Limited roles of Piezo mechanosensing channels in articular cartilage development and osteoarthritis progression.
Limited roles of Piezo mechanosensing channels in articular cartilage development and osteoarthritis progression.
复制标题
压电机械传感通道在关节软骨发育和骨关节炎进展中的作用有限。
DOI：
10.1016/j.joca.2023.01.576
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发表时间：
2023
影响因子：
7
通讯作者：
Kobayashi,T
中科院分区：
文献类型：
--
作者：
Young,C;Kobayashi,T
目的研究Piezo 1和Piezo 2在手术诱导的小鼠骨关节炎（OA）中的作用。在24周龄时对OA的严重程度进行组织学评估。通过静态负重分析评价OA相关疼痛。此外，从cKO小鼠分离的关节软骨细胞暴露于流体流动剪切应力（FFSS），以评估OA相关基因的表达。ResultsPiezo 1和Piezo 2的条件性缺失的小鼠表现出正常的关节发育，在12周和24周的膝关节没有明显的组织学变化。DMM手术在对照组和cKO小鼠中均诱导了中度至重度OA（中位OARSI评分：对照组，4.67; cKO组，4.23，P = 0.3082），尽管少数cKO小鼠表现出轻度OA。通过静态负重分析进行的疼痛评估表明，关节中的压电消融对疼痛没有有益影响。结论Piezo 1和Piezo 2在正常关节发育中不是必需的。基因消融的压电通道并没有赋予明显的保护作用，对OA的进展在mice.In体外数据表明，不同的mechanictransducers以外的压电通道介导FFSS在机械应力诱导的基因表达。
ObjectiveTo investigate the role of Piezo1 and Piezo2 in surgically induced osteoarthritis (OA) in mice.DesignMale conditional knockout (cKO) mice missingPiezo1andPiezo2in the joint usingGdf5-Cretransgenic mice were induced with post-traumatic OA by destabilization of the medial meniscus (DMM) of the right knee joint at 12 weeks of age. The severity of OA was histologically assessed at 24 weeks of age. OA-associated pain was evaluated by static weight bearing analysis. Additionally, articular chondrocytes isolated from cKO mice were exposed to fluid flow shear stress (FFSS) to evaluate the expression of OA-associated genes.ResultsMice with conditional deletion ofPiezo1andPiezo2showed normal joint development with no overt histological changes in the knee joint at 12 weeks and 24 weeks. DMM surgery induced moderate to severe OA in both control and cKO mice (median OARSI score: control, 4.67; cKO, 4.23,P= 0.3082), although a few cKO mice showed milder OA. Pain assessment by static weight-bearing analysis suggested Piezo ablation in the joint has no beneficial effects on pain. FFSS increased the expression of OA-related genes both in control and cKO mice to similar extents.ConclusionPiezo1 and Piezo2 are not essential for normal joint development. Genetic ablation of Piezo channels did not confer evident protective effects on OA progression in mice.In vitro data suggests that different mechanotransducers other than Piezo channels mediate FFSS in mechanical stress-induced gene expression.