S100A8/A9 is not essential for the development of inflammation and joint pathology in interleukin-1 receptor antagonist knockout mice.
S100A8/A9 is not essential for the development of inflammation and joint pathology in interleukin-1 receptor antagonist knockout mice.
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DOI：
10.1186/s13075-021-02602-y
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发表时间：
2021-08-19
影响因子：
4.9
通讯作者：
van den Bosch MHJ
中科院分区：
文献类型：
--
作者：
Di Ceglie I;van Lent PLEM;Geven EJW;Koenders MI;Blom AB;Vogl T;Roth J;van den Bosch MHJ
过度的破骨细胞活性，这是强烈刺激的促炎介质，导致骨和软骨退化的许多关节炎的中心特征。Alarmin S100 A8/A9和白细胞介素（IL）-1β的水平在关节炎患者中均升高，并与疾病活动和组织侵蚀的进展相关。我们之前提出S100 A8/A9是在缺乏编码IL-1受体拮抗剂基因的小鼠（Il 1 rn −/−小鼠）中高IL-1信号传导的情况下关节炎症和关节炎病理学的良好生物标志物。在这里，我们研究了S100 A8/A9是否也积极参与关节炎症的发展，并通过比较Il 1 rn −/−小鼠与S100 a9（Il 1 rn −/− XS 100 a9 −/−）的额外缺陷小鼠来研究这些条件下的软骨和骨病理学。通过将S100 a9 −/−小鼠和Il 1 rn −/−小鼠杂交获得BALB/c背景下的Il 1 rn −/− XS 100 a9 −/−。对关节炎发生率和严重程度进行肉眼评分。使用流式细胞术测定骨髓和脾脏中的髓样细胞群。TRAP染色观察骨髓细胞体外破骨细胞生成情况。使用12周龄和20周龄小鼠踝关节的组织学评价显微镜下关节炎症、软骨退化和骨破坏。在Il 1 rn −/−和Il 1 rn −/− XS 100 a9 −/−小鼠之间，关节炎严重程度的宏观评分相当。炎症、软骨侵蚀和骨质侵蚀明显存在于缺乏Il 1 rn −/−的两种品系的12周龄小鼠中，但在Il 1 rn −/− XS 100 a9 −/−和Il 1 rn −/−之间没有显著差异。此外，我们观察到，中性粒细胞和单核细胞的数量增加的IL 1 rn的情况下，这是受S100 a9的情况下，只有在脾脏，但不是在骨髓中。与我们的其他研究结果一致，S100 a9的缺失并不影响IL 1 rn缺失时破骨细胞前体的破骨细胞生成潜能。最后，与12周龄小鼠早期关节炎发展的发现一致，20周龄小鼠的软骨和骨质侵蚀在两种Il 1 rn −/−品系中均显著较高，但S100 a9的额外缺失并未进一步影响组织病理学。S100 A8/A9缺乏不会显著影响具有高IL 1 β信号传导的小鼠的炎症和关节破坏，表明S100 A8/A9对于在这些条件下关节炎的发展不是必需的。在线版本包含补充材料，可通过10.1186/s13075-021-02602-y获得。
Excessive osteoclast activity, which is strongly stimulated by pro-inflammatory mediators, results in bone and cartilage degeneration as central features of many arthritides. Levels of the alarmin S100A8/A9 and interleukin (IL)-1β are both increased in arthritis patients and correlate with disease activity and progression of tissue erosion. We previously presented S100A8/A9 as a good biomarker for joint inflammation and arthritis pathology under circumstances of high IL-1 signaling in mice that lack the gene encoding IL-1 receptor antagonist (Il1rn−/− mice). Here, we investigated whether S100A8/A9 is also actively involved in the development of joint inflammation and both cartilage and bone pathology under these conditions by comparing Il1rn−/− mice with mice that have an additional deficiency for S100a9 (Il1rn−/−XS100a9−/−). Il1rn−/−XS100a9−/− on a BALB/c background were obtained by crossing S100a9−/− mice and Il1rn−/− mice. Arthritis incidence and severity were macroscopically scored. Myeloid cell populations in the bone marrow and spleen were determined using flow cytometry. In vitro osteoclastogenesis of bone marrow cells was evaluated with TRAP staining. Microscopic joint inflammation, cartilage degeneration, and bone destruction were evaluated using histology of ankle joints of 12- and 20-week-old mice. Macroscopically scored arthritis severity was comparable between Il1rn−/− and Il1rn−/−XS100a9−/− mice. Inflammation, cartilage erosion, and bone erosion were clearly present in 12-week-old mice of both strains lacking Il1rn−/−, but not significantly different between Il1rn−/−XS100a9−/− and Il1rn−/−. Moreover, we observed that the numbers of neutrophils and monocytes were increased by the absence of Il1rn, which was affected by the absence of S100a9 only in the spleen but not in the bone marrow. In line with our other findings, the absence of S100a9 did not affect the osteoclastogenic potential of osteoclast precursors in the absence of Il1rn. Finally, in agreement with the findings in early arthritis development in 12-week-old mice, cartilage and bone erosion in 20-week-old mice was significantly higher in both Il1rn−/− strains, but the additional absence of S100a9 did not further affect tissue pathology. S100A8/A9 deficiency does not significantly affect inflammation and joint destruction in mice with high IL1β signaling suggesting that S100A8/A9 is not essential for the development of arthritis under these conditions. The online version contains supplementary material available at 10.1186/s13075-021-02602-y.
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DOI：
10.1084/jem.191.2.313
发表时间：
2000-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Horai R;Saijo S;Tanioka H;Nakae S;Sudo K;Okahara A;Ikuse T;Asano M;Iwakura Y
通讯作者：
Iwakura Y
影响因子：
27.4
作者：
Hammer, H. Berner;Odegard, S.;Kvien, T. K.
通讯作者：
Kvien, T. K.
影响因子：
4.9
作者：
Hammer HB;Fagerhol MK;Wien TN;Kvien TK
通讯作者：
Kvien TK
DOI：
10.1038/nrrheum.2012.153
发表时间：
2012-11
期刊：
Nature reviews. Rheumatology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1084/jem.191.2.303
发表时间：
2000-01-17
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Nicklin MJ;Hughes DE;Barton JL;Ure JM;Duff GW
通讯作者：
Duff GW