1, 25-dihydroxy vitamin D<sub>3</sub> alleviates collagen-induced arthritis <italic style="font-style: italic">via</italic> regulating Th17/Treg ratio and RANKL/OPG axis

Kun QI; Yun LIU; Tao TANG; Xiwen LUO; Yu ZHANG; Zhiyong ZHANG; Yunfei AN; Xuemei TANG

doi:10.16016/j.2097-0927.202302122

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1, 25-dihydroxy vitamin D₃ alleviates collagen-induced arthritis via regulating Th17/Treg ratio and RANKL/OPG axis

Basic Medicine | 更新时间：2026-01-09

- 1, 25-dihydroxy vitamin D₃ alleviates collagen-induced arthritis via regulating Th17/Treg ratio and RANKL/OPG axis
- Journal of Army Medical University Vol. 45, Issue 15, Pages: 1656-1665(2023)
- 作者机构：
  
  400014 重庆，重庆医科大学附属儿童医院风湿免疫科，国家儿童健康与疾病临床医学研究中心，儿童发育疾病研究教育部重点实验室，重庆市儿童感染与免疫重点实验室
- 作者简介：
- 基金信息：
  
  the National Key R&D Program of China(2021YFC2702003)
- DOI：10.16016/j.2097-0927.202302122
  CLC： R684.3;R967;R977.2
- Received：22 February 2023，
  
  Revised：2023-03-14，
  
  Published：15 August 2023
- 稿件说明：
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Kun QI, Yun LIU, Tao TANG, et al. 1, 25-dihydroxy vitamin D₃ alleviates collagen-induced arthritis via regulating Th17/Treg ratio and RANKL/OPG axis[J]. Journal of Army Medical University, 2023, 45(15): 1656-1665.
DOI：

Kun QI, Yun LIU, Tao TANG, et al. 1, 25-dihydroxy vitamin D₃ alleviates collagen-induced arthritis via regulating Th17/Treg ratio and RANKL/OPG axis[J]. Journal of Army Medical University, 2023, 45(15): 1656-1665. DOI： 10.16016/j.2097-0927.202302122.

摘要

目的

探讨1

25-二羟基维生素D

25-dihydroxy vitamin D3，1

25(OH)

]

对胶原诱导的关节炎(collagen-induced arthritis，CIA)模型小鼠关节滑膜炎症和骨破坏的抑制作用及机制。

方法

30只DBA/1J小鼠被均分为3组: 对照组(CON)、模型组(CIA)和模型干预组(VD)。CIA组和VD组小鼠建立CIA模型，用1

25(OH)

对VD组CIA模型进行治疗。用游标卡尺测量小鼠后足爪的肿胀程度。用Micro-CT测量小鼠后足爪的骨密度。酶联免疫吸附剂测定法检测小鼠血清1

25(OH)

和炎症细胞因子(IL-1β、IL-6、TNF-α)的水平。流式细胞术检测小鼠脾脏Th17细胞和Treg细胞的比例。采用苏木精-伊红染色观察膝关节的病理特征。Western blot检测小鼠踝关节的蛋白OPG、RANKL、NF-κB和VDR的表达水平。

结果

25(OH)

并没有降低CIA模型的发病率，但却明显缓解了关节炎症。VD组的脚掌厚度、关节炎评分以及膝关节HSS评分均较CIA组明显降低(

均

0.05)。CIA组的骨破坏程度更加明显，BMD及BV/TV明显低于VD组(

均

0.05)。VD组的IL-1β、IL-6、TNF-α水平和Th17/Treg细胞比例明显低于CIA组(

均

0.05)。与CIA组相比，VD组踝关节的VDR和OPG蛋白水平明显增加(

均

0.05)，NF-κB和RANKL蛋白水平明显低于CIA组(

均

0.05)，RANKL/OPG的比例也明显低于CIA组(

0.05)。

结论

25(OH)

可能通过调节Th17/Treg比值和RANKL/OPG轴缓解CIA模型小鼠的关节滑膜炎症并抑制骨破坏。

Abstract

Objective

To investigate the mechanisms of 1

25(OH)

on joint inflammation and bone destruction in a mouse model of collagen-induced arthritis (CIA).

Methods

Thirty DBA/1J mice were equally allocated into control

CIA and intervention (VD) groups. The CIA model was established in the mice in the CIA group and VD group

meanwhile the VD group was treated with 1

25(OH)

. The thickness of the hind

foot paws was measured with vernier caliper. Micro-CT scanning was used to measure bone mineral density (BMD) of the hindfoot paw

ELISA was employed to detect the serum levels of 1

25(OH)

and proinflammatory cytokines (IL-1β

IL-6

TNF-α)

and flow cytometry was performed to calculate the ratio of Th17 to Treg cells in the spleen. The pathological changes of the knee joint were observed with HE staining. Western blotting was applied to detect the expression levels of osteoprotegerin (OPG)

receptor activator of nuclear factor-κB ligand (RANKL)

NF-κB

and vitamin D receptor (VDR) in mouse ankle joints.

Results

25(OH)

did not reduce the incidence of CIA in the of mice in the VD group

but significantly reduced joint inflammation. Obviously decreased thickness of the hindfoot paw

arthritis score

and knee histological synovitis score (HSS) were observed in the VD group than the CIA group (all

0.05). The CIA group presented more serious bone destruction and lower BMD and bone volume fraction (BV/TV) when compared with the VD group (both

0.05). The serum levels of IL-1β

IL-6 and TNF-α and ratio of Th17/Treg cells in the VD group were statistically lower than those in the CIA group (all

0.05). Compared with the CIA group

the VD group had notably higher protein levels of VDR and OPG

lower levels of NF-κB and RANKL

and reduced RANKL/OPG ratio in the ankle joint (all

0.05).

Conclusion

25(OH)

may alleviate arthritic inflammation and suppress bone destruction in the mouse CIA model

via

regulating the Th17/Treg ratio and the RANKL/OPG axis.

关键词

Keywords

references

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⁰

1, 25-dihydroxy vitamin D3 alleviates collagen-induced arthritis via regulating Th17/Treg ratio and RANKL/OPG axis

DOI：10.16016/j.2097-0927.202302122

摘要

Abstract

关键词

Keywords

references

1, 25-dihydroxy vitamin D₃ alleviates collagen-induced arthritis via regulating Th17/Treg ratio and RANKL/OPG axis