{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T03:40:20Z","timestamp":1785814820676,"version":"3.56.0"},"reference-count":135,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260928"],"award-info":[{"award-number":["82260928"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82260928"],"award-info":[{"award-number":["82260928"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Yunnan Province Basic Research Special Key Project","award":["202301AS070076"],"award-info":[{"award-number":["202301AS070076"]}]},{"name":"Scientific Research Fund Project of the Yunnan Provincial Department of Education","award":["2025Y0620"],"award-info":[{"award-number":["2025Y0620"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is an autoimmune disease primarily characterized by chronic, erosive polyarthritis. It is associated with a high rate of disability, and its pathogenesis remains incompletely understood. Uncontrolled chronic inflammation, synovial hyperplasia, Pannus formation, and bone destruction in RA patients remain the core challenges facing current clinical treatment, and the inflammatory response is generally considered the initiating factor for this series of pathological processes. In an inflammatory environment, the body\u2019s metabolic rate accelerates, leading to increased local oxygen consumption and ultimately creating a hypoxic microenvironment. Research has shown that under hypoxic conditions, glycolysis serves as the body\u2019s primary energy pathway and is essential for sustaining the inflammatory response. Furthermore, lactate, a byproduct of glycolysis, functions not only as a metabolic byproduct but also as a precursor molecule; through lactylation, it contributes to the progression of RA. Although this metabolic\u2013epigenetic axis is a common feature of various chronic inflammatory diseases, its effects on joint pathology may contribute to RA progression. Therefore, this article focuses on the intrinsic connections among hypoxia, glycolysis, and lactylation, and systematically reviews the immunological and inflammatory mechanisms of glycolysis in RA, the relationship between glycolysis and synovial hyperplasia, Pannus formation, and bone destruction in RA, and the role of lactate modification in promoting the pathological progression of RA. It also summarizes the latest research advances in RA therapies targeting hypoxia, glycolysis, and lactate modification, aiming to provide a theoretical basis for a deeper understanding of the pathogenesis of RA and the development of targeted treatment strategies.<\/jats:p>","DOI":"10.3390\/cells15121122","type":"journal-article","created":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T09:49:55Z","timestamp":1782121795000},"page":"1122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanisms and Therapeutic Targets of Hypoxia-Mediated Modifications in Glycolysis and Lactylation in Rheumatoid Arthritis"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6254-5658","authenticated-orcid":false,"given":"Niqin","family":"Xiao","sequence":"first","affiliation":[{"name":"Yunnan University of Chinese Medicine, Kunming 650500, China"},{"name":"Joint Graduate School of Traditional Chinese Medicine of China, Suzhou 215105, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3165-7763","authenticated-orcid":false,"given":"Heguo","family":"Yan","sequence":"additional","affiliation":[{"name":"Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujiang","family":"Xi","sequence":"additional","affiliation":[{"name":"Yunnan University of Chinese Medicine, Kunming 650500, China"},{"name":"Joint Graduate School of Traditional Chinese Medicine of China, Suzhou 215105, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1006-0532","authenticated-orcid":false,"given":"Yundong","family":"Xu","sequence":"additional","affiliation":[{"name":"Yunnan University of Chinese Medicine, Kunming 650500, China"},{"name":"Joint Graduate School of Traditional Chinese Medicine of China, Suzhou 215105, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zhang","sequence":"additional","affiliation":[{"name":"Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaofu","family":"Li","sequence":"additional","affiliation":[{"name":"Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaohu","family":"Xie","sequence":"additional","affiliation":[{"name":"Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e070856","DOI":"10.1136\/bmj-2022-070856","article-title":"Therapeutic advances in rheumatoid arthritis","volume":"384","author":"Brown","year":"2024","journal-title":"BMJ"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e002387","DOI":"10.1136\/rmdopen-2022-002387","article-title":"\u2018Difficult to treat\u2019 rheumatoid arthritis: Current position and considerations for next steps","volume":"8","author":"Tan","year":"2022","journal-title":"RMD Open"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Wu, D., Luo, Y., Li, T., Zhao, X., Lv, T., Fang, G., Ou, P., Li, H., Luo, X., and Huang, A. 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