Pyruvate Dehydrogenase Kinase 1 inhibition mediated oxidative phosphorylation enhancement in cartilage promotes osteoarthritis progression

作者全名："Yang, Xian; Jiang, Qingsong; Luan, Tiankuo; Yu, Chao; Liu, Zhibo; Wang, Ting; Wan, Jingyuan; Huang, Jiayu; Li, Ke"

作者地址："[Yang, Xian; Jiang, Qingsong; Wan, Jingyuan] Chongqing Med Univ, Dept Pharmacol, Chongqing, Peoples R China; [Luan, Tiankuo] Chongqing Med Univ, Basic Med Sch, Dept Human Anat, Chongqing, Peoples R China; [Yu, Chao] Chongqing Med Univ, Univ Town Hosp, Dept Orthoped Surg, Chongqing, Peoples R China; [Liu, Zhibo; Wang, Ting] Second Affiliated Hosp Chongqing, Dept Orthoped Surg, Chongqing, Peoples R China; [Huang, Jiayu] First Affiliated Hosp Chongqing, Reprod Med Ctr, Chongqing, Peoples R China; [Li, Ke] Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped Surg, Chongqing, Peoples R China; [Li, Ke] Chongqing Med Univ, Orthoped Lab, Chongqing, Peoples R China"

通信作者："Huang, JY (通讯作者)，First Affiliated Hosp Chongqing, Reprod Med Ctr, Chongqing, Peoples R China.; Li, K (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Orthoped Surg, Chongqing, Peoples R China.; Li, K (通讯作者)，Chongqing Med Univ, Orthoped Lab, Chongqing, Peoples R China."

来源：BMC MUSCULOSKELETAL DISORDERS

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001029987100004

JCR分区：Q2

影响因子：2.2

年份：2023

卷号：24

期号：1

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结束页：　

文献类型：Article

关键词：Osteoarthritis; PDK1; ECM; Glucose metabolism; Inflammation

摘要："Osteoarthritis (OA) is a common disease characterized by cartilage degradation. Growing evidence showed that glucose metabolism impacts joint homeostasis and an imbalance between glycolysis and oxidative phosphorylation (OXPHOS) may exacerbate OA progression, however, a definitive link is yet to be established. Here, we report that pyruvate metabolism and oxidative phosphorylation pathway is enriched in OA cartilage through gene set enrichment analysis (GSEA) and expression of Pyruvate Dehydrogenase Kinase 1 (PDK1), an enzyme that can phosphorylate Pyruvate Dehydrogenase (PDH), and inhibit pyruvate fluxes into the tricarboxylic acid (TCA) cycle and to OXPHOS, in articular cartilage is notably reduced through destabilization of medial meniscus (DMM). Moreover, by inhibiting PDK1, cartilage loss is markedly accelerated in DMM-induced OA through extracellular matrix (ECM) degradation and apoptosis of chondrocytes. These results indicate that PDK1 is involved in the progression of OA through accelerating cartilage matrix degradation and synovium inflammation to ameliorate cartilage degeneration."

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