浏览全部资源
扫码关注微信
1, 25(OH)2D3通过调节Th17/Treg比值和RANKL/OPG轴缓解胶原诱导的关节炎
1, 25-dihydroxy vitamin D3 alleviates collagen-induced arthritis
via regulating Th17/Treg ratio and RANKL/OPG axis- 陆军军医大学学报 2023年45卷第15期 页码：1656-1665
- 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：
[唐雪梅，E-mail: tangxuemei2008@163.comTANG Xuemei, E-mail: tangxuemei2008@163.com
- 基金信息：基金项目］ 国家重点研发计划项目(2021YFC2702003)
DOI：10.16016/j.2097-0927.202302122
中图分类号： R684.3;R967;R977.2收稿：2023-02-22，
修回：2023-03-14，
纸质出版：2023-08-15
- 稿件说明：
移动端阅览
齐坤, 刘云, 唐滔, 等. 1, 25(OH)2D3通过调节Th17/Treg比值和RANKL/OPG轴缓解胶原诱导的关节炎[J]. 陆军军医大学学报, 2023,45(15):1656-1665.
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.齐坤, 刘云, 唐滔, 等. 1, 25(OH)2D3通过调节Th17/Treg比值和RANKL/OPG轴缓解胶原诱导的关节炎[J]. 陆军军医大学学报, 2023,45(15):1656-1665. DOI： 10.16016/j.2097-0927.202302122.
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
2
探讨1
25-二羟基维生素D
3
[1
25-dihydroxy vitamin D3，1
25(OH)
2
D
3
]
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
2
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)
2
D
3
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)
2
D
3
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
2
1
25(OH)
2
D
3
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(
P
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(
P
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(
P
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(
P
均
<
0.05)，NF-κB和RANKL蛋白水平明显低于CIA组(
P
均
<
0.05)，RANKL/OPG的比例也明显低于CIA组(
P
<
0.05)。
结论
2
1
25(OH)
2
D
3
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
2
To investigate the mechanisms of 1
25(OH)
2
D
3
on joint inflammation and bone destruction in a mouse model of collagen-induced arthritis (CIA).
Methods
2
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)
2
D
3
. 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)
2
D
3
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
2
1
25(OH)
2
D
3
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
P
<
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
P
<
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
P
<
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
P
<
0.05).
Conclusion
2
1
25(OH)
2
D
3
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
PRAKKEN B, ALBANI S, MARTINI A. Juvenile idiopathic arthritis[J]. Lancet, 2011, 377(9783): 2138-2149. DOI: 10.1016/S0140-6736(11)60244-4.
BARUT K, ADROVIC A, ŞAHIN S, et al . Juvenile idiopathic arthritis[J ] . Balkan Med J, 2017, 34(2): 90-101. DOI: 10.4274/balkanmedj.2017.0111.
HUANG F, WONG P, LI J L, et al . Osteoimmunology: The correlation between osteoclasts and the Th17/Treg balance in osteoporosis[J ] . J Cell Mol Med, 2022, 26(13): 3591-3597. DOI: 10.1111/jcmm.17399.
SATO K, SUEMATSU A, OKAMOTO K, et al . Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction[J ] . J Exp Med, 2006, 203(12): 2673-2682. DOI: 10.1084/jem.20061775.
FAN Z D, CAO Q, HUANG N, et al . MicroRNA-125b regulates Th17/Treg cell differentiation and is associated with juvenile idiopathic arthritis[J ] . World J Pediatr, 2020, 16(1): 99-110. DOI: 10.1007/s12519-019-00265-z.
ONO T, HAYASHI M, SASAKI F, et al . RANKL biology: bone metabolism, the immune system, and beyond[J ] . Inflamm Regen, 2020, 40: 2. DOI: 10.1186/s41232-019-0111-3.
UDAGAWA N, KOIDE M, NAKAMURA M, et al . Osteoclast differentiation by RANKL and OPG signaling pathways[J ] . J Bone Miner Metab, 2021, 39(1): 19-26. DOI: 10.1007/s00774-020-01162-6.
TAKAYANAGI H. Osteoimmunology and the effects of the immune system on bone[J]. Nat Rev Rheumatol, 2009, 5(12): 667-676. DOI: 10.1038/nrrheum.2009.217.
BOYCE B F, XING L P. Functions of RANKL/RANK/OPG in bone modeling and remodeling[J]. Arch Biochem Biophys, 2008, 473(2): 139-146. DOI: 10.1016/j.abb.2008.03.018.
SARMA P K, MISRA R, AGGARWAL A. Elevated serum receptor activator of NFκB ligand (RANKL), osteoprotegerin (OPG), matrix metalloproteinase (MMP) 3 , and ProMMP1 in patients with juvenile idiopathic arthritis[J ] . Clin Rheumatol, 2008, 27(3): 289-294. DOI: 10.1007/s10067-007-0701-3.
CHAROENNGAM N. Vitamin D and rheumatic diseases: a review of clinical evidence[J]. Int J Mol Sci, 2021, 22(19): 10659. DOI: 10.3390/ijms221910659.
CHRISTAKOS S, DHAWAN P, VERSTUYF A, et al . Vitamin D: metabolism, molecular mechanism of action, and pleiotropic effects[J ] . Physiol Rev, 2016, 96(1): 365-408. DOI: 10.1152/physrev.00014.2015.
MARTENS P, GYSEMANS C, VERSTUYF A, et al . Vitamin D's effect on immune function[J ] . Nutrients, 2020, 12(5): 1248. DOI: 10.3390/nu12051248.
FENG X K, LV C Y, WANG F, et al . Modulatory effect of 1, 25-dihydroxyvitamin D 3 on IL1β-induced RANKL, OPG, TNFα, and IL-6 expression in human rheumatoid synoviocyte MH7A[J ] . Clin Dev Immunol, 2013, 2013: 1-8. DOI: 10.1155/2013/160123..
KONDRATYEVA E I, ODINAEVA N D, KLIMOV L Y, et al . Vitamin D status among children with juvenile idiopathic arthritis: amulticenter prospective, non-randomized, comparative study[J ] . Front Pediatr, 2022, 10: 915943. DOI: 10.3389/fped.2022.915943.
TANG T, ZHANG Y, LUO C, et al . Adjunctive vitamin D for the tr eatment of active juvenile idiopathic arthritis: an open-label, prospective, randomized controlled trial[J ] . Exp Ther Med, 2019, 18(6): 4921-4926. DOI: 10.3892/etm.2019.8133.
NANDI M, MULLICK M A S, NANDY A, et al . Evaluation of vitamin D profile in juvenile idiopathic arthritis[J ] . Mod Rheumatol, 2022, 32(4): 792-796. DOI: 10.1093/mr/roab053.
SENGLER C, ZINK J, KLOTSCHE J, et al . Vitamin D deficiency is associated with higher disease activity and the risk for uveitis in juvenile idiopathic arthritis—data from a German inception cohort[J ] . Arthritis Res Ther, 2018, 20(1): 276. DOI: 10.1186/s13075-018-1765-y.
ZHOU L, WANG J L, LI J R, et al . 1, 25-dihydroxyvitamin D3 ameliorates collagen-induced arthritis via suppression of Th17 cells through miR-124 mediated inhibition of IL-6 signaling[J ] . Front Immunol, 2019, 10: 178. DOI: 10.3389/fimmu.2019.00178..
WANG Z J, HUANG W H, REN F F, et al . Characteristics of ang-(1-7)/mas-mediated amelioration of joint inflammation and cardiac complications in mice with collagen-induced arthritis[J ] . Front Immunol, 2021, 12: 655614. DOI: 10.3389/fimmu.2021.655614.
FENG N B, LIANG L, FAN M T, et al . Treating autoimmune inflammatory diseases with an siERN1-nanoprodrug that mediates macrophage polarization and blocks toll-like receptor signaling[J ] . ACS Nano, 2021, 15(10): 15874-15891. DOI: 10.1021/acsnano.1c03726.
VAN NIEUWENHOVE E, LAGOU V, VAN EYCK L, et al . Machine learning identifies an immunological pattern associated with multiple juvenile idiopathic arthritis subtypes[J ] . Ann Rheum Dis, 2019, 78(5): 617-628. DOI: 10.1136/annrheumdis-2018-214354.
POUTOGLIDOU F, POURZITAKI C, MANTHOU M E, et al . Infliximab and tocilizumab reduce anxiety-like behaviour and improve cognitive performance in a juvenile collagen-induced arthritis rat model[J ] . Inflammation, 2022, 45(1): 445-459. DOI: 10.1007/s10753-021-01560-6.
POUTOGLIDOU F, POURZITAKI C, MANTHOU M E, et al . The inhibitory effect of tocilizumab on systemic bone loss and tendon inflammation in a juvenile collagen-induced arthritis rat model[J ] . Connect Tissue Res, 2022, 63(6): 577-589. DOI: 10.1080/03008207.2022.2042275.
LORENZO N, CANTERA D, BARBERÁ A, et al . APL-2, an altered peptide ligand derived from heat-shock protein 60, induces interleukin -10 in peripheral blood mononuclear cell derived from juvenile idiopathic arthritis patients and downregulates the inflammatory response in collagen-induced arthritis model[J ] . Clin Exp Med, 2015, 15(1): 31-39. DOI: 10.1007/s10238-014-0273-x.
MARTINI A, LOVELL D J, ALBANI S, et al . Juvenile idiopathic arthritis[J ] . Nat Rev Dis Primers, 2022, 8: 5. DOI: 10.1038/s41572-021-00332-8.
AESCHLIMANN F A, CHONG S L, LYONS T W, et al . Risk of serious infections associated with biologic agents in juvenile idiopathic arthritis: a systematic review and meta-analyses[J ] . J Pediatr, 2019, 204: 162-171. e3. DOI: 10.1016/j.jpeds.2018.08.065.
STEEVE K T, MARC P, SANDRINE T, et al . IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology[J ] . Cytokine Growth Factor Rev, 2004, 15(1): 49-60. DOI: 10.1016/j.cytogfr.2003.10.005.
WADA T, NAKASHIMA T, HIROSHI N, et al . RANKL-RANK signaling in osteoclastogenesis and bone disease[J ] . Trends Mol Med, 2006, 12(1): 17-25. DOI: 10.1016/j.molmed.2005.11.007.
HONG G J, ZHOU L, SHI X G, et al . B ajijiasu abrogates osteoclast differentiation via the suppression of RANKL signaling pathways through NF-κB and NFAT[J ] . Int J Mol Sci, 2017, 18(1): 203. DOI: 10.3390/ijms18010203..
FERNANDEZ LAHORE G, RAPOSO B, LAGERQUIST M, et al . Vitamin D3 receptor polymorphisms regulate T cells and T cell-dependent inflammatory diseases[J ] . Proc Natl Acad Sci USA, 2020, 117(40): 24986-24997. DOI: 10.1073/pnas.2001966117.
0
浏览量
0
下载量
0
CSCD
- 网络PDF下载
- Meta-XML下载
- BibTeX下载
- Endnote下载
- RefMan 下载
- NoteExpress下载
- NoteFirst下载
关联资源
相关文章
相关作者
相关机构
- 技术支持由北京北大方正电子有限公司提供 京ICP备09064830号-19
京公网安备11010802024621 - 本系统建议在Chrome、 IE9+ 以上版本浏览器阅读本站内容，360浏览器请切换至极速模式
- Cookies帮助我们提供服务并提供个性化体验。使用本网站，即表示您同意我们使用Cookies
