PMID- 29356574 OWN - NLM STAT- MEDLINE DCOM- 20180417 LR - 20180417 IS - 1557-7430 (Electronic) IS - 1044-5498 (Linking) VI - 37 IP - 3 DP - 2018 Mar TI - Pyruvate Kinase M2 Modulates the Glycolysis of Chondrocyte and Extracellular Matrix in Osteoarthritis. PG - 271-277 LID - 10.1089/dna.2017.4048 [doi] AB - Pyruvate kinase M2 (PKM2) has been wildly verified to modulate glycolysis in tumor cells. However, the role of PKM2 on the glycolysis of osteoarthritis (OA) chondrocytes is still unclear. In present study, we investigate the function of PKM2 on OA chondrocyte glycolysis and the collagen matrix generation in vitro. Results showed that PKM2 was upregulated in OA chondrocytes compared with healthy control chondrocytes. In OA chondrocytes, ATP expression was lower compared with healthy control chondrocytes. Loss-of-function experiment showed that PKM2 knockdown mediated by lentivirus transfection could significantly suppress the glucose consumption and lactate secretion levels and decrease glucose transporter-1 (Glut-1), lactate dehydrogenase A (LDHA), and hypoxia inducible factor 1-alpha (HIF-1alpha), indicating the inhibition of PKM2 knockdown on glycolysis. Moreover, Cell Counting Kit-8 (CCK-8), flow cytometry, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay showed that PKM2 knockdown inhibited OA chondrocyte proliferation and promoted the apoptosis. Western blot and immunocytochemical staining showed that PKM2 knockdown downregulated the expression levels of COL2A1 and SOX-9. In summary, our results conclude that PKM2 modulates the glycolysis and extracellular matrix generation, providing the vital role of PKM2 on OA pathogenesis and a novel therapeutic target for OA. FAU - Yang, Xiaobo AU - Yang X AD - The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China . FAU - Chen, Weiping AU - Chen W AD - The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China . FAU - Zhao, Xiang AU - Zhao X AD - The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China . FAU - Chen, Linwei AU - Chen L AD - The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China . FAU - Li, Wanli AU - Li W AD - The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China . FAU - Ran, Jisheng AU - Ran J AD - The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China . FAU - Wu, Lidong AU - Wu L AD - The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, China . LA - eng PT - Journal Article DEP - 20180122 PL - United States TA - DNA Cell Biol JT - DNA and cell biology JID - 9004522 RN - EC 2.7.1.40 (Pyruvate Kinase) SB - IM MH - Adult MH - Cell Proliferation MH - Cells, Cultured MH - Chondrocytes/*enzymology MH - Enzyme Induction MH - Extracellular Matrix/*enzymology MH - *Glycolysis MH - Humans MH - Middle Aged MH - Osteoarthritis, Knee/*enzymology/pathology MH - Pyruvate Kinase/*physiology MH - Up-Regulation OTO - NOTNLM OT - PKM2 OT - chondrocyte OT - extracellular matrix OT - glycolysis OT - osteoarthritis EDAT- 2018/01/23 06:00 MHDA- 2018/04/18 06:00 CRDT- 2018/01/23 06:00 PHST- 2018/01/23 06:00 [pubmed] PHST- 2018/04/18 06:00 [medline] PHST- 2018/01/23 06:00 [entrez] AID - 10.1089/dna.2017.4048 [doi] PST - ppublish SO - DNA Cell Biol. 2018 Mar;37(3):271-277. doi: 10.1089/dna.2017.4048. Epub 2018 Jan 22.