Low-intensity pulsed ultrasound inhibits VEGFA expression in chondrocytes and protects against cartilage degeneration in experimental osteoarthritis
Low-intensity pulsed ultrasound inhibits VEGFA expression in chondrocytes and protects against cartilage degeneration in experimental osteoarthritis
复制标题
低强度脉冲超声抑制软骨细胞中 VEGFA 的表达并防止实验性骨关节炎中的软骨退化
DOI：
10.1002/2211-5463.12801
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发表时间：
2020-02-05
期刊：
影响因子：
2.6
通讯作者：
Bai, Dingqun
中科院分区：
文献类型：
--
作者：
Guan, Mengtong;Zhu, Ying;Bai, Dingqun
低强度脉冲超声(LIPUS)是一种非侵入性的物理疗法，近年来被证明是治疗骨关节炎(OA)的有效方法。血管内皮生长因子A(VEGFA)在骨性关节炎患者的关节软骨、滑膜和软骨下骨中表达上调，导致软骨退变、滑膜炎和骨赘形成。然而，LIPUS调节软骨细胞来源的VEGFA表达的功能和机制仍不清楚。在这项研究中，我们研究了LIPUS是否通过(A)降低内侧半月板手术引起的小鼠关节软骨中VEGFA阳性细胞的百分比，以及(B)减轻白介素1β诱导的小鼠原代软骨细胞中VEGFA的表达来减缓OA的进展。然而，这一功能被p38丝裂原活化蛋白激酶(P38 MAPK)抑制剂所否定。此外，我们发现LIPUS改善了VEGFA介导的软骨细胞外基质代谢紊乱和软骨细胞肥大。综上所述，我们的数据表明LIPUS通过抑制p38 MAPK活性来调节骨关节炎软骨细胞来源的VEGFA的表达。
Low-intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, was recently demonstrated to be an effective treatment for osteoarthritis (OA). Vascular endothelium growth factor A (VEGFA) has been found to be upregulated in the articular cartilage, synovium and subchondral bone of OA patients, leading to cartilage degeneration, synovitis and osteophyte formation. However, the functions and mechanisms of LIPUS in regulating chondrocyte-derived VEGFA expression are still unclear. In this study, we investigated whether LIPUS attenuated OA progression by (a) decreasing the percentage of VEGFA-positive cells in mouse articular cartilage destabilised through medial meniscus surgery and (b) relieving interleukin-1 beta-induced VEGFA expression in mouse primary chondrocytes. However, this function was negated by a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor. In addition, we found that LIPUS ameliorated VEGFA-mediated disorders in cartilage extracellular matrix metabolism and chondrocyte hypertrophy during OA development. In conclusion, our data indicate a novel effect of LIPUS in regulating the expression of osteoarthritic chondrocyte-derived VEGFA through the suppression of p38 MAPK activity.