ArticleArthritis and rheumatism2008
Differential expression of GADD45beta in normal and osteoarthritic cartilage: potential role in homeostasis of articular chondrocytes.
Article in Arthritis and rheumatism, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 99 citations in OpenAlex.
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- The Role of Regulated Programmed Cell Death in Osteoarthritis: From Pathogenesis to Therapy.International journal of molecular sciences · 2023Review
- Disease modification and symptom relief in osteoarthritis using a mutated GCP-2/CXCL6 chemokine.EMBO molecular medicine · 2023Article
- Mutation in the CCAL1 locus accounts for bidirectional process of human subchondral bone turnover and cartilage mineralization.Rheumatology (Oxford, England) · 2022Article
- Inhibiting thyroid activation in aged human explants prevents mechanical induced detrimental signalling by mitigating metabolic processes.Rheumatology (Oxford, England) · 2022Article
- Mass spectrometry-based proteomics identify novel serum osteoarthritis biomarkers.Arthritis research & therapy · 2022Article
- The essential anti-angiogenic strategies in cartilage engineering and osteoarthritic cartilage repair.Cellular and molecular life sciences : CMLS · 2022Review
- Unbiased transcriptome mapping and modeling identify candidate genes and compounds of osteoarthritis.Frontiers in pharmacology · 2022Article
- Basal and IL-1β enhanced chondrocyte chemotactic activity on monocytes are co-dependent on both IKKα and IKKβ NF-κB activating kinases.Scientific reports · 2021Article
- The role of microRNA-3085 in chondrocyte function.Scientific reports · 2020Article
- A Microarray Study of Articular Cartilage in Relation to Obesity and Severity of Knee Osteoarthritis.Cartilage · 2020Article
- Integration of transcriptome-wide association study and messenger RNA expression profile to identify genes associated with osteoarthritis.Bone & joint research · 2020Article
- Review
- Global transcriptome analysis to identify critical genes involved in the pathology of osteoarthritis.Bone & joint research · 2018Article
- Recent Insights into the Contribution of the Changing Hypertrophic Chondrocyte Phenotype in the Development and Progression of Osteoarthritis.Frontiers in bioengineering and biotechnology · 2018Review
- Quantitative proteomics analysis of cartilage response to mechanical injury and cytokine treatment.Matrix biology : journal of the International Society for Matrix Biology · 2017Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
Abstract
objectiveOur previous study suggested that growth arrest and DNA damage-inducible protein 45beta (GADD45beta) prolonged the survival of hypertrophic chondrocytes in the developing mouse embryo. This study was undertaken, therefore, to investigate whether GADD45beta plays a role in adult articular cartilage.
methodsGene expression profiles of cartilage from patients with late-stage osteoarthritis (OA) were compared with those from patients with early OA and normal controls in 2 separate microarray analyses. Histologic features of cartilage were graded using the Mankin scale, and GADD45beta was localized by immunohistochemistry. Human chondrocytes were transduced with small interfering RNA (siRNA)-GADD45beta or GADD45beta-FLAG. GADD45beta and COL2A1 messenger RNA (mRNA) levels were analyzed by real-time reverse transcriptase-polymerase chain reaction, and promoter activities were analyzed by transient transfection. Cell death was detected by Hoechst 33342 staining of condensed chromatin.
resultsGADD45beta was expressed at higher levels in cartilage from normal donors and patients with early OA than in cartilage from patients with late-stage OA. All chondrocyte nuclei in normal cartilage immunostained for GADD45beta. In early OA cartilage, GADD45beta was distributed variably in chondrocyte clusters, in middle and deep zone cells, and in osteophytes. In contrast, COL2A1, other collagen genes, and factors associated with skeletal development were up-regulated in late OA, compared with early OA or normal cartilage. In overexpression and knockdown experiments, GADD45beta down-regulated COL2A1 mRNA and promoter activity. NF-kappaB overexpression increased GADD45beta promoter activity, and siRNA-GADD45beta decreased cell survival per se and enhanced tumor necrosis factor alpha-induced cell death in human articular chondrocytes.
conclusionThese observations suggest that GADD45beta might play an important role in regulating chondrocyte homeostasis by modulating collagen gene expression and promoting cell survival in normal adult cartilage and in early OA.
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