Ren Guomin, Al-Jezani Nedaa, Railton Pamela, Powell James N, Krawetz Roman J
McCaig Institute for Bone & Joint Health, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, AB T2N 4N1, Canada.
University of Calgary, Biomedical Engineering Graduate Program, Calgary, AB T2N 4N1, Canada.
iScience. 2020 Dec 13;24(1):101943. doi: 10.1016/j.isci.2020.101943. eCollection 2021 Jan 22.
Synovitis is common in patients with osteoarthritis (OA) and is associated with pain and disease progression. We have previously demonstrated that the chemokine C-C motif chemokine 22 (CCL22) induces chondrocyte apoptosis however, the effects of CCL22 on the synovium remain unknown. Therefore, our goal was to investigate the effect of CCL22 on fibroblast-like synoviocytes (FLS). CCL22 treatment suppressed expression of IL-4 and IL-10 and promoted expression of S100A12 in FLS. The response of FLS to CCL22 was not dependent on the disease state of the joint (e.g., normal versus OA), but was instead correlated with the individuals' synovial fluid level of CCL22. CCL22 induction of S100A12 in FLS was attenuated after knockdown of CCR3, yet ligands of CCR3 (CCL7, CCL11) did not induce S100A12 expression. In the presence of CCL22, CCR3-positive FLS upregulate CCL22 and S100A12 driving a potential feedforward pro-inflammatory mechanism distinct from canonical CCL22 and CCR3 pathways.
滑膜炎在骨关节炎（OA）患者中很常见，且与疼痛和疾病进展相关。我们之前已证明趋化因子C-C基序趋化因子22（CCL22）可诱导软骨细胞凋亡，然而，CCL22对滑膜的影响仍不清楚。因此，我们的目标是研究CCL22对成纤维样滑膜细胞（FLS）的影响。CCL22处理抑制了FLS中IL-4和IL-10的表达，并促进了S100A12的表达。FLS对CCL22的反应不依赖于关节的疾病状态（如正常与OA），而是与个体滑膜液中CCL22的水平相关。在CCR3敲低后，CCL22诱导FLS中S100A12的作用减弱，然而CCR3的配体（CCL7、CCL11）并未诱导S100A12表达。在存在CCL22的情况下，CCR3阳性的FLS上调CCL22和S100A12，驱动一种不同于经典CCL22和CCR3途径的潜在前馈促炎机制。
