Mechanotransduction in primary human osteoarthritic chondrocytes is mediated by metabolism of energy, lipids, and amino acids.
Mechanotransduction in primary human osteoarthritic chondrocytes is mediated by metabolism of energy, lipids, and amino acids.
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DOI：
10.1016/j.jbiomech.2015.10.038
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发表时间：
2015-12-16
影响因子：
2.4
通讯作者：
June RK
中科院分区：
文献类型：
--
作者：
Zignego DL;Hilmer JK;June RK
软骨细胞是在关节软骨中发现的唯一细胞类型，并且在体内反复经受机械负荷。我们假设，生理动态压缩的结果在能量代谢的变化，以产生蛋白质的细胞周围和细胞外基质的维护。本研究的目的是在短期内（<30分钟）深入了解。通过分析从骨关节炎供体的股骨头收获的人软骨细胞的代谢组学谱，研究软骨细胞对亚损伤的生理压缩的反应。将细胞接种的琼脂糖构建体随机分配到实验组，并施加动态压缩0、15或30分钟。动态压缩后，提取代谢物并通过HPLC-MS检测。非靶向分析检查了全局代谢组学特征的变化，靶向分析检查了与中心能量代谢相关的特定代谢物的表达。我们确定了数百种受压缩调节的代谢物，并报告了在现有代谢物数据库中未发现的16种分子的检测结果。我们观察到患者特异性机械转导与老化依赖性。有针对性的研究发现，NADP+与NADPH的比率短暂增加，GDP与GTP的比率最初降低，表明能量流入TCA循环。通过表征初级软骨细胞对施加动态压缩的代谢组学特征，本研究提供了对OA软骨细胞如何响应机械负荷的深入了解。这些结果与机械诱导的信号传导导致的糖酵解能量利用增加一致，并为软骨细胞如何抵抗机械负荷的复杂图像增加了大量新数据。
Chondrocytes are the sole cell type found in articular cartilage and are repeatedly subjected to mechanical loading in vivo. We hypothesized that physiological dynamic compression results in changes in energy metabolism to produce proteins for maintenance of the pericellular and extracellular matrices. The objective of this study was to develop an in-depth understanding for the short term (<30 min.) chondrocyte response to sub-injurious, physiological compression by analyzing metabolomic profiles for human chondrocytes harvested from femoral heads of osteoarthritic donors. Cell-seeded agarose constructs were randomly assigned to experimental groups, and dynamic compression was applied for 0, 15, or 30 minutes. Following dynamic compression, metabolites were extracted and detected by HPLC-MS. Untargeted analyses examined changes in global metabolomics profiles and targeted analysis examined the expression of specific metabolites related to central energy metabolism. We identified hundreds of metabolites that were regulated by applied compression, and we report the detection of 16 molecules not found in existing metabolite databases. We observed patient-specific mechanotransduction with aging dependence. Targeted studies found a transient increase in the ratio of NADP+ to NADPH and an initial decrease in the ratio of GDP to GTP, suggesting a flux of energy into the TCA cycle. By characterizing metabolomics profiles of primary chondrocytes in response to applied dynamic compression, this study provides insight into how OA chondrocytes respond to mechanical load. These results are consistent with increases in glycolytic energy utilization by mechanically induced signaling, and add substantial new data to a complex picture of how chondrocytes transduce mechanical loads.
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影响因子：
5.5
作者：
Grygorczyk, Ryszard;Furuya, Kishio;Sokabe, Masahiro
通讯作者：
Sokabe, Masahiro
影响因子：
4.3
作者：
Cavill R;Kamburov A;Ellis JK;Athersuch TJ;Blagrove MS;Herwig R;Ebbels TM;Keun HC
通讯作者：
Keun HC
影响因子：
3.3
作者：
Sophia Fox AJ;Bedi A;Rodeo SA
通讯作者：
Rodeo SA
影响因子：
64.8
作者：
GRODZINSKY, AJ;LIPSHITZ, H;GLIMCHER, MJ
通讯作者：
GLIMCHER, MJ
影响因子：
7
作者：
De Croos, J. N. A.;Jang, B.;Kandel, R. A.
通讯作者：
Kandel, R. A.