Integrative Metabolic Pathway Analysis Reveals Novel Therapeutic Targets in Osteoarthritis

Beatriz Rocha, Berta Cillero-Pastor, Gert Eijkel, Valentina Calamia*, Patricia Fernandez-Puente, Martin R. L. Paine, Cristina Ruiz-Romero, Ron M. A. Heeren, Francisco J. Blanco*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Web of Science)

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.

Original languageEnglish
Pages (from-to)574-588
Number of pages15
JournalMolecular & Cellular Proteomics
Volume19
Issue number4
DOIs
Publication statusPublished - Apr 2020

Keywords

  • MESENCHYMAL STEM-CELLS
  • UDP-GLUCOSE DEHYDROGENASE
  • SYNOVIAL-FLUID INCREASE
  • CHONDROGENIC DIFFERENTIATION
  • MASS-SPECTROMETRY
  • BONE-MARROW
  • OSTEOGENIC DIFFERENTIATION
  • QUANTITATIVE PROTEOMICS
  • N-ACETYLGLUCOSAMINE
  • PROLIFERATION

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