The role of total and cartilage-specific estrogen receptor alpha expression for the ameliorating effect of estrogen treatment on arthritis.
The role of total and cartilage-specific estrogen receptor alpha expression for the ameliorating effect of estrogen treatment on arthritis.
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DOI：
10.1186/ar4612
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发表时间：
2014-07-15
影响因子：
4.9
通讯作者：
Lagerquist MK
中科院分区：
文献类型：
--
作者：
Engdahl C;Börjesson AE;Forsman HF;Andersson A;Stubelius A;Krust A;Chambon P;Islander U;Ohlsson C;Carlsten H;Lagerquist MK
雌激素(E_2)可延缓实验性关节炎的发病并降低其严重程度。本研究的目的是探讨转基因小鼠总雌激素受体α(ERα)表达和软骨特异性ERα表达对雌激素改善实验性关节炎疗效的重要性。全部(总ERα-/-)或软骨特异性(Col2α1-ERα-/-)ERα和野生型(WT)产仔失活的小鼠被摘除卵巢，用E2或安慰剂治疗，并诱导抗原诱导的关节炎。治疗结束后，取膝关节作组织学检查，用流式细胞仪检测滑膜细胞和脾细胞，用T细胞增殖试验检测脾细胞。E_2可减少WT小鼠滑膜炎和关节破坏。关节炎的改善与滑膜组织中炎症细胞的减少和脾T细胞的增殖减少有关。雌二醇对ERα-/-小鼠的滑膜炎或关节破坏无影响。在COL2α1-ERα-/-小鼠中，E2保护关节免受破坏的程度与WT小鼠相似。相反，E2并没有显著改善COL2α1-ERα-/-小鼠的滑膜炎。雌激素通过ERα改善去卵巢小鼠的滑膜炎和关节破坏。关节炎严重程度的降低与滑膜炎症细胞频率降低和脾T细胞增殖减少有关。ERα在软骨中的表达不是雌激素改善关节破坏所必需的。然而，我们的数据表明，ERα在软骨中的表达参与了雌激素对滑膜炎的影响，提示E2改善关节破坏和滑膜炎症的机制不同。
Estrogen (E2) delays onset and decreases severity of experimental arthritis. The aim of this study was to investigate the importance of total estrogen receptor alpha (ERα) expression and cartilage-specific ERα expression in genetically modified mice for the ameliorating effect of estrogen treatment in experimental arthritis. Mice with total (total ERα-/-) or cartilage-specific (Col2α1-ERα-/-) inactivation of ERα and wild-type (WT) littermates were ovariectomized, treated with E2 or placebo, and induced with antigen-induced arthritis (AIA). At termination, knees were collected for histology, synovial and splenic cells were investigated by using flow cytometry, and splenic cells were subjected to a T-cell proliferation assay. E2 decreased synovitis and joint destruction in WT mice. Amelioration of arthritis was associated with decreased frequencies of inflammatory cells in synovial tissue and decreased splenic T-cell proliferation. E2 did not affect synovitis or joint destruction in total ERα-/- mice. In Col2α1-ERα-/- mice, E2 protected against joint destruction to a similar extent as in WT mice. In contrast, E2 did not significantly ameliorate synovitis in Col2α1-ERα-/- mice. Treatment with E2 ameliorates both synovitis and joint destruction in ovariectomized mice with AIA via ERα. This decreased severity in arthritis is associated with decreased synovial inflammatory cell frequencies and reduced splenic T-cell proliferation. ERα expression in cartilage is not required for estrogenic amelioration of joint destruction. However, our data indicate that ERα expression in cartilage is involved in estrogenic effects on synovitis, suggesting different mechanisms for the amelioration of joint destruction and synovitis by E2.
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影响因子：
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作者：
Itou, Takuya;Collins, L. Vincent;Karlsson, Anna
通讯作者：
Karlsson, Anna
影响因子：
6.1
作者：
ITO, I;HAYASHI, T;IGUCHI, A
通讯作者：
IGUCHI, A
影响因子：
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作者：
Jochems, Caroline;Islander, Ulrika;Carlsten, Hans
通讯作者：
Carlsten, Hans
影响因子：
--
作者：
Grespan, Renata;Fukada, Sandra Y.;Cunha, Fernando Q.
通讯作者：
Cunha, Fernando Q.
影响因子：
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作者：
Doran, MF;Pond, GR;Gabriel, SE
通讯作者：
Gabriel, SE