Salinas Daniel, Minor Cody A, Carlson Ross P, McCutchen Carley N, Mumey Brendan M, June Ronald K
Computer Science, Montana State University, Bozeman, MT United States of America.
Mathematics, Montana State University, Bozeman, MT United States of America.
PLoS One. 2017 Jan 5;12(1):e0168326. doi: 10.1371/journal.pone.0168326. eCollection 2017.
Osteoarthritis is a debilitating disease likely involving altered metabolism of the chondrocytes in articular cartilage. Chondrocytes can respond metabolically to mechanical loads via cellular mechanotransduction, and metabolic changes are significant because they produce the precursors to the tissue matrix necessary for cartilage health. However, a comprehensive understanding of how energy metabolism changes with loading remains elusive. To improve our understanding of chondrocyte mechanotransduction, we developed a computational model to calculate the rate of reactions (i.e. flux) across multiple components of central energy metabolism based on experimental data. We calculated average reaction flux profiles of central metabolism for SW1353 human chondrocytes subjected to dynamic compression for 30 minutes. The profiles were obtained solving a bounded variable linear least squares problem, representing the stoichiometry of human central energy metabolism. Compression synchronized chondrocyte energy metabolism. These data are consistent with dynamic compression inducing early time changes in central energy metabolism geared towards more active protein synthesis. Furthermore, this analysis demonstrates the utility of combining targeted metabolomic data with a computational model to enable rapid analysis of cellular energy utilization.
骨关节炎是一种使人衰弱的疾病，可能涉及关节软骨中软骨细胞代谢的改变。软骨细胞可通过细胞机械转导对机械负荷产生代谢反应，而代谢变化意义重大，因为它们产生软骨健康所需组织基质的前体。然而，对于能量代谢如何随负荷变化仍缺乏全面的了解。为了增进我们对软骨细胞机械转导的理解，我们基于实验数据开发了一个计算模型，以计算跨中心能量代谢多个组分的反应速率（即通量）。我们计算了SW1353人软骨细胞在动态压缩30分钟后的中心代谢平均反应通量谱。这些谱是通过求解一个有界变量线性最小二乘问题获得的，该问题代表了人类中心能量代谢的化学计量关系。压缩使软骨细胞能量代谢同步。这些数据与动态压缩诱导中心能量代谢早期变化以促进更活跃的蛋白质合成一致。此外，该分析证明了将靶向代谢组学数据与计算模型相结合以快速分析细胞能量利用的实用性。
