Influence of osteoarthritis grade on molecular signature of human cartilage

Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society
Shuanhu ZhouJulie Glowacki

Abstract

Articular chondrocytes maintain cartilage matrix turnover and have the capacity for anabolic and catabolic activities that can be influenced by injury and disease. This study tested the hypothesis that catabolic genes are upregulated with regional osteoarthritis (OA) disease severity within a joint. With IRB approval, specimens of knee cartilage obtained as discarded tissues from subjects undergoing arthroplasty were partitioned for each subject by OA disease severity and evaluated for gene expression by RT-PCR. There was regional OA grade-associated upregulation of expected inflammatory mediators TNF-α, TNF receptors, IFN-γ, and interleukins as well as genes encoding proteolytic enzymes, including Adamts-5 and MMPs. Osteoclast-related genes, cathepsin K, tartrate-resistant acid phosphatase (TRAP), RANKL, RANK, M-CSF, and c-fms, but not osteoprotegerin, were induced in advanced grades. In vitro treatment of normal human chondrocytes with interleukin-1β upregulated similar genes; this provides evidence that chondrocytes per se can be the source of osteoclast-related factors. Immunohistochemical staining showed that RANK- and RANKL-positive cells were abundant in advanced grades, especially in chondrocyte clusters. This suggests ...Continue Reading

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Citations

Sep 28, 2016·Bone Research·David M Findlay, Julia S Kuliwaba
Oct 21, 2016·Nature Reviews. Rheumatology·Steven R Goldring, Mary B Goldring
Feb 9, 2017·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Xiao-Feng WuJian Zou
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Dec 17, 2020·Frontiers in Cell and Developmental Biology·Sina StuckerAnjali P Kusumbe
Jul 21, 2021·Seminars in Cell & Developmental Biology·Charlotte Owen-Woods, Anjali Kusumbe

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