{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T16:49:17Z","timestamp":1788022157397,"version":"build-2784847793"},"reference-count":61,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T00:00:00Z","timestamp":1687910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science and Technology Council, Taiwan","award":["NSCT 110-2314-B-843-001"],"award-info":[{"award-number":["NSCT 110-2314-B-843-001"]}]},{"name":"National Science and Technology Council, Taiwan","award":["NSCT 111-2314-B-843-001"],"award-info":[{"award-number":["NSCT 111-2314-B-843-001"]}]},{"name":"National Science and Technology Council, Taiwan","award":["NSCT 109-2314-B-075"],"award-info":[{"award-number":["NSCT 109-2314-B-075"]}]},{"name":"National Science and Technology Council, Taiwan","award":["PS11204"],"award-info":[{"award-number":["PS11204"]}]},{"name":"Ping-Tung Christian Hospital","award":["NSCT 110-2314-B-843-001"],"award-info":[{"award-number":["NSCT 110-2314-B-843-001"]}]},{"name":"Ping-Tung Christian Hospital","award":["NSCT 111-2314-B-843-001"],"award-info":[{"award-number":["NSCT 111-2314-B-843-001"]}]},{"name":"Ping-Tung Christian Hospital","award":["NSCT 109-2314-B-075"],"award-info":[{"award-number":["NSCT 109-2314-B-075"]}]},{"name":"Ping-Tung Christian Hospital","award":["PS11204"],"award-info":[{"award-number":["PS11204"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Osteoarthritis (OA) is the most common form of arthritis and joint disorder worldwide. Metabolic reprogramming of osteoarthritic chondrocytes from oxidative phosphorylation to glycolysis results in the accumulation of lactate from glycolytic metabolite pyruvate by lactate dehydrogenase A (LDHA), leading to cartilage degeneration. In the present study, we investigated the protective effects of the intra-articular administration of oxamate (LDHA inhibitor) against OA development and glycolysis-related protein expression in experimental OA rats. The animals were randomly allocated into four groups: Sham, anterior cruciate ligament transection (ACLT), ACLT + oxamate (0.25 and 2.5 mg\/kg). Oxamate-treated groups received an intra-articular injection of oxamate once a week for 5 weeks. Intra-articular oxamate significantly reduced the weight-bearing defects and knee width in ACLT rats. Histopathological analyses showed that oxamate caused significantly less cartilage degeneration in the ACLT rats. Oxamate exerts hypertrophic effects in articular cartilage chondrocytes by inhibiting glucose transporter 1, glucose transporter 3, hexokinase II, pyruvate kinase M2, pyruvate dehydrogenase kinases 1 and 2, pyruvate dehydrogenase kinase 2, and LHDA. Further analysis revealed that oxamate significantly reduced chondrocyte apoptosis in articular cartilage. Oxamate attenuates nociception, inflammation, cartilage degradation, and chondrocyte apoptosis and possibly attenuates glycolysis-related protein expression in ACLT-induced OA rats. The present findings will facilitate future research on LDHA inhibitors in prevention strategies for OA progression.<\/jats:p>","DOI":"10.3390\/ijms241310770","type":"journal-article","created":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:41:45Z","timestamp":1687999305000},"page":"10770","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Intra-Articular Lactate Dehydrogenase A Inhibitor Oxamate Reduces Experimental Osteoarthritis and Nociception in Rats via Possible Alteration of Glycolysis-Related Protein Expression in Cartilage Tissue"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4411-044X","authenticated-orcid":false,"given":"Zhi-Hong","family":"Wen","sequence":"first","affiliation":[{"name":"Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"},{"name":"Institute of BioPharmaceutical Sciences, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Sung","family":"Sung","sequence":"additional","affiliation":[{"name":"Division of Pain Management, Department of Anesthesiology, Taipei Veterans General Hospital, Taipei 112201, Taiwan"},{"name":"School of Medicine, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Chun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Pingtung Christian Hospital, No. 60 Dalian Road, Pingtung 90059, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4791-6078","authenticated-orcid":false,"given":"Zhi-Kang","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"},{"name":"Department of Orthopedic Surgery, Kaohsiung Veterans General Hospital, Kaohsiung 81341, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Cheng","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"},{"name":"Department of Orthopedics, Asia University Hospital, Taichung 41354, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Yan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsi-Wen","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Tzu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 97002, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wu-Fu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan"},{"name":"Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen-Hsuan","family":"Jean","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Pingtung Christian Hospital, No. 60 Dalian Road, Pingtung 90059, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1146\/annurev.immunol.24.021605.090646","article-title":"Osteoimmunology: Interplay between the Immune System and Bone Metabolism","volume":"24","author":"Walsh","year":"2006","journal-title":"Annu. 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