Low fluid shear stress promotes chondrocyte proliferation and extracellular matrix secretion by downregulating mir-143-3p and activating the ERK5/KLF4 signaling pathway

Autor: Jun Zhao, Yayi Xia, Jinwen He
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Scientific Reports, Vol 14, Iss 1, Pp 1-13 (2024)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-024-78676-w
Popis: Abstract Low fluid shear stress (FSS, ≤ 2 dyn/cm2) has been shown to exert protective effects on chondrocytes, but the underlying molecular mechanisms remain unclear. This study aimed to elucidate the mechanisms by which FSS promotes chondrocyte proliferation and extracellular matrix (ECM) stability. We exposed SW1353 chondrocytes to low FSS (1.8 dyn/cm2, 60 min) and found that it led to a significant downregulation of microRNA-143-3p (miR-143-3p), which was associated with increased chondrocyte proliferation and ECM secretion, including type II collagen (COL2A1) and aggrecan. Further investigation revealed that miR-143-3p directly targeted ERK5, a key component of the ERK5/KLF4 signaling pathway. Overexpression of miR-143-3p suppressed ERK5/KLF4 pathway activation, resulting in reduced chondrocyte proliferation and ECM production. Our findings demonstrate that low FSS promotes chondrocyte proliferation and ECM secretion by downregulating miR-143-3p, leading to the activation of the ERK5/KLF4 signaling pathway. This study reveals a novel mechanism by which FSS regulates chondrocyte behavior and ECM secretion, highlighting the potential of FSS as a therapeutic target for cartilage-related diseases.
Databáze: Directory of Open Access Journals
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