Glucose metabolism is fundamental for the functions of all tissues,including cartilage.Despite the emerging evidence related to glucose metabolism in the regulation of prenatal cartilage development,little is known ab...Glucose metabolism is fundamental for the functions of all tissues,including cartilage.Despite the emerging evidence related to glucose metabolism in the regulation of prenatal cartilage development,little is known about the role of glucose metabolism and its biochemical basis in postnatal cartilage growth and homeostasis.We show here that genetic deletion of the glucose transporter Glutl in postnatal cartilage impairs cell proliferation and matrix production in growth plate(GPs)but paradoxically increases cartilage remnants in the metaphysis,resulting in shortening of long bones.On the other hand,articular cartilage(AC)with Glutl deficiency presents diminished cellularity and loss of proteoglycans,which ultimately progress to cartilage fibrosis.Moreover,predisposition to Glutl deficiency severely exacerbates injury-induced osteoarthritis.Regardless of the disparities in glucose metabolism between GP and AC chondrocytes under normal conditions,both types of chondrocytes demonstrate metabolic plasticity to enhance glutamine utilization and oxidation in the absence of glucose availability.However,uncontrolled glutamine flux causes collagen overmodification,thus affecting extracellular matrix remodeling in both cartilage compartments.These results uncover the pivotal and distinct roles of Glutl-mediated glucose metabolism in two of the postnatal cartilage compartments and link some cartilage abnormalities to altered glucose/glutamine metabolism.展开更多
基金This work was supported by the following NIH/NIAMS grants:R01 grants(AR069605 and AR079100 to RJ.O.as well as AR075860 and AR077616 to J.S.),an R21 grant(AR077226 to J.S.),a P30 Core Center grant(AR057235 to Musculoskeletal Research Center)an NCI grant(R35ES028365 to G.P.).
文摘Glucose metabolism is fundamental for the functions of all tissues,including cartilage.Despite the emerging evidence related to glucose metabolism in the regulation of prenatal cartilage development,little is known about the role of glucose metabolism and its biochemical basis in postnatal cartilage growth and homeostasis.We show here that genetic deletion of the glucose transporter Glutl in postnatal cartilage impairs cell proliferation and matrix production in growth plate(GPs)but paradoxically increases cartilage remnants in the metaphysis,resulting in shortening of long bones.On the other hand,articular cartilage(AC)with Glutl deficiency presents diminished cellularity and loss of proteoglycans,which ultimately progress to cartilage fibrosis.Moreover,predisposition to Glutl deficiency severely exacerbates injury-induced osteoarthritis.Regardless of the disparities in glucose metabolism between GP and AC chondrocytes under normal conditions,both types of chondrocytes demonstrate metabolic plasticity to enhance glutamine utilization and oxidation in the absence of glucose availability.However,uncontrolled glutamine flux causes collagen overmodification,thus affecting extracellular matrix remodeling in both cartilage compartments.These results uncover the pivotal and distinct roles of Glutl-mediated glucose metabolism in two of the postnatal cartilage compartments and link some cartilage abnormalities to altered glucose/glutamine metabolism.
