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ZBTB16 eases lipopolysaccharide‑elicited inflammation, apoptosis and degradation of extracellular matrix in chondrocytes during osteoarthritis by suppressing GRK2 transcription

  • Authors:
    • Bo Xiong
    • Lihua Chen
    • Yue Huang
    • Guanyu Lu
    • Cai Chen
    • Jiao Nong
    • Haida Pan
  • View Affiliations / Copyright

    Affiliations: Department of Orthopaedics and Traumatology, First Affiliated Hospital of The Guangxi University of Chinese Medicine, Nanning, Guangxi 530000, P.R. China, Teaching Department, First Affiliated Hospital of The Guangxi University of Chinese Medicine, Nanning, Guangxi 530000, P.R. China, Department of Orthopaedics and Traumatology, Yongjia County Traditional Chinese Medicine Hospital, Wenzhou, Zhejiang 325100, P.R. China
    Copyright: © Xiong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 276
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    Published online on: April 24, 2023
       https://doi.org/10.3892/etm.2023.11975
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Abstract

Osteoarthritis (OA) is a chronic degenerative disease of the bone that is a major contributor of disability in the elderly population. Zinc finger and BTB domain‑containing 16 (ZBTB16) is a transcription factor that has been previously revealed to be impaired in human OA tissues. The present study was designed to elaborate the potential impact of ZBTB16 on OA and to possibly assess any latent regulatory mechanism. ZBTB16 expression in human OA tissues was examined using the Gene Expression Series (GSE) database (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE169077) whereas ZBTB16 expression in chondrocytes was examined using reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting. Cell viability was examined using a Cell Counting Kit‑8 assay. A TUNEL assay and western blotting were used to assess cell apoptosis and apoptosis‑related markers, including Bcl‑2, Bax and cleaved caspase‑3. The levels and expression of inflammatory factors, including TNF‑α, IL‑1β and IL‑6, were determined by ELISA and western blotting. RT‑qPCR and western blotting were also used to analyze the expression levels of extracellular matrix (ECM)‑degrading enzymes, including MMP‑13, a disintegrin‑like and metalloproteinase with thrombospondin type‑1 motifs‑5, aggrecan and collagen type II α1. After the potential binding of ZBTB16 with the G protein coupled receptor kinase type 2 (GRK2) promoter was predicted using the Cistrome DB database, GRK2 expression was confirmed by RT‑qPCR and western blotting. Chromatin immunoprecipitation and luciferase reporter assays were then used to determine the potential interaction between ZBTB16 and the GRK2 promoter. Following GRK2 overexpression in ZBTB16‑overexpressing chondrocytes by co‑transfection of GRK2 and ZBTB16 overexpression plasmids, the aforementioned functional experiments were performed again. ZBTB16 expression was found to be reduced in human OA tissues compared with in normal cartilage tissues and lipopolysaccharide (LPS)‑stimulated chondrocytes. ZBTB16 overexpression increased cell viability whilst decreasing apoptosis, inflammation and ECM degradation by LPS‑treated chondrocytes. In addition, GRK2 expression was found to be increased in LPS‑stimulated chondrocytes. ZBTB16 successfully bound to the GRK2 promoter, which negatively modulated GRK2 expression. GRK2 upregulation reversed the effects of ZBTB16 overexpression on the viability, apoptosis, inflammation and ECM degradation by LPS‑challenged chondrocytes. In conclusion, these data suggest that ZBTB16 may inhibit the development of OA through the transcriptional inactivation of GRK2.
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Copy and paste a formatted citation
Spandidos Publications style
Xiong B, Chen L, Huang Y, Lu G, Chen C, Nong J and Pan H: ZBTB16 eases lipopolysaccharide‑elicited inflammation, apoptosis and degradation of extracellular matrix in chondrocytes during osteoarthritis by suppressing GRK2 transcription. Exp Ther Med 25: 276, 2023.
APA
Xiong, B., Chen, L., Huang, Y., Lu, G., Chen, C., Nong, J., & Pan, H. (2023). ZBTB16 eases lipopolysaccharide‑elicited inflammation, apoptosis and degradation of extracellular matrix in chondrocytes during osteoarthritis by suppressing GRK2 transcription. Experimental and Therapeutic Medicine, 25, 276. https://doi.org/10.3892/etm.2023.11975
MLA
Xiong, B., Chen, L., Huang, Y., Lu, G., Chen, C., Nong, J., Pan, H."ZBTB16 eases lipopolysaccharide‑elicited inflammation, apoptosis and degradation of extracellular matrix in chondrocytes during osteoarthritis by suppressing GRK2 transcription". Experimental and Therapeutic Medicine 25.6 (2023): 276.
Chicago
Xiong, B., Chen, L., Huang, Y., Lu, G., Chen, C., Nong, J., Pan, H."ZBTB16 eases lipopolysaccharide‑elicited inflammation, apoptosis and degradation of extracellular matrix in chondrocytes during osteoarthritis by suppressing GRK2 transcription". Experimental and Therapeutic Medicine 25, no. 6 (2023): 276. https://doi.org/10.3892/etm.2023.11975
Copy and paste a formatted citation
x
Spandidos Publications style
Xiong B, Chen L, Huang Y, Lu G, Chen C, Nong J and Pan H: ZBTB16 eases lipopolysaccharide‑elicited inflammation, apoptosis and degradation of extracellular matrix in chondrocytes during osteoarthritis by suppressing GRK2 transcription. Exp Ther Med 25: 276, 2023.
APA
Xiong, B., Chen, L., Huang, Y., Lu, G., Chen, C., Nong, J., & Pan, H. (2023). ZBTB16 eases lipopolysaccharide‑elicited inflammation, apoptosis and degradation of extracellular matrix in chondrocytes during osteoarthritis by suppressing GRK2 transcription. Experimental and Therapeutic Medicine, 25, 276. https://doi.org/10.3892/etm.2023.11975
MLA
Xiong, B., Chen, L., Huang, Y., Lu, G., Chen, C., Nong, J., Pan, H."ZBTB16 eases lipopolysaccharide‑elicited inflammation, apoptosis and degradation of extracellular matrix in chondrocytes during osteoarthritis by suppressing GRK2 transcription". Experimental and Therapeutic Medicine 25.6 (2023): 276.
Chicago
Xiong, B., Chen, L., Huang, Y., Lu, G., Chen, C., Nong, J., Pan, H."ZBTB16 eases lipopolysaccharide‑elicited inflammation, apoptosis and degradation of extracellular matrix in chondrocytes during osteoarthritis by suppressing GRK2 transcription". Experimental and Therapeutic Medicine 25, no. 6 (2023): 276. https://doi.org/10.3892/etm.2023.11975
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