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成骨前体细胞中孕激素受体选择性抑制的小鼠对胶原诱导性关节炎高度敏感。

High susceptibility to collagen-induced arthritis in mice with progesterone receptors selectively inhibited in osteoprogenitor cells.

机构信息

Department of Internal Medicine, University of California, Davis Medical Center, 4625 2nd Avenue, Sacramento, CA, 95817, USA.

Faculty of Animal Science and Technology, Yunnan Agricultural University, Kunming, Yunnan, People's Republic of China.

出版信息

Arthritis Res Ther. 2020 Jul 2;22(1):165. doi: 10.1186/s13075-020-02242-8.

DOI:10.1186/s13075-020-02242-8
PMID:32616012
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7331177/
Abstract

BACKGROUND

Progesterone receptor (PR) affects immunomodulation, and lack of PR in osteoprogenitor cells primarily affects pathways associated with immunomodulation, especially in males. In this study, we selectively deleted PR from osteoprogenitor cells using Prx1-Cre to evaluate the tissue-specific effects of PR on the pathegenesis of inflammatary arthritis (IA).

METHODS

Collagen-induced arthritis (CIA) was used as an IA animal model. Both male and female PR mice and their wild-type (WT) littermates were immunized with collagen II (CII) emulsified complete Freund's adjuvant (CFA). Joint erosion, inflammation, and cartilage damage were assessed using a semiquantitative histologic scoring system. Bone volume and erosions in knee and ankle joints were quantitated using microCT and histology.

RESULTS

Bone erosions developed in both paw joints in 37.5% and 41.7% of the WT and PR female mice and in 45.4 and 83.3% of the WT and PR male mice, respectively. Also, both joint damage and subchondral bone erosions were significantly more severe in male PRcKO-CIA mice than in male WT-CIA mice. Female PR mice also developed higher bone loss in the knee joints than the KO-normal or WT-CIA females although with less severity compared to the male mice.

CONCLUSIONS

The presence of PR in osteoprogenitor cells decreased the development of collagen-induced arthritis and might help to explain the sex differences observed in human inflammatory arthritis.

摘要

背景

孕激素受体（PR）影响免疫调节，成骨前体细胞中缺乏 PR 主要影响与免疫调节相关的途径，尤其是在男性中。在这项研究中，我们使用 Prx1-Cre 选择性地从成骨前体细胞中删除 PR，以评估 PR 对炎性关节炎（IA）发病机制的组织特异性影响。

方法

胶原诱导性关节炎（CIA）被用作 IA 动物模型。PR 基因敲除（PRcKO）和野生型（WT）同窝仔鼠分别用 II 型胶原（CII）乳化完全弗氏佐剂（CFA）免疫。采用半定量组织学评分系统评估关节侵蚀、炎症和软骨损伤。使用 microCT 和组织学定量评估膝关节和踝关节的骨体积和侵蚀。

结果

WT 和 PR 雌性小鼠的爪子关节中分别有 37.5%和 41.7%出现骨侵蚀，WT 和 PR 雄性小鼠的爪子关节中分别有 45.4%和 83.3%出现骨侵蚀。此外，雄性 PRcKO-CIA 小鼠的关节损伤和软骨下骨侵蚀均明显比雄性 WT-CIA 小鼠严重。尽管与雄性小鼠相比，雌性 PR 小鼠的膝关节骨丢失更为严重，但也比 KO 正常或 WT-CIA 雌性小鼠更为严重。

结论

成骨前体细胞中 PR 的存在可降低胶原诱导性关节炎的发生，这可能有助于解释人类炎性关节炎中观察到的性别差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757d/7331177/8c0e5dde3ffd/13075_2020_2242_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757d/7331177/f1c187590d68/13075_2020_2242_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757d/7331177/2764d582891a/13075_2020_2242_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757d/7331177/f2c5f2c95437/13075_2020_2242_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757d/7331177/0f8694ae40e3/13075_2020_2242_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757d/7331177/8e08f9a82e9d/13075_2020_2242_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757d/7331177/8c0e5dde3ffd/13075_2020_2242_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757d/7331177/f1c187590d68/13075_2020_2242_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757d/7331177/2764d582891a/13075_2020_2242_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757d/7331177/f2c5f2c95437/13075_2020_2242_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757d/7331177/0f8694ae40e3/13075_2020_2242_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757d/7331177/8e08f9a82e9d/13075_2020_2242_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/757d/7331177/8c0e5dde3ffd/13075_2020_2242_Fig6_HTML.jpg

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