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Identification of TGFβ-related genes regulated in murine osteoarthritis and chondrocyte hypertrophy by comparison of multiple microarray datasets.
Bone. 2018 11; 116:67-77.BONE

Abstract

OBJECTIVE

Osteoarthritis (OA) is a joint disease characterized by progressive degeneration of articular cartilage. Some features of OA, including chondrocyte hypertrophy and focal calcification of articular cartilage, resemble the endochondral ossification processes. Alterations in transforming growth factor β (TGFβ) signaling have been associated with OA as well as with chondrocyte hypertrophy. Our aim was to identify novel candidate genes implicated in chondrocyte hypertrophy during OA pathogenesis by determining which TGFβ-related genes are regulated during murine OA and endochondral ossification.

METHODS

A list of 580 TGFβ-related genes, including TGFβ signaling pathway components and TGFβ-target genes, was generated. Regulation of these TGFβ-related genes was assessed in a microarray of murine OA cartilage: 1, 2 and 6 weeks after destabilization of the medial meniscus (DMM). Subsequently, genes regulated in the DMM model were studied in two independent murine microarray datasets on endochondral ossification: the growth plate and transient embryonic cartilage (joint development).

RESULTS

A total of 106 TGFβ-related genes were differentially expressed in articular cartilage of DMM-operated mice compared to sham-control. From these genes, 43 were similarly regulated during chondrocyte hypertrophy in the growth plate or embryonic joint development. Among these 43 genes, 18 genes have already been associated with OA. The remaining 25 genes were considered as novel candidate genes involved in OA pathogenesis and endochondral ossification. In supplementary data of published human OA microarrays we found indications that 15 of the 25 novel genes are indeed regulated in articular cartilage of human OA patients.

CONCLUSION

By focusing on TGFβ-related genes during OA and chondrocyte hypertrophy in mice, we identified 18 known and 25 new candidate genes potentially implicated in phenotypical changes in chondrocytes leading to OA. We propose that 15 of these candidates warrant further investigation as therapeutic target for OA as they are also regulated in articular cartilage of OA patients.

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Publisher Full Text (DOI)

Authors+Show Affiliations

de Kroon LMG
Department of Rheumatology, Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands; Department of Orthopedics, Erasmus MC University Medical Center, Rotterdam, the Netherlands. Electronic address: Laurie.deKroon@radboudumc.nl.
van den Akker GGH
Department of Rheumatology, Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: Guus.vandenAkker@radboudumc.nl.
Brachvogel B
Center for Biochemistry, Medical Faculty, University of Cologne, Cologne, Germany; Department of Pediatrics and Adolescent Medicine, Experimental Neonatology, Medical Faculty, University of Cologne, Cologne, Germany. Electronic address: bent.brachvogel@uk-koeln.de.
Narcisi R
Department of Orthopedics, Erasmus MC University Medical Center, Rotterdam, the Netherlands. Electronic address: r.narcisi@erasmusmc.nl.
Belluoccio D
Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia. Electronic address: daniele_belluoccio@agilent.com.
Jenner F
Equine University Hospital, University of Veterinary Medicine, Vienna, Austria. Electronic address: florien.jenner@vetmeduni.ac.at.
Bateman JF
Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia. Electronic address: john.bateman@mcri.edu.au.
Little CB
Raymond Purves Bone and Joint Research Laboratories, Kolling Institute of Medical Research, University of Sydney, St Leonards, New South Wales, Australia. Electronic address: christopher.little@sydney.edu.au.
Brama PAJ
Veterinary Clinical Sciences, School of Veterinary Medicine, University College Dublin, Dublin, Ireland. Electronic address: pieter.brama@ucd.ie.
Blaney Davidson EN
Department of Rheumatology, Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: Esmeralda.BlaneyDavidson@radboudumc.nl.
van der Kraan PM
Department of Rheumatology, Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: Peter.vanderKraan@radboudumc.nl.
van Osch GJVM
Department of Orthopedics, Erasmus MC University Medical Center, Rotterdam, the Netherlands; Department of Otorhinolaryngology, Erasmus MC University Medical Center, Rotterdam, the Netherlands. Electronic address: g.vanosch@erasmusmc.nl.

MeSH

AnimalsCell LineChondrocytesDatabases, GeneticDisease Models, AnimalGene Expression RegulationHypertrophyJointsMaleMice, Inbred C57BLOligonucleotide Array Sequence AnalysisOsteoarthritisReproducibility of ResultsTransforming Growth Factor beta

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30010080

Citation

de Kroon, Laurie M G., et al. "Identification of TGFβ-related Genes Regulated in Murine Osteoarthritis and Chondrocyte Hypertrophy By Comparison of Multiple Microarray Datasets." Bone, vol. 116, 2018, pp. 67-77.
de Kroon LMG, van den Akker GGH, Brachvogel B, et al. Identification of TGFβ-related genes regulated in murine osteoarthritis and chondrocyte hypertrophy by comparison of multiple microarray datasets. Bone. 2018;116:67-77.
de Kroon, L. M. G., van den Akker, G. G. H., Brachvogel, B., Narcisi, R., Belluoccio, D., Jenner, F., Bateman, J. F., Little, C. B., Brama, P. A. J., Blaney Davidson, E. N., van der Kraan, P. M., & van Osch, G. J. V. M. (2018). Identification of TGFβ-related genes regulated in murine osteoarthritis and chondrocyte hypertrophy by comparison of multiple microarray datasets. Bone, 116, 67-77. https://doi.org/10.1016/j.bone.2018.07.008
de Kroon LMG, et al. Identification of TGFβ-related Genes Regulated in Murine Osteoarthritis and Chondrocyte Hypertrophy By Comparison of Multiple Microarray Datasets. Bone. 2018;116:67-77. PubMed PMID: 30010080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of TGFβ-related genes regulated in murine osteoarthritis and chondrocyte hypertrophy by comparison of multiple microarray datasets. AU - de Kroon,Laurie M G, AU - van den Akker,Guus G H, AU - Brachvogel,Bent, AU - Narcisi,Roberto, AU - Belluoccio,Daniele, AU - Jenner,Florien, AU - Bateman,John F, AU - Little,Christopher B, AU - Brama,Pieter A J, AU - Blaney Davidson,Esmeralda N, AU - van der Kraan,Peter M, AU - van Osch,Gerjo J V M, Y1 - 2018/07/21/ PY - 2017/09/07/received PY - 2018/07/10/revised PY - 2018/07/11/accepted PY - 2018/7/17/pubmed PY - 2019/7/17/medline PY - 2018/7/17/entrez KW - Chondrocyte hypertrophy KW - Microarray KW - Osteoarthritis KW - TGFβ SP - 67 EP - 77 JF - Bone JO - Bone VL - 116 N2 - OBJECTIVE: Osteoarthritis (OA) is a joint disease characterized by progressive degeneration of articular cartilage. Some features of OA, including chondrocyte hypertrophy and focal calcification of articular cartilage, resemble the endochondral ossification processes. Alterations in transforming growth factor β (TGFβ) signaling have been associated with OA as well as with chondrocyte hypertrophy. Our aim was to identify novel candidate genes implicated in chondrocyte hypertrophy during OA pathogenesis by determining which TGFβ-related genes are regulated during murine OA and endochondral ossification. METHODS: A list of 580 TGFβ-related genes, including TGFβ signaling pathway components and TGFβ-target genes, was generated. Regulation of these TGFβ-related genes was assessed in a microarray of murine OA cartilage: 1, 2 and 6 weeks after destabilization of the medial meniscus (DMM). Subsequently, genes regulated in the DMM model were studied in two independent murine microarray datasets on endochondral ossification: the growth plate and transient embryonic cartilage (joint development). RESULTS: A total of 106 TGFβ-related genes were differentially expressed in articular cartilage of DMM-operated mice compared to sham-control. From these genes, 43 were similarly regulated during chondrocyte hypertrophy in the growth plate or embryonic joint development. Among these 43 genes, 18 genes have already been associated with OA. The remaining 25 genes were considered as novel candidate genes involved in OA pathogenesis and endochondral ossification. In supplementary data of published human OA microarrays we found indications that 15 of the 25 novel genes are indeed regulated in articular cartilage of human OA patients. CONCLUSION: By focusing on TGFβ-related genes during OA and chondrocyte hypertrophy in mice, we identified 18 known and 25 new candidate genes potentially implicated in phenotypical changes in chondrocytes leading to OA. We propose that 15 of these candidates warrant further investigation as therapeutic target for OA as they are also regulated in articular cartilage of OA patients. SN - 1873-2763 UR - https://www.unboundmedicine.com/medline/citation/30010080/Identification_of_TGF��_related_genes_regulated_in_murine_osteoarthritis_and_chondrocyte_hypertrophy_by_comparison_of_multiple_microarray_datasets_ DB - PRIME DP - Unbound Medicine ER -