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桡骨体外冲击波疗法可减轻膝关节骨关节炎患者的软骨下成骨细胞衰老。

Radial Extracorporeal Shockwave Therapy Reduces Subchondral Osteoblast Senescence in Knee Osteoarthritis.

作者信息

Chen Lin, Zhang Zhan, Ma Xun, Zhang Di, Xu Qi, Wang Qian, Pan Shinong, He Yu, Liu Xueyong

机构信息

Department of Rehabilitation, Shengjing Hospital of China Medical University, Shenyang, China.

Department of Orthopedics, Shengjing Hospital of China Medical University, Shenyang, China.

出版信息

Am J Sports Med. 2025 Aug;53(10):2352-2362. doi: 10.1177/03635465251355245. Epub 2025 Jul 17.

DOI:10.1177/03635465251355245
PMID:40673558
Abstract

BACKGROUND

Excess subchondral bone (SCB) turnover due to osteoblast senescence has been confirmed as the histological manifestation of early-stage osteoarthritis (OA). The therapeutic efficacy of radial extracorporeal shockwave therapy (rESWT) on osteoblast senescence in early-stage OA has not been fully elucidated.

PURPOSE

To evaluate the therapeutic potential of rESWT in enhancing SCB osteogenesis and mitigating osteoblast senescence in a rat model of knee OA.

STUDY DESIGN

Controlled laboratory study.

METHODS

The expression of senescence biomarkers was evaluated by immunohistochemistry on tibial plateau samples from patients with knee OA (n = 3). Monosodium iodoacetate (MIA)-induced OA was established in 8-week-old male Sprague-Dawley rats, which were treated with 3 different doses of rESWT (0.096, 0.128, or 0.16 mJ/mm; n = 6 per group) for 4 weeks. Articular cartilage and SCB samples were collected and analyzed using histological, radiological, immunohistochemical, and immunofluorescence techniques to assess the tissue repair, osteogenic, and antisenescence effects of rESWT as well as to identify the optimal therapeutic dose. Then, a new set of rats with MIA-induced OA that received rESWT, treadmill exercise, or combined therapy (n = 6 per group) was used to compare the therapeutic effects of the 3 methods on knee OA. For in vitro analysis, the impact of rESWT on senescence biomarkers was further evaluated using TNF-α-stimulated rat-derived osteoblasts (n = 3).

RESULTS

Significant increases in osteoblast senescence biomarkers were observed in both human and rat SCB with knee OA. These abnormalities, along with damaged cartilage integrity and SCB microarchitecture, were evident in rats with MIA-induced OA but were alleviated by rESWT, with the optimal dose being 0.096 mJ/mm. Significant mitigations in senescence and cell cycle disturbances were noted in rESWT-treated TNF-α-stimulated osteoblasts in vitro. No significant differences were found between rESWT and treadmill exercise, nor was there any further improvement after combining these 2 treatment methods.

CONCLUSION

In early-stage knee OA, rESWT alleviated SCB abnormalities, reducing osteoblast senescence and stabilizing the cell cycle. rESWT may serve as a supplementary or alternative treatment option, particularly when physical exercise is contraindicated.

CLINICAL RELEVANCE

rESWT alleviated SCB abnormalities and mitigated osteoblast senescence in early-stage OA, making it a potential supplementary treatment approach for some patients with OA.

摘要

背景

成骨细胞衰老导致的软骨下骨(SCB)过度周转已被确认为早期骨关节炎(OA)的组织学表现。桡侧体外冲击波疗法(rESWT)对早期OA中成骨细胞衰老的治疗效果尚未完全阐明。

目的

评估rESWT在增强膝骨关节炎大鼠模型中SCB成骨和减轻成骨细胞衰老方面的治疗潜力。

研究设计

对照实验室研究。

方法

通过免疫组织化学评估膝骨关节炎患者(n = 3)胫骨平台样本中衰老生物标志物的表达。在8周龄雄性Sprague-Dawley大鼠中建立碘乙酸钠(MIA)诱导的OA,用3种不同剂量的rESWT(0.096、0.128或0.16 mJ/mm;每组n = 6)治疗4周。收集关节软骨和SCB样本,使用组织学、放射学、免疫组织化学和免疫荧光技术进行分析,以评估rESWT的组织修复、成骨和抗衰老作用,并确定最佳治疗剂量。然后,使用一组新的MIA诱导的OA大鼠,分别接受rESWT、跑步机运动或联合治疗(每组n = 6),比较这3种方法对膝OA的治疗效果。对于体外分析,使用TNF-α刺激的大鼠成骨细胞(n = 3)进一步评估rESWT对衰老生物标志物的影响。

结果

在患有膝OA的人和大鼠SCB中均观察到成骨细胞衰老生物标志物显著增加。这些异常,连同受损的软骨完整性和SCB微结构,在MIA诱导的OA大鼠中很明显,但通过rESWT得到缓解,最佳剂量为0.096 mJ/mm。在体外rESWT处理的TNF-α刺激的成骨细胞中,衰老和细胞周期紊乱显著减轻。rESWT与跑步机运动之间未发现显著差异,将这两种治疗方法联合使用后也没有进一步改善。

结论

在早期膝OA中,rESWT减轻了SCB异常,减少了成骨细胞衰老并稳定了细胞周期。rESWT可作为一种补充或替代治疗选择,特别是在体育锻炼禁忌时。

临床相关性

rESWT减轻了早期OA中的SCB异常并减轻了成骨细胞衰老,使其成为一些OA患者的潜在补充治疗方法。

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