Integrative Metabolic Pathway Analysis Reveals Novel Therapeutic Targets in Osteoarthritis
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Integrative Metabolic Pathway Analysis Reveals Novel Therapeutic Targets in OsteoarthritisAuthor(s)
Date
2020-01-24Citation
Rocha B, Cillero-Pastor B, Eijkel G, Calamia V, Fernández-Puente P, Paine MRL, et al. Integrative metabolic pathway analysis reveals novel therapeutic targets in osteoarthritis. Mol Cell Proteomics. 2020;19(4):574-588
Abstract
[Abstract] 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.
Keywords
Imaging
Cell biology
Cell differentiation
Immunohistochemistry
Metabolites
Chondrocytes
Chondrogenesis
Osteoarthritis
Cell biology
Cell differentiation
Immunohistochemistry
Metabolites
Chondrocytes
Chondrogenesis
Osteoarthritis
Description
Data availability: The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository (https://www.ebi.ac.uk/pride/archive/projects/PXD012879) with the dataset identifier PXD012879 and the project name of MSCs OA SILAC Mass spectrometry imaging
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Atribución 4.0 Internacional (CC BY 4.0) This research was originally published in Molecular and Cellular Proteomics © the American Society for Biochemistry and Molecular Biology
ISSN
1535-9476