038\/nrm3416","article-title":"Transduction of mechanical and cytoskeletal\ncues by YAP and TAZ","volume":"13","author":"Halder","year":"2012","journal-title":"Nat. Rev. Mol. 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Cell Biol."},{"key":"2026100208412579900_cit28","doi-asserted-by":"publisher","first-page":"108908","DOI":"10.1016\/j.pharmthera.2025.108908","article-title":"The\nrole of lysine acetylation\nin metabolic sensing and proteostasis","volume":"274","author":"Eftekhari","journal-title":"Pharmacol.\nTher."},{"key":"2026100208412579900_cit29","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1186\/s42825-024-00160-y","article-title":"The potential of undenatured type II collagen against\narthritis:\na review","volume":"6","author":"Zhou","year":"2024","journal-title":"Collagen Leather"},{"issue":"1","key":"2026100208412579900_cit30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41392-022-01259-6","article-title":"Targeting\nintegrin pathways: mechanisms and advances in therapy","volume":"8","author":"Pang","year":"2023","journal-title":"Signal Transduction Targeted Ther"},{"issue":"1","key":"2026100208412579900_cit31","doi-asserted-by":"publisher","first-page":"703","DOI":"10.1038\/s41467-025-55960-5","article-title":"Illuminating the impact\nof N-terminal\nacetylation: from protein to physiology","volume":"16","author":"McTiernan","year":"2025","journal-title":"Nat.\nCommun."},{"issue":"3","key":"2026100208412579900_cit32","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.261","article-title":"Protein posttranslational\nmodifications in\nhealth and diseases: Functions, regulatory mechanisms, and therapeutic\nimplications","volume":"4","author":"Zhong","year":"2023","journal-title":"MedComm"},{"key":"2026100208412579900_cit33","doi-asserted-by":"publisher","first-page":"663978","DOI":"10.3389\/fphys.2021.663978","article-title":"Matrix Metalloproteinase\n3: A Promoting and Destabilizing Factor in the Pathogenesis of Disease\nand Cell Differentiation","volume":"12","author":"Wan","year":"2021","journal-title":"Front. Physiol."},{"issue":"15","key":"2026100208412579900_cit34","doi-asserted-by":"publisher","first-page":"7280","DOI":"10.1111\/jcmm.16757","article-title":"CCL7 contributes\nto angiotensin II-induced abdominal aortic aneurysm by promoting macrophage\ninfiltration and pro-inflammatory phenotype","volume":"25","author":"Xie","year":"2021","journal-title":"J. Cell. Mol. Med."},{"issue":"12","key":"2026100208412579900_cit35","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1517\/13543780903321490","article-title":"The p38 MAPK\ninhibitors for the treatment\nof inflammatory diseases and cancer","volume":"18","author":"Yong","year":"2009","journal-title":"Expert\nOpin. Invest. Drugs"},{"issue":"9","key":"2026100208412579900_cit36","doi-asserted-by":"publisher","first-page":"1286","DOI":"10.3390\/ph16091286","article-title":"Revisiting\np38 Mitogen-Activated Protein Kinases (MAPK) in Inflammatory Arthritis:\nA Narrative of the Emergence of MAPK-Activated Protein Kinase Inhibitors\n(MK2i)","volume":"16","author":"Ganguly","year":"2023","journal-title":"Pharmaceuticals"},{"issue":"12","key":"2026100208412579900_cit37","doi-asserted-by":"publisher","first-page":"1547","DOI":"10.1136\/ard-2023-224304","article-title":"Directed\ndifferentiation of human pluripotent stem\ncells into articular cartilage reveals effects caused by absence of\nWISP3, the gene responsible for progressive pseudorheumatoid arthropathy\nof childhood","volume":"82","author":"Li","year":"2023","journal-title":"Ann. Rheum Dis."},{"key":"2026100208412579900_cit38","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1038\/s12276-024-01243-w","article-title":"Big data and deep learning\nfor RNA biology","volume":"56","author":"Hwang","year":"2024","journal-title":"Exp. Mol. Med."},{"issue":"1","key":"2026100208412579900_cit39","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/s41577-022-00746-9","article-title":"IL-17\nand IL-17-producing cells in protection versus pathology","volume":"23","author":"Mills","year":"2023","journal-title":"Nat. Rev. Immunol."}],"container-title":["Journal of Proteome Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jproteome.6c00137","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/25\/10\/5127\/67426667\/acs.jproteome.6c00137.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jprobs\/article-pdf\/25\/10\/5127\/67426667\/acs.jproteome.6c00137.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T12:52:10Z","timestamp":1790945530000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jprobs\/article\/25\/10\/5127\/5330455\/Nonhistone-Protein-Acetylation-Reprograms-the-ECM"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,26]]},"references-count":39,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,8,26]]},"published-print":{"date-parts":[[2026,10,2]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jproteome.6c00137","relation":{},"ISSN":["1535-3893","1535-3907"],"issn-type":[{"value":"1535-3893","type":"print"},{"value":"1535-3907","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,26]]}}}