The role of cytokine receptor-like factor 1 (CRLF1) in facet joint osteoarthritis pathogenesis.

Autor: Xue P; Department of orthopaedics, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226001, China; Medical School of Southeast University, Nanjing, Jiangsu 210009, China., Jin H; Department of orthopaedics, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226001, China., Zhou X; Department of orthopaedics, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226001, China., Cui Z; Department of orthopaedics, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226001, China., Cui D; Department of orthopaedics, Affiliated Hospital 2 of Nantong University, Nantong, Jiangsu 226001, China. Electronic address: cuidaoran2024@163.com.
Jazyk: angličtina
Zdroj: Experimental gerontology [Exp Gerontol] 2024 Oct 01; Vol. 195, pp. 112543. Date of Electronic Publication: 2024 Aug 12.
DOI: 10.1016/j.exger.2024.112543
Abstrakt: Background: Facet joint osteoarthritis (FJOA) is a prevalent condition contributing to low back pain, particularly in the elderly population. This study aimed to investigate the potential role of Cytokine Receptor-like Factor 1 (CRLF1) in FJOA pathogenesis and its therapeutic implications.
Methods: Bioinformatics analysis was utilized to identify CRLF1 as the target gene, followed by quantification of CRLF1 expression levels and joint degeneration degree using immunohistochemistry (IHC). In primary chondrocytes, the inhibition of CRLF1 expression by siRNA was performed, and Western blot analysis was conducted to evaluate the involvement of the extracellular matrix and MAPK/ERK signaling pathway. Flow cytometry was employed to assess the apoptosis rate of chondrocytes, while immunofluorescence (IF) was utilized to evaluate the localization of CRLF1, cleaved-caspase3, MMP13, COL2A1, and ERK.
Results: The expression of CRLF1 was found to be significantly elevated in FJOA tissues compared to normal tissues. Through the use of loss-of-function assays, it was determined that CRLF1 not only enhanced the rate of apoptosis in chondrocytes, but also facilitated the degradation of the extracellular matrix in vitro. Furthermore, CRLF1 was found to activate the ERK1/2 pathways. The pro-arthritic effects elicited by CRLF1 were mitigated by treatment with the MEK inhibitor U0126 in chondrocytes.
Conclusion: These results suggest that CRLF1 enhances chondrocytes apoptosis and extracellular matrix degration in FJOA and thus may therefore be a potential therapeutic target for FJOA.
Competing Interests: Declaration of competing interest All the authors listed assure that the data in the manuscript is original and the manuscript is not under consideration elsewhere. None of the manuscript contents have been previously published. All authors have made significant contributions of this work, and have read and approved all versions of the manuscript, its content, and its submission to the journal. The authors have no conflict of interests.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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