Gene expression in human chondrocytes in late osteoarthritis is changed in both fibrillated and intact cartilage without evidence of generalised chondrocyte hypertrophy

Brew, C J; Clegg, P D; Boot-Handford, R P; Andrew, J G; Hardingham, T

doi:10.1136/ard.2008.097139

Cited by 134Osteoarthritis Treatment and MechanismsProteoglycans and glycosaminoglycans researchHip disorders and treatments

Gene expression in human chondrocytes in late osteoarthritis is changed in both fibrillated and intact cartilage without evidence of generalised chondrocyte hypertrophy

Brew, C J, Clegg, P D, Boot-Handford, R P, Andrew, J G, Hardingham, T·2010·Annals of the Rheumatic Diseases

DOI 10.1136/ard.2008.097139

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Abstract

Objectives To investigate changes in gene expression in fibrillated and intact human osteoarthritis (OA) cartilage for evidence of an altered chondrocyte phenotype and hypertrophy.Methods Paired osteochondral samples were taken from a high-load site and a low-load site from 25 OA joints and were compared with eight similar paired samples from age-matched controls. Gene expression of key matrix and regulatory genes was analysed by quantitative real-time reverse transcription-polymerase chain reaction on total RNA extracted from the cartilage.Results There was a major change in chondrocyte gene expression in OA cartilage. SOX9 (38-fold) and aggrecan (4-fold) gene expression were both lower in OA (p<0.001), and collagen I (17-fold) and II (2.5-fold) gene expression were each increased in a subset of OA samples. The major changes in gene expression were similar at the fibrillated high-loaded site and the intact low-loaded site. There was no evidence of a generalised change in OA to proliferative or hypertrophic phenotype as seen in the growth plate, as genes associated with either stage of differentiation were unchanged (PTHrPR), or significantly downregulated (collagen X (14-fold, p<0.002), VEGF (23-fold, p<0.02), BCL-2 (5.6-fold, p<0.001), matrilin-1 (6.5-fold, p<0.001)). In contrast MMP-13 was significantly upregulated in the OA cartilage samples (5.3-fold, p<0.003).Conclusions The expression of key chondrocyte genes, including aggrecan and SOX9, was decreased in OA cartilage and the changes were similar in both fibrillated high-loaded and intact low-loaded cartilage on the same joint. However, there was no significant upregulation of type X collagen, and other genes associated with chondrocyte further differentiation and hypertrophy.

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MMP-13 is predominantly expressed in lower intermediate and deep layers of cartilage in early OA, while aggrecanases are expressed in superficial cartilage.
“In the early phases of OA, MMP-13 is predominantly expressed in the lower intermediate and deep layers of human and mouse cartilage, whereas aggrecanases are expressed in the superficial cartilage [25,26].”
From Arthropod steroid hormone (20-Hydroxyecdysone) suppresses IL-1β- induced catabolic gene expression in cartilage (2015) · cites this paper as [25]

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Authors: Brew, C. J., Clegg, P. D., Boot-Handford, R. P., Andrew, J. G., & Hardingham, T.
Affiliations: Wellcome Centre for Cell-Matrix Research (GB)
University of Liverpool (GB)
Ysbyty Gwynedd Hospital NHS Trust (GB)
Corresponding author: Clegg, P D
ORCID: Clegg, P D
Boot-Handford, R P
Hardingham, T
Venue: Annals of the Rheumatic Diseases
Publisher: Elsevier BV
Published: 2010-01
Volume: 69
Issue: 1
Pages: 234-240
ISSN: 0003-4967 (ISSN-L)
DOI: 10.1136/ard.2008.097139
OpenAlex: W2160964180
Cited by: 134
References: 48
Citations by year: 2025: 4 · 2024: 5 · 2023: 5 · 2022: 4 · 2021: 12 · 2020: 3 · 2019: 10 · 2018: 6 · 2017: 7 · 2016: 10 · 2015: 8 · 2014: 11 · 2013: 7 · 2012: 16
FWCI: 5.98
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Annals of the Rheumatic Diseases (publishedVersion)
PubMed (publishedVersion)
HighWire Press Open Archive (submittedVersion)
Research Explorer (The University of Manchester) (submittedVersion)
Funders: Wellcome Trust
Biotechnology and Biological Sciences Research Council
Topics: Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
Health Sciences › Medicine › Surgery › Hip disorders and treatments
Keywords: osteoarthritis, chondrocyte gene expression, cartilage, chondrocyte hypertrophy, SOX9, aggrecan, type II collagen, type I collagen, MMP-13, type X collagen
MeSH terms: Aged, Aged, 80 and over, Cartilage, Articular, Collagen, Female, Gene Expression Regulation, Humans, Hypertrophy, Knee Joint, Male, Middle Aged, RNA, Messenger, Weight-Bearing, Chondrocytes, Osteoarthritis, Knee, Gene Expression Profiling, Aggrecans, SOX9 Transcription Factor

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Gene expression in human chondrocytes in late osteoarthritis is changed in both fibrillated and intact cartilage without evidence of generalised chondrocyte hypertrophy

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