| 侯雯洁,潘春然,邓晓凤,等.低强度脉冲超声通过抑制SPHK1/NF-κB信号轴改善骨关节炎进展.骨科,2025,16(2): 134-143. |
| 低强度脉冲超声通过抑制SPHK1/NF-κB信号轴改善骨关节炎进展 |
| Low-intensity pulsed ultrasound alleviates the progression of osteoarthritis by inhibiting the SPHK1/NF-κB signaling axis |
| 投稿时间：2024-12-24 |
| DOI：10.3969/j.issn.1674-8573.2025.02.006 |
| 中文关键词: 骨关节炎 低强度脉冲超声 鞘磷脂激酶1 核因子κB |
| 英文关键词: Osteoarthritis Low-intensity pulsed ultrasound SPHK1 NF-κB |
| 基金项目:国家自然科学基金（82272610） |
|
| 摘要点击次数: 238 |
| 全文下载次数: 71 |
| 中文摘要: |
| 目的 研究特定的低强度脉冲超声（low-intensity pulsed ultrasound，LIPUS）通过调控鞘磷脂激酶1（sphingosine kinase 1，SPHK1）/核因子κB（nuclear factor-kappa B，NF-κB）通路治疗骨关节炎（osteoarthritis，OA）的机制与效果。方法 利用GEO和GeneCards数据库等生物信息学技术，筛选OA进展中的关键基因。在细胞实验中，使用白细胞介素-1β（interleukin-1 beta，IL-1β）构建炎症-退行性软骨细胞模型，检测SPHK1的表达水平。采用过表达腺病毒和siRNA干预调控SPHK1的表达，探讨SPHK1对软骨细胞代谢与功能的影响。此外，施加特定强度的LIPUS干预软骨细胞，研究其对软骨细胞功能与代谢平衡的调节作用。在动物实验中，建立SD大鼠内侧半月板不稳定（medial meniscal destabilization，DMM）模型，通过给予30 mW/cm2、20 min/天、5天/周、6周的LIPUS干预，观察LIPUS对OA进展的影响。结果 生物信息学分析确定SPHK1是OA进展中的关键基因之一。在炎症刺激下，SPHK1在软骨细胞中的表达显著上调，过表达SPHK1可破坏软骨细胞合成代谢与分解代谢的平衡，并激活NF-κB通路，增强软骨细胞的炎症反应和退变。通过siRNA敲低SPHK1和LIPUS干预，SPHK1的表达显著下调，NF-κB通路被抑制，软骨细胞功能得到保护，炎症反应减轻。LIPUS干预显著降低DMM大鼠关节软骨中SPHK1的表达，缓解软骨损伤并改善OA病理进展。结论 特定强度的LIPUS干预能通过抑制SPHK1/NF-κB通路改善OA进展。 |
| 英文摘要: |
| Objective To explore the mechanisms and therapeutic effects of specific intensity low-intensity pulsed ultrasound (LIPUS) in treating osteoarthritis (OA) by regulating the sphingosine kinase 1 (SPHK1)/nuclear factor-kappa B (NF-κB) pathway. Methods Bioinformatics tools, including GEO and GeneCards databases, were used to identify key genes involved in OA progression. In cell experiments, an interleukin-1 beta (IL-1β)-induced inflammatory-degenerative chondrocyte model was established, and the expression level of SPHK1 was assessed. Adenovirus overexpression and siRNA-mediated knockdown were employed to regulate SPHK1 expression and investigate its impact on chondrocyte metabolism and function. Additionally, LIPUS with specific intensity was applied to chondrocytes to study its effects on cell function and metabolic balance. In animal experiments, a medial meniscal destabilization (DMM) model was established in SD rats, and LIPUS was applied at 30 mW/cm2, 20 min/day, 5 days/week for 6 weeks to evaluate its effect on OA progression. Results Bioinformatics analysis identified SPHK1 as one of the key genes in OA progression. Upon inflammatory stimulation, SPHK1 expression was significantly upregulated in chondrocytes. Overexpression of SPHK1 disrupted the balance between anabolic and catabolic metabolism in chondrocytes, activated the NF-κB pathway, and exacerbated inflammatory responses and degeneration. SPHK1 knockdown via siRNA and LIPUS treatment significantly downregulated SPHK1 expression, inhibited the NF-κB pathway, and protected chondrocyte function, reducing inflammation. LIPUS intervention notably decreased SPHK1 expression in the articular cartilage of DMM rats, alleviated cartilage damage, and improved the pathological progression of OA. Conclusion Specific intensity LIPUS treatment can improve OA progression by inhibiting the SPHK1/NF-κB pathway, offering a potential therapeutic strategy for managing OA. |
|
查看全文
下载PDF阅读器 |
| 关闭 |
|
|
|
