Universität zu Köln

de Kroon, Laurie M. G., van den Akker, Guus G. H., Brachvogel, Bent, Narcisi, Roberto, Belluoccio, Daniele, Jenner, Florien ORCID: 0000-0002-6977-1984, Bateman, John F., Little, Christopher B., Brama, Pieter A. J., Davidson, Esmeralda N. Blaney, van der Kraan, Peter M. and van Osch, Gerjo J. V. M. (2018). Identification of TGF beta-related genes regulated in murine osteoarthritis and chondrocyte hypertrophy by comparison of multiple microarray datasets. Bone, 116. S. 67 - 78. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1873-2763

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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 beta (TGF beta) 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 TGF beta-related genes are regulated during murine OA and endochondral ossification. Methods: A list of 580 TGF beta-related genes, including TGF beta signaling pathway components and TGF beta-target genes, was generated. Regulation of these TGF beta-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 TGF beta-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 TGF beta-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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code de Kroon, Laurie M. G. UNSPECIFIED UNSPECIFIED UNSPECIFIED van den Akker, Guus G. H. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brachvogel, Bent UNSPECIFIED UNSPECIFIED UNSPECIFIED Narcisi, Roberto UNSPECIFIED UNSPECIFIED UNSPECIFIED Belluoccio, Daniele UNSPECIFIED UNSPECIFIED UNSPECIFIED Jenner, Florien UNSPECIFIED orcid.org/0000-0002-6977-1984 UNSPECIFIED Bateman, John F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Little, Christopher B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brama, Pieter A. J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Davidson, Esmeralda N. Blaney UNSPECIFIED UNSPECIFIED UNSPECIFIED van der Kraan, Peter M. UNSPECIFIED UNSPECIFIED UNSPECIFIED van Osch, Gerjo J. V. M. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-168526
DOI:	10.1016/j.bone.2018.07.008
Journal or Publication Title:	Bone
Volume:	116
Page Range:	S. 67 - 78
Date:	2018
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1873-2763
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BONE-MINERAL DENSITY; GROWTH-FACTOR; ARTICULAR-CARTILAGE; INDIAN HEDGEHOG; TARGETED DISRUPTION; MMP-13 EXPRESSION; POTENTIAL ROLE; MESSENGER-RNA; COUP-TFII; SMAD3 Multiple languages Endocrinology & Metabolism Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/16852