S100A8/A9 increases the mobilization of pro-inflammatory Ly6C(high) monocytes to the synovium during experimental osteoarthritis.
S100A8/A9 increases the mobilization of pro-inflammatory Ly6C(high) monocytes to the synovium during experimental osteoarthritis.
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DOI：
10.1186/s13075-017-1426-6
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发表时间：
2017-09-29
影响因子：
4.9
通讯作者：
van Lent PLEM
中科院分区：
文献类型：
--
作者：
Cremers NAJ;van den Bosch MHJ;van Dalen S;Di Ceglie I;Ascone G;van de Loo F;Koenders M;van der Kraan P;Sloetjes A;Vogl T;Roth J;Geven EJW;Blom AB;van Lent PLEM
在骨关节炎(OA)中，单核细胞是炎症滑膜中的优势细胞。在小鼠中，描述了两个功能不同的单核细胞亚群：促炎症的Ly6Chigh和巡逻的Ly6Clow单核细胞。炎症性骨关节炎时滑膜长期局部释放的S100A8/A9可能是刺激Ly6 Chigh单核细胞从循环向关节募集的主要蛋白。我们的目的是探讨S100A8/A9在胶原酶诱导的骨性关节炎(CiOA)中动员Ly6Chigh和Ly6Clow单核细胞到炎症关节的作用。关节腔内注射S100A8观察单核细胞内流情况。C57BL/6(WT)野生型和S100A9-/-小鼠膝关节内注射胶原酶诱导CIOA。与年龄匹配的生理盐水对照组(n = 6/组)一起处死小鼠，用ELISA法和RT-qPCR法检测滑膜中单核细胞标志物、促炎细胞因子和趋化因子的表达。从骨髓、脾、血和滑膜中分离细胞，用流式细胞仪鉴定单核细胞。S100A8/A9在CIOA中高表达。关节腔内注射S100A8可导致滑膜中单核细胞标志物和单核细胞趋化因子CCL2和CX3CL1表达增加。在WT小鼠诱导CiOA后的第7天(D7)，滑膜中Ly6Chigh的数量显著增加(7.6倍)，而Ly6Clow的单核细胞数量没有明显增加。这与CCL2的强烈上调相吻合，CCL2优先吸引Ly6Chigh单核细胞。相比之下，S100A9-/-小鼠滑膜中Ly6Clow单核细胞显著增加(两倍)，而Ly6Chigh单核细胞数量保持不变。与这一发现一致的是，Ly6Clow动员标记CX3CL1在S100A9-/-小鼠的滑膜中显著升高。接下来，我们研究了S100A8/A9对Ly6 Chigh单核细胞从骨髓释放到循环中的影响。在CIOAd7，WT BM的髓系细胞减少了14%。在S100A9-/-BM中未发现髓系细胞减少，提示S100A8/A9促进髓系细胞从骨髓中释放。局部诱导骨性关节炎导致S100A8/A9表达显著升高，Ly6Chigh单核细胞从骨髓进入滑膜的数量增加。本文的在线版本(doi：10.1186/s13075-017-1426-6)包含补充材料，授权用户可以使用。
Monocytes are dominant cells present within the inflamed synovium during osteoarthritis (OA). In mice, two functionally distinct monocyte subsets are described: pro-inflammatory Ly6Chigh and patrolling Ly6Clow monocytes. Alarmins S100A8/A9 locally released by the synovium during inflammatory OA for prolonged periods may be dominant proteins involved in stimulating recruitment of Ly6Chigh monocytes from the circulation to the joint. Our objective was to investigate the role of S100A8/A9 in the mobilization of Ly6Chigh and Ly6Clow monocytic populations to the inflamed joint in collagenase-induced OA (CiOA). S100A8 was injected intra-articularly to investigate monocyte influx. CiOA was induced by injection of collagenase into knee joints of wild-type C57BL/6 (WT), and S100a9-/- mice. Mice were sacrificed together with age-matched saline-injected control mice (n = 6/group), and expression of monocyte markers, pro-inflammatory cytokines, and chemokines was determined in the synovium using ELISA and RT-qPCR. Cells were isolated from the bone marrow (BM), spleen, blood, and synovium and monocytes were identified using FACS. S100A8/A9 was highly expressed during CiOA. Intra-articular injection of S100A8 leads to elevated expression of monocyte markers and the monocyte-attracting chemokines CCL2 and CX3CL1 in the synovium. At day 7 (d7) after CiOA induction in WT mice, numbers of Ly6Chigh, but not Ly6Clow monocytes, were strongly increased (7.6-fold) in the synovium compared to saline-injected controls. This coincided with strong upregulation of CCL2, which preferentially attracts Ly6Chigh monocytes. In contrast, S100a9-/- mice showed a significant increase in Ly6Clow monocytes (twofold) within the synovium at CiOA d7, whereas the number of Ly6Chigh monocytes remained unaffected. In agreement with this finding, the Ly6Clow mobilization marker CX3CL1 was significantly higher within the synovium of S100a9-/- mice. Next, we studied the effect of S100A8/A9 on release of Ly6Chigh monocytes from the BM into the circulation. A 14% decrease in myeloid cells was found in WT BM at CiOA d7. No decrease in myeloid cells in S100a9-/- BM was found, suggesting that S100A8/A9 promotes the release of myeloid populations from the BM. Induction of OA locally leads to strongly elevated S100A8/A9 expression and an elevated influx of Ly6Chigh monocytes from the BM to the synovium. The online version of this article (doi:10.1186/s13075-017-1426-6) contains supplementary material, which is available to authorized users.
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影响因子：
3.7
作者：
Jung H;Mithal DS;Park JE;Miller RJ
通讯作者：
Miller RJ
影响因子：
--
作者：
Bekkering, Siroon;Blok, Bastiaan A.;Netea, Mihai G.
通讯作者：
Netea, Mihai G.
DOI：
10.1165/rcmb.2016-0201oc
发表时间：
2017-05-01
影响因子：
6.4
作者：
Amsellem, Valerie;Abid, Shariq;Adnot, Serge
通讯作者：
Adnot, Serge
影响因子：
3.9
作者：
Cremers NA;Suttorp M;Gerritsen MM;Wong RJ;van Run-van Breda C;van Dam GM;Brouwer KM;Kuijpers-Jagtman AM;Carels CE;Lundvig DM;Wagener FA
通讯作者：
Wagener FA
影响因子：
--
作者：
Haywood, L;McWilliams, DF;Walsh, DA
通讯作者：
Walsh, DA