Department of Orthopaedics, Lanzhou University Second Hospital, #82 Cuiyingmen, Lanzhou, 730000, Gansu, China.
Orthopaedics Key Laboratory of Gansu Province, Lanzhou, Gansu, China.
Sci Rep. 2024 Nov 12;14(1):27737. doi: 10.1038/s41598-024-78676-w.
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/cm, 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.
低流体切应力（FSS，≤2 dyn/cm2）已被证明对软骨细胞具有保护作用，但其中的分子机制尚不清楚。本研究旨在阐明 FSS 促进软骨细胞增殖和细胞外基质（ECM）稳定的机制。我们将 SW1353 软骨细胞暴露于低 FSS（1.8 dyn/cm，60 分钟）下，发现其导致 microRNA-143-3p（miR-143-3p）显著下调，这与软骨细胞增殖和 ECM 分泌增加有关，包括 II 型胶原（COL2A1）和聚集蛋白聚糖。进一步的研究表明，miR-143-3p 直接靶向 ERK5，ERK5/KLF4 信号通路的关键组成部分。miR-143-3p 的过表达抑制了 ERK5/KLF4 通路的激活，导致软骨细胞增殖和 ECM 产生减少。我们的研究结果表明，低 FSS 通过下调 miR-143-3p 促进软骨细胞增殖和 ECM 分泌，从而激活 ERK5/KLF4 信号通路。本研究揭示了 FSS 调节软骨细胞行为和 ECM 分泌的新机制，强调了 FSS 作为治疗与软骨相关疾病的潜在靶点的可能性。
