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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

31卷

期数:

2025年05期

页码:

396-403

栏目:

骨病专题

出版日期:

2025-09-20

文章信息/Info

Title:

Static magnetic field inhibits TRPV4-mediated osteoclast biological behavior to alleviate osteoarthritis

文章编号:

1006-8147(2025)05-0396-08

作者:

康冉¹; 李心乐¹; 方彦雯²; 卫敏²; 廖钟财²; 杨磊³; 张平¹; 3

1.天津医科大学基础医学院人体解剖学系，天津 300070；2.和也健康科技有限公司，安吉313399；3.河北工业大学生命科学与健康工程学院，健康科学与工程研究中心，河北省生物医学材料与智能诊疗重点实验室，天津 300401

Author(s):

KANG Ran¹;  LI Xinle¹;  FANG Yanwen²;  WEI Min²;  LIAO Zhongcai²;  YANG Lei³;  ZHANG Ping¹; 3

1.Department of Anatomy， School of Basic Medical Sciences， Tianjin Medical University， Tianjin 300070， China； 2.Heye Health Technology Co.， Ltd.， Anji 313399， China； 3.Center for Health Science and Engineering， Hebei Key Laboratory of Biomaterials and Smart Theranostics， School of Health Sciences and Biomedical Engineering， Hebei University of Technology， Tianjin 300401， China

关键词:

静磁场; 骨关节炎; 瞬时受体电位香草蛋白4; 破骨细胞

Keywords:

static magnetic field;  osteoarthritis;  TRPV4;  osteoclasts

分类号:

R684.3

DOI:

10.20135/j.issn.1006-8147.2025.05.0396

文献标志码:

A

摘要:

目的：探讨瞬时受体电位香草蛋白4（TRPV4）在骨关节炎小鼠中的表达变化以及静磁场影响破骨细胞行为和修复软骨下骨吸收驱动的软骨退变的机制。方法：本研究采用SPF级雌性C57BL/6小鼠70只。在实验的第一部分将其按随机字数表法分为对照组（Control组， n=10）和骨关节炎组（n=30），后者根据造模时间分为OA7d组（n=10）、OA14d组（n=10）、OA28d组（n=10）。免疫组化检测TRPV4在不同造模时间软骨下骨中的表达。在实验的第二部分将C57BL/6小鼠按随机字数表法分为假手术组（Sham组，n=10）、骨关节炎组（OA组， n=10）、骨关节炎联合静磁场治疗组（OAS组，n=10）。采用横断内侧副韧带，切除内侧半月板的方法建立骨关节炎小鼠模型，并使用本实验室特制的200 mT的静磁场干预2周。通过组织学染色评估静磁场对软骨退变及软骨下骨病理的影响。免疫组化染色评估体内静磁场对TRPV4表达的影响。体外分离骨髓源性破骨细胞，采用TRPV4拮抗剂GSK219验证静磁场对破骨细胞形成、迁移、黏附的作用。ELISA法检测血清和破骨细胞条件培养基中肿瘤坏死因子α（TNF-α）水平。破骨细胞条件培养基培养ATDC5细胞，观察破骨细胞对软骨细胞退变的影响。结果：实验第一部分免疫组化结果显示骨关节炎小鼠软骨下骨中TRPV4阳性表面呈时间依赖性上调。实验第二部分组织学染色显示静磁场改善软骨下骨微结构，提高骨小梁面积比（t=4.318， P<0.01）及软骨下骨板厚度（t=10.42， P<0.001），并且降低骨关节炎小鼠国际骨关节炎研究协会评分（t=3.614，P<0.05），改善软骨损伤；静磁场通过抑制TRPV4降低破骨细胞形成、迁移和黏附能力（t=26.35、36.56、35.76， 均P<0.001）；且TRPV4拮抗剂GSK219可模拟静磁场效应。静磁场降低破骨细胞分泌的TNF-α水平（t=3.935， P<0.01），减少其对软骨细胞退变的作用（t=28.52， P<0.001）。结论：骨关节炎早期软骨下骨中TRPV4表达呈时间依赖性增加。静磁场通过抑制TRPV4介导的破骨细胞生物学行为，改善软骨下骨吸收及继发软骨退变。

Abstract:

Objective： To investigate the expression changes of transient receptor potential vanilloid 4（TRPV4） in osteoarthritis（OA） and the mechanism by which static magnetic fields（SMF） influence the biological behavior of osteoclasts and repair subchondral bone resorption-driven cartilage degeneration. Methods： Seventy SPF grade female C57BL/6 mice were used in this study. In the first part of the experiment， C57BL/6 mice were divided into control group（Control， n=10） and osteoarthritis group（OA， n=30） according to the random number table method. The OA group was further divided into OA7d group（n=10）， OA14d group（n=10） and OA28d group（n=10） according to the time of 7， 14 and 28 days of modeling. The expression of TRPV4 in subchondral bone at different time points was detected by immunohistochemistry. In the second part of the experiment， C57BL/6 mice were randomly divided into sham operation group（Sham group， n=10）， osteoarthritis group（OA group， n=10）， osteoarthritis combined with static magnetic field trea-tment group（OAS group， n=10） according to the random number table method. A mouse model of OA was established by transection of the medial collateral ligament and resection of the medial meniscus. The mice were treated with a 200 mT static magnetic field specially designed in our laboratory for 2 weeks. Histological staining was used to evaluate the effect of static magnetic field on cartilage degeneration and subchondral bone pathology. Immunohistochemical staining was used to evaluate the effect of static magnetic field on TRPV4 expression in vivo. Bone marrow derived osteoclasts were isolated in vitro， and the effects of static magnetic field on osteoclast formation， migration and adhesion were verified using TRPV4 antagonist GSK219. The levels of tumor necrosis factor-α （TNF-α） in serum and osteoclast conditioned medium were detected by ELISA. ATDC5 cells were cultured in osteoclast conditioned medium to observe the effect of osteoclasts on the degeneration of chondrocytes. Results： In the first part of the experiment， immunohistochemistry results showed a time-dependent upregulation of TRPV4 positive surface in subchondral bone of OA mice. In the second part of the experiment， histological staining showed that static magnetic field improved the microstructure of subchondral bone， increased the area ratio of trabecular bone （t=4.318， P<0.01） and subchondral bone plate thickness （t=10.42， P<0.001）， reduced Osteoarthritis Research Society International（OARSI） score （t=3.614， P<0.05）， and improved cartilage damage in OA mice. Static magnetic field inhibited the formation， migration and adhesion of osteoclasts by inhibiting TRPV4 （t=26.35， 36.56， 35.76， all P<0.001）. GSK219， a TRPV4 antagonist， could mimic the static magnetic field effect. Static magnetic field decreased the level of TNF-α secreted by osteoclasts（t=3.935， P<0.01） and reduced its effect on the degeneration of chondrocytes（t=28.52， P<0.001）. Conclusion： TRPV4 expression in subchondral bone increases in a time-dependent manner in the early stage of OA. Static magnetic field can improve subchondral bone resorption and secondary cartilage degeneration by inhibiting the biological behavior of TRPV4-mediated osteoclasts.

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备注/Memo

备注/Memo:

基金项目:国家自然科学基金（81772405，81572100）；和也健康科技重明鸟计划（2021006，2022016）
作者简介:康冉(1998-)，女，硕士在读，研究方向：静磁场治疗骨关节炎的机制研究；通信作者:张平，E-mail:pizhang2008@163.com。

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更新日期/Last Update: 2025-10-01