PFKL regulates chondrocyte glucose metabolism during engineered chondrogenesis under hypoxia
Refereed conference paper presented and published in conference proceedings

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AbstractBeing a highly organized avascular connective tissue, articular cartilage has very limited capacity for self-repair following injury or degeneration. Cartilage tissue engineering is considered as a promising approach for promoting articular cartilage repair. Chondrocytes are readily located in a hypoxic microenvironment during cartilage development or repair. Hypoxia inducible factor-1α (HIF-1α) is identified as a key mediator for cellular adaptation to hypoxia during chondrogenesis. However, the molecular mechanisms of hypoxia regulation on the coordination of chondrocyte differentiation and energy metabolism during cartilage tissue engineering remain unclear. Here, we examined the effects of hypoxia (2% O2) on chondrogenesis in an engineered three dimensional (3D) culture system. Hypoxia was shown to increase cartilaginous matrix synthesis and upregulate the expression of chondrogenic marker
genes and proteins in the micromass and 3D complex cultures. This was accompanied by increased glucose uptake and intracellular lactate production by chondrocytes. Supper array analysis revealed the alterations of gene profiles associated with glucose metabolism.
Phosphofructokinase, liver (PFKL) was shown to be significantly up-regulated under hypoxia than that under normoxia. Chromatin immunoprecipitation assay identified the putative binding site of HIF-1α on the promoter region of PFKL. Deletion of HIF-1α in chondrocytes downregulated PFKL expression. Interestingly, siRNA-mediated PFKL knockdown inhibited chondrocyte maturation and decreased glucose uptake of chondrocytes under hypoxia, suggesting the pivotal role of PFKL in chondrocyte differentiation and glucose metabolism. In a mouse osteochondral defect model, transplantation of engineered cartilage tissue under hypoxia enhanced articular cartilage repair indicated by increased chondrogenic differentiation, cartilaginous matrix synthesis and inhibited cartilage hypertrophy compared with that under normoxia. Our data suggest that hypoxia enhances engineered chondrogenesis through coordinating chondrogenic differentiation and glucose metabolism at least partially mediated by the HIF-1α/PFKL pathway.
All Author(s) ListZHAO Kai, ZHANG Fengjie, TSANG Wing Pui, CHAN Wai Yee, WAN Chao
Name of ConferenceThe 4th International Chinese Musculoskeletal Research Conference (ICMRC-2019)
Start Date of Conference09/08/2019
End Date of Conference12/08/2019
Place of ConferenceShenzhen
Country/Region of ConferenceChina
LanguagesEnglish-United Kingdom

Last updated on 2020-27-11 at 11:19