Cited by 43Osteoarthritis Treatment and MechanismsBone and Joint DiseasesMesenchymal stem cell research

Large-scale gene expression in bone marrow mesenchymal stem cells: a putative role for COL10A1 in osteoarthritis

Lamas, José Ramón, Rodríguez-Rodríguez, Luis, Vigo, Ana G, Álvarez-Lafuente, Roberto, López-Romero, Pedro, Marco, Fernando, Camafeita, Emilio, Dopazo, Ana +6 more·2010·Annals of the Rheumatic Diseases

Abstract

Objectives To elucidate disease-specific molecular changes occurring in osteoarthritis (OA) by analysing the differential gene expression profiles of bone marrow mesenchymal stem cells (BM-MSCs) from patients with OA compared with those without OA.Methods Expression profiles of BM-MSCs from eight paired patients with OA and patients with hip fracture without signs of OA were compared by DNA microarray expression analysis and significant differences were evaluated by computational Gene Set Enrichment Analysis. To validate the involvement of COL10A1 as part of the most downregulated gene set in OA, three tagging single nucleotide polymorphisms were genotyped in 191 patients with OA and 283 controls. COL10A1 expression was also assessed by quantitative RT-PCR in additional subjects.Results Expression levels in 9% (1967) of the overall transcripts were significantly different (p<0.05) between MSCs from patients with OA and controls (532 genes reached twofold differences: 240 were upregulated and 292 were downregulated). Cell development and differentiation were the functional categories accounting for most genes with altered expression. Interestingly, several genes related to the Wnt/-catenin pathway and collagen genes were downregulated in MSCs from patients with OA. The collagen gene set was clearly downregulated in OA. Furthermore, the expression of COL10A1 was significantly reduced in patients with OA. A genetic association between the COL10A1 rs11965969 polymorphism and OA was also found.Conclusion COL10A1 downregulation seems to have a role in the establishment of a defective and/or unstable subchondral cartilage matrix in OA disease. It is proposed that OA may be linked to the intrinsic defective regenerative potential of BM-MSCs resulting from its reduced expression of fate commitment-related genes.

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Crossref · 10.1136/ard.2009.122564

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Authors
Lamas, J. R., Rodríguez-Rodríguez, L., Vigo, A. G., Álvarez-Lafuente, R., López-Romero, P., Marco, F., Camafeita, E., Dopazo, A., Callejas, S., Villafuertes, E., Hoyas, J. A., Tornero-Esteban, M. P., Urcelay, E., & FernÁndez-Gutiérrez, B.
Affiliations
  • Hospital Clínico San Carlos (ES)
  • Spanish National Centre for Cardiovascular Research (ES)
Corresponding author
Lamas, José Ramón
Venue
Annals of the Rheumatic Diseases
Publisher
Elsevier BV
Published
2010-10
Volume
69
Issue
10
Pages
1880-1885
ISSN
0003-4967 (ISSN-L)
OpenAlex
W2127357116
Cited by
43
References
49
Citations by year
2025: 1 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 2 · 2014: 5 · 2013: 3 · 2012: 4
FWCI
2.91
Type
journal article
Language
en
Open access
closed
Locations
  • Annals of the Rheumatic Diseases (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone and Joint Diseases
  • Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
Keywords
osteoarthritis, bone marrow mesenchymal stem cells, COL10A1, gene expression profiling, collagen genes, genetic association, hip fracture, stem cell differentiation
MeSH terms
Adult, Aged, Aged, 80 and over, Bone Marrow Cells, Cells, Cultured, Gene Frequency, Humans, Middle Aged, Osteoarthritis, Cluster Analysis, Genetic Predisposition to Disease, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Gene Expression Profiling, Collagen Type X, Mesenchymal Stem Cells

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