Large-scale gene expression in bone marrow mesenchymal stem cells: a putative role for COL10A1 in osteoarthritis
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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In patients with osteoarthritis, expression of COL10A1 was significantly downregulated.
“In patients with osteoarthritis, expression of COL10A1 was significantly downregulated (28).”
From Common variants near FRK/COL10A1 and VEGFA are associated with advanced age-related macular degeneration (2011) · cites this paper as [28]
Cites
Multilineage potential of adult human mesenchymal stem cells
Pittenger, M. F., Mackay, A. M., Beck, S. C., Jaiswal, R. K., Douglas, R., Mosca, J. D., Moorman, M. A., Simonetti, D. W., Craig, S., & Marshak, D. R. (1999) · Science · doi:10.1126/science.284.5411.143 · Cited by 21,052 · see citing works
Arnett, F. C., Edworthy, S. M., Bloch, D. A., McShane, D. J., Fries, J. F., Cooper, N. S., Healey, L. A., Kaplan, S. R., Liang, M. H., Luthra, H. S., et al. (1988) · Arthritis & Rheumatism · doi:10.1002/art.1780310302 · Cited by 19,753 · see citing works
Bioconductor: open software development for computational biology and bioinformatics
Gentleman, R., Carey, V., Bates, D., Bolstad, B., Dettling, M., Dudoit, S., Ellis, B., Gautier, L., Ge, Y., Gentry, J., et al. (2004) · Genome Biology · doi:10.1186/gb-2004-5-10-r80 · Cited by 13,133 · see citing works
Altman, R., Asch, E., Bloch, D., Bole, G., Borenstein, D., Brandt, K., Christy, W., Cooke, T. D., Greenwald, R., Hochberg, M., et al. (1986) · Arthritis & Rheumatism · doi:10.1002/art.1780290816 · Cited by 6,777 · see citing works
Day, T. F., Guo, X., Garrett-Beal, L., & Yang, Y. (2005) · Developmental Cell · doi:10.1016/j.devcel.2005.03.016 · Cited by 1,616 · see citing works
Bruder, S. P., Jaiswal, N., & Haynesworth, S. E. (1997) · Journal of Cellular Biochemistry · doi:10.1002/(sici)1097-4644(199702)64:2 · Cited by 1,477 · see citing works
Tissue-engineered bone regeneration
Petite, H., Viateau, V., Bensaïd, W., Meunier, A., de Pollak, C., Bourguignon, M., Oudina, K., Sedel, L., & Guillemin, G. (2000) · Nature Biotechnology · doi:10.1038/79449 · Cited by 1,475 · see citing works
Systemic Delivery of Bone Marrow–Derived Mesenchymal Stem Cells to the Infarcted Myocardium
Barbash, I. M., Chouraqui, P., Baron, J., Feinberg, M. S., Etzion, S., Tessone, A., Miller, L., Guetta, E., Zipori, D., Kedes, L. H., et al. (2003) · Circulation · doi:10.1161/01.cir.0000084828.50310.6a · Cited by 1,196 · see citing works
Stem cell therapy in a caprine model of osteoarthritis
Murphy, M. J., Fink, D. J., Hunziker, E. B., & Barry, F. (2003) · Arthritis & Rheumatism · doi:10.1002/art.11365 · Cited by 1,103 · see citing works
Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery
Hofstetter, C. P., Schwarz, E. J., Hess, D. A., Widenfalk, J., Manira, A. E., Prockop, D. J., & Olson, L. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.042678299 · Cited by 967 · see citing works
Review: Mesenchymal Stem Cells: Cell–Based Reconstructive Therapy in Orthopedics
Caplan, A. I. (2005) · Tissue Engineering · doi:10.1089/ten.2005.11.1198 · Cited by 826 · see citing works
RNA processing and its regulation: global insights into biological networks
Licatalosi, D. D., & Darnell, R. B. (2009) · Nature Reviews Genetics · doi:10.1038/nrg2673 · Cited by 760 · see citing works
Adipogenesis and WNT signalling
Christodoulides, C., Lagathu, C., Sethi, J. K., & Vidal‐Puig, A. (2008) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2008.09.002 · Cited by 596 · see citing works
GENECODIS: a web-based tool for finding significant concurrent annotations in gene lists
Carmona‐Sáez, P., Chagoyen, M., Tirado, F., Carazo, J. M., & Pascual-Montano, A. (2007) · Genome biology · doi:10.1186/gb-2007-8-1-r3 · Cited by 591 · see citing works
Osteopontin: a versatile regulator of inflammation and biomineralization
Giachelli, C. M., & Steitz, S. A. (2000) · Matrix Biology · doi:10.1016/s0945-053x(00)00108-6 · Cited by 586 · see citing works
Yet more evidence that osteoarthritis is not a cartilage disease
Brandt, K. D., Radin, E. L., Dieppe, P. A., et al. (2006) · Annals of the Rheumatic Diseases · doi:10.1136/ard.2006.058347 · Cited by 487 · see citing works
Zhu, M., Tang, D., Wu, Q., Hao, S., Chen, M., Xie, C. L., Rosier, R. N., O’Keefe, R. J., Zuscik, M. J., & Chen, D. (2008) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.080901 · Cited by 480 · see citing works
Nogales‐Cadenas, R., Carmona‐Sáez, P., Vázquez, M., Vicente, C., Yang, X., Tirado, F., Carazo, J. M., & Pascual-Montano, A. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp416 · Cited by 438 · see citing works
Loughlin, J. A., Dowling, B., Chapman, K. E., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403456101 · Cited by 402 · see citing works
R-Spondin Family Members Regulate the Wnt Pathway by a Common Mechanism
Kim, K.-A., Wagle, M.-C., Tran, K., Zhan, X., Dixon, M., Liu, S., Gros, D., Korver, W., Yonkovich, S., Tomašević, N., et al. (2008) · Molecular Biology of the Cell · doi:10.1091/mbc.e08-02-0187 · Cited by 343 · see citing works
Tamamura, Y., Otani, T., Kanatani, N., Koyama, E., Kitagaki, J., Komori, T., Yamada, Y., Costantini, F. D., Wakisaka, S., Pacifici, M., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m414275200 · Cited by 334 · see citing works
Zheng, Q., Zhou, G. D., Morello, R., Chen, Y., Garcia-Rojas, X., & Lee, B. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200211089 · Cited by 327 · see citing works
RUNX transcription factors as key targets of TGF-β superfamily signaling
Ito, Y., & Miyazono, K. (2003) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(03)00007-8 · Cited by 324 · see citing works
Mesenchymal stem cells: innovative therapeutic tools for rheumatic diseases
Djouad, F., Bouffi, C., Ghannam, S., Noël, D., & Jørgensen, C. (2009) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2009.104 · Cited by 315 · see citing works
Aigner, T. G., Söder, S., Gebhard, P. M., McAlinden, A., & Haag, J. (2007) · Nature Clinical Practice Rheumatology · doi:10.1038/ncprheum0534 · Cited by 270 · see citing works
Tchetina, E. V., Squires, G. R., & Poole, A. R. (2005) · PubMed · Cited by 213 · see citing works
Baksh, D., Boland, G. M., & Tuan, R. S. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21097 · Cited by 174 · see citing works
Alfaro, M. P., Pagni, M., Vincent, A., Atkinson, J. B., Hill, M. F., Cates, J., Davidson, J. M., Rottman, J. N., Lee, E. N., & Young, P. P. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0803437105 · Cited by 174 · see citing works
Laughlin, R. C., & Temesvari, L. A. (2005) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399405009622 · Cited by 149 · see citing works
The genetic epidemiology of human primary osteoarthritis: current status
Loughlin, J. A. (2005) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399405009257 · Cited by 140 · see citing works
Frizzled‐related protein variants are risk factors for hip osteoarthritis
Lane, N. E., Lian, K., Nevitt, M. C., Zmuda, J. M., Lui, L., Li, J., Wang, J., Fontecha, M., Umblas, N., Rosenbach, M., et al. (2006) · Arthritis & Rheumatism · doi:10.1002/art.21673 · Cited by 130 · see citing works
Association of the frizzled‐related protein gene with symptomatic osteoarthritis at multiple sites
Min, J. L., Meulenbelt, I., Riyazi, N., et al. (2005) · Arthritis & Rheumatism · doi:10.1002/art.20993 · Cited by 126 · see citing works
Wnt11 Promotes Osteoblast Maturation and Mineralization through R-spondin 2
Friedman, M. S., Oyserman, S. M., & Hankenson, K. D. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808337200 · Cited by 124 · see citing works
Repair of goat tibial defects with bone marrow stromal cells and β-tricalcium phosphate
Liu, G., Zhao, L., Zhang, W., Cui, L., Liu, W. X., & Cao, Y. (2007) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-007-3348-3 · Cited by 123 · see citing works
Is osteoarthritis a heterogeneous disease that can be stratified into subsets?
Driban, J. B., Sitler, M. R., Barbe, M. F., & Balasubramanian, E. (2009) · Clinical Rheumatology · doi:10.1007/s10067-009-1301-1 · Cited by 119 · see citing works
T-cell signalling and immune system disorders
Wilkinson, B., Downey, J. S., & Rudd, C. E. (2005) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399405010264 · Cited by 100 · see citing works
Sperber, S. M., & Dawid, I. B. (2008) · Developmental Biology · doi:10.1016/j.ydbio.2008.06.004 · Cited by 89 · see citing works
Pachner, A. R., Narayan, K., Price, N., et al. (2003) · Molecular Diagnosis · doi:10.1007/bf03260016 · Cited by 89 · see citing works
Dieppe, P. A. (1999) · Osteoarthritis and Cartilage · doi:10.1053/joca.1998.0182 · Cited by 87 · see citing works
Osteoarthritis: a problem of growth not decay?
Aspden, R. M. (2008) · Lara D. Veeken · doi:10.1093/rheumatology/ken199 · Cited by 87 · see citing works
Mutations ofCOL10A1 in Schmid metaphyseal chondrodysplasia
Bateman, J. F., Wilson, R., Freddi, S., Lamandé, S. R., & Savarirayan, R. (2005) · Human Mutation · doi:10.1002/humu.20183 · Cited by 79 · see citing works
The genetic epidemiology of osteoarthritis
Valdes, A. M., & Spector, T. D. (2010) · Current Opinion in Rheumatology · doi:10.1097/bor.0b013e3283367a6e · Cited by 66 · see citing works
Runx3/AML2/Cbfa3 Regulates Early and Late Chondrocyte Differentiation
Soung, D. Y., Dong, Y., Wang, Y. J., et al. (2007) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.070502 · Cited by 64 · see citing works
Role of Runx Proteins in Chondrogenesis
Yoshida, C. A., & Komori, T. (2005) · Critical Reviews in Eukaryotic Gene Expression · doi:10.1615/critreveukargeneexpr.v15.i3.60 · Cited by 62 · see citing works
Skeletal dysplasias caused by a disruption of skeletal patterning and endochondral ossification
Newman, W. G., & Wallis, G. A. (2003) · Clinical Genetics · doi:10.1034/j.1399-0004.2003.00046.x · Cited by 40 · see citing works
Frodo proteins: modulators of Wnt signaling in vertebrate development
Brott, B. K., & Sokol, S. Y. (2005) · Differentiation · doi:10.1111/j.1432-0436.2005.00032.x · Cited by 35 · see citing works
Rollín, R., Álvarez‐Lafuente, R., Marco, F., et al. (2007) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2006.11.007 · Cited by 30 · see citing works
Self-citationRUNX3 regulates the activity of the CD11a and CD49d integrin gene promoters
Domínguez‐Soto, Á., Relloso, M., Vega, M. A., Corbí, A. L., & Puig‐Kröger, A. (2005) · Immunobiology · doi:10.1016/j.imbio.2005.05.008 · Cited by 24 · see citing works
New developments in the search for genetic determinants of osteoarthritis
Ralston, S. H. (2006) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2006.10.011 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Genetic epidemiology of hip and knee osteoarthritis
Valdes, A. M., & Spector, T. D. (2011) · Nature Reviews Rheumatology · doi:10.1038/nrrheum.2010.191 · Cited by 256 · see citing works
Yu, Y., Bhangale, T. R., Fagerness, J., Ripke, S., Thorleifsson, G., Tan, P. L., Souied, E. H., Richardson, A. J., Merriam, J. E., Buitendijk, G. H. S., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr270 · Cited by 254 · see citing works
“In patients with osteoarthritis, expression of COL10A1 was significantly downregulated (28).”
Background
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review