Yi Hyoju, Kang Kwi Young, Kim Youngkyun, Jung Hyerin, Rim Yeri Alice, Park Narae, Kim Juryun, Jung Seung Min, Park Sung-Hwan, Ju Ji Hyeon
CiSTEM Laboratory, Convergent Research Consortium for Immunologic Disease, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Division of Rheumatology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, 137-040, South Korea.
BMC Musculoskelet Disord. 2015 Jul 27;16:170. doi: 10.1186/s12891-015-0634-y.
Adipose-derived stem cells (ASCs) are mesenchymal stem cells (MSCs) derived from adipose tissue. MSCs have multiple properties including anti-inflammatory and immunomodulatory effects in various disease models and human diseases. However, the mechanisms underlying this wide range of effects need to be explored.
Collagen antibody-induced arthritis (CAIA) is a unique model in which arthritis is rapidly and strongly induced. ASCs were intraperitoneally infused into CAIA mice before or after arthritis induction. The serum levels of various cytokines, adipokines, and chemokines were measured. The expression of FC gamma receptors (FCGRs) was investigated in peritoneal macrophages ex vivo. RAW264.7 cells and ASCs were co-cultured to elucidate the direct and indirect role of ASCs on FCGR expression.
ASCs attenuated arthritis in CAIA mice. Serum levels of tumor necrosis factor α, interleukin (IL)-15, resistin, and leptin were reduced in ASC-treated CAIA mice, whereas serum levels of IL-6 and adiponectin were not affected. In peritoneal macrophages isolated from ASC-treated mice, expression of FCGRIIB, which is immunoinhibitory, was higher than that of FCGRI. Co-culture of ASCs with RAW264.7 cells modulated the expression of FCGRs. The expression patterns and timings of peak expression differed among FCGRs. Expression of FCGRIIB was higher and peaked earlier than that of FCGRI. FCGRIII expression was not affected by this co-culture.
This is a study to show that ASCs have anti-arthritic effects in CAIA mice. Modulation of FCGRs by ASCs might be a therapeutic mechanism in this antibody-associated arthritis model.
脂肪来源干细胞（ASCs）是源自脂肪组织的间充质干细胞（MSCs）。在各种疾病模型和人类疾病中，MSCs具有多种特性，包括抗炎和免疫调节作用。然而，这种广泛作用背后的机制仍有待探索。
胶原抗体诱导的关节炎（CAIA）是一种能快速强烈诱导关节炎的独特模型。在关节炎诱导之前或之后，将ASCs腹腔内注入CAIA小鼠。检测各种细胞因子、脂肪因子和趋化因子的血清水平。离体研究腹膜巨噬细胞中Fcγ受体（FCGRs）的表达。将RAW264.7细胞与ASCs共培养，以阐明ASCs对FCGR表达的直接和间接作用。
ASCs减轻了CAIA小鼠的关节炎。在接受ASC治疗的CAIA小鼠中，肿瘤坏死因子α、白细胞介素（IL）-15、抵抗素和瘦素的血清水平降低，而IL-6和脂联素的血清水平未受影响。在从接受ASC治疗的小鼠中分离出的腹膜巨噬细胞中，具有免疫抑制作用的FCGRIIB的表达高于FCGRI。ASCs与RAW264.7细胞共培养可调节FCGRs的表达。不同FCGRs的表达模式和表达峰值时间有所不同。FCGRIIB的表达更高且峰值出现得比FCGRI更早。FCGRIII的表达不受这种共培养的影响。
本研究表明ASCs在CAIA小鼠中具有抗关节炎作用。ASCs对FCGRs的调节可能是这种抗体相关关节炎模型中的一种治疗机制。
