软骨发生
细胞培养中氨基酸的稳定同位素标记
骨关节炎
间充质干细胞
软骨
细胞外基质
化学
细胞生物学
代谢组学
再生(生物学)
透明质酸
代谢途径
蛋白质组学
生物化学
生物
新陈代谢
医学
病理
解剖
基因
替代医学
色谱法
作者
Beatriz Rocha,Berta Cillero‐Pastor,Gert B. Eijkel,V. Calamia,Patricia Fernández-Puente,Martin R. L. Paine,Cristina Ruiz-Romero,Ron M. A. Heeren,Francisco J. Blanco
标识
DOI:10.1074/mcp.ra119.001821
摘要
In osteoarthritis (OA), impairment of cartilage regeneration can be related to a defective chondrogenic differentiation of mesenchymal stromal cells (MSCs). Therefore, understanding the proteomic- and metabolomic-associated molecular events during the chondrogenesis of MSCs could provide alternative targets for therapeutic intervention. Here, a SILAC-based proteomic analysis identified 43 proteins related with metabolic pathways whose abundance was significantly altered during the chondrogenesis of OA human bone marrow MSCs (hBMSCs). Then, the level and distribution of metabolites was analyzed in these cells and healthy controls by matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), leading to the recognition of characteristic metabolomic profiles at the early stages of differentiation. Finally, integrative pathway analysis showed that UDP-glucuronic acid synthesis and amino sugar metabolism were downregulated in OA hBMSCs during chondrogenesis compared with healthy cells. Alterations in these metabolic pathways may disturb the production of hyaluronic acid (HA) and other relevant cartilage extracellular matrix (ECM) components. This work provides a novel integrative insight into the molecular alterations of osteoarthritic MSCs and potential therapeutic targets for OA drug development through the enhancement of chondrogenesis.
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