Dataset Information

FGA can be used as a promising therapeutic target in osteoarthritis

ABSTRACT: Twenty-six patients who underwent knee joint surgery at the Department of Orthopedics from January 2023 to December 2023 were selected. OA knee cartilage extracted during surgery was included in the experimental group, and normal knee cartilage extracted during surgery was included in the control group. To explore the pathogenic gene of OA and verify it by experiments.

ORGANISM(S): Homo Sapiens

SUBMITTER: Guanhong Chen

PROVIDER: PXD063166 | iProX | Mon Apr 21 00:00:00 BST 2025

REPOSITORIES: iProX

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FGA can be used as a promising therapeutic target in osteoarthritis.

Chen Guanhong G Zhang Han H Bai Xizhuang X

BMC musculoskeletal disorders 20250520 1

<h4>Background</h4>This study aims to identify critical signaling pathways and pathogenic genes involved in osteoarthritis (OA) to provide a foundation for identifying targeted therapeutic strategies.<h4>Methods</h4>Twenty-six patients who underwent knee joint surgery in the Department of Orthopedics between January and December 2023 were enrolled. Cartilage samples in the experimental group (OA group) were harvested from the articular surfaces of the knee joints of OA patients undergoing total ...[more]

PMID: 40394574

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Project description:Mechanical Stimuli are arguably the most important aetiolgical factors in osteoarthritis (OA) development. Not only do we see disease arising from joints where the cartilage has sustained direct (e.g. intraarticular fracture) or indirect (e.g. meniscal injury) trauma, but mechanical factors are considered, at least partly, to explain the disease associations with aging and obesity. It is now well established that OA is not simply due to repeated wear and tear, leading to attrition of the articular surfaces, but that it requires activation of a number of inflammatory genes, which drive catabolic protease activity in the joint. These enzymes lead to breakdown of the major extracellular matrix components of cartilage, namely type II collagen, and the proteoglycan, aggrecan. Although it is unclear precisely which enzymes are responsible for matrix breakdown in human OA, Glasson et al showed that deletion of the aggrecan degrading enzyme, ADAMTS5 substantially protected the joint from surgically induced murine OA suggesting that it is a major aggrecanase in the mouse. This study was part of a wider study using the surgical model of murine OA, induced by destabilising the medial meniscus (DMM), to confirm the dependence of joint loading on disease progression and to reveal mechanosensitive genes within the joint which may be involved in the development of OA. Using this model we, and others, have shown that there is a robust degradation of articular cartilage over 4-12wks in male C57B/6 mice. We identified the gene response in joints early following induction of OA, prior to cartilage degradation, by extracting RNA from whole joints (after skin and muscle had been removed) 6hrs, 3 days and 7 days following sham and DMM surgery. An Affymetrix ST1 gene array was performed. Significantly regulated genes (>1.4 fold above naive and sham samples at any timepoint), or those considered to have a putative role in OA pathogenesis were selected for quantitative validation using Taqman low density microfluidic card arrays (TLDA). Gene expression in whole knee joints at 3 early time points post DMM surgery (before cartilage loss), 6hrs, 3days and 7days was examined. Two controls were identified, the first control consisted of age matched naïve mice that had undergone 15 minutes of anaesthesia but were not operated on (0hrs post surgery). The second control included mice which had undergone sham surgery (capsulotomy alone). For this RNA was taken at the same time points post surgery as DMM samples (6hrs, 3days and 7days). There were three biological replicates per condition (total of 21 samples). The right (ipsilateral) knee joint was taken and RNA extracted and processed for microarray analysis using the Affymetrix Mouse Gene 1.0 st v1 platform.

Dataset Information

FGA can be used as a promising therapeutic target in osteoarthritis

Publications

FGA can be used as a promising therapeutic target in osteoarthritis.

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