Aberrant Expression of COX-2 and FOXG1 in Infrapatellar Fat Pad-Derived ASCs from Pre-Diabetic Donors.
Aberrant Expression of COX-2 and FOXG1 in Infrapatellar Fat Pad-Derived ASCs from Pre-Diabetic Donors.
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糖尿病前期供者髌骨脂肪垫来源的ASCs中考克斯-2和FOXG 1的异常表达
作者：
骨关节炎（OA）是一种退行性关节疾病，导致活动受限和严重残疾。2型糖尿病（T2D）是OA的一个体重无关的危险因素，但两种疾病之间的联系尚未阐明。从髌下脂肪垫（IPFP）中分离的脂肪干细胞（ASCs）可能是OA治疗中可行的再生细胞。本研究分析了非糖尿病（Non-T2D）、糖尿病前期（Pre-T2D）和T2D供者IPFP-ASCs中炎症和脂肪因子相关基因的表达谱。与非T2D和T2D IPFP-ASCs相比，T2D前的ASCs表现出间充质标志物CD90和CD105水平的显著下降，而成脂分化没有变化。此外，在白细胞介素-1β (IL-1β)刺激下，Pre-T2D IPFP-ASCs中环氧化酶-2 （COX-2）、叉头盒G1 （FOXG1）表达和前列腺素E2 （PGE2）分泌显著增加。有趣的是，当M1巨噬细胞与Pre-T2D IPFP-ASCs共培养时，促炎标志物TNFα和IL-6的表达显著降低。这些数据表明，未经治疗的T2D相关的全身性炎症升高可能通过抑制IL-6/COX-2信号通路，使IPFP-ASCs表现出增强的抗炎特性。此外，t2d前IPFP-ASCs产生的PGE2升高也可能提示糖尿病前期状况对OA的发生和进展的贡献。
Osteoarthritis (OA) is a degenerative joint disease resulting in limited mobility and severe disability. Type II diabetes mellitus (T2D) is a weight-independent risk factor for OA, but a link between the two diseases has not been elucidated. Adipose stem cells (ASCs) isolated from the infrapatellar fat pad (IPFP) may be a viable regenerative cell for OA treatment. This study analyzed the expression profiles of inflammatory and adipokine-related genes in IPFP-ASCs of non-diabetic (Non-T2D), pre-diabetic (Pre-T2D), and T2D donors. Pre-T2D ASCs exhibited a substantial decrease in levels of mesenchymal markers CD90 and CD105 with no change in adipogenic differentiation compared to Non-T2D and T2D IPFP-ASCs. In addition, Cyclooxygenase-2 (COX-2), Forkhead box G1 (FOXG1) expression and prostaglandin E2 (PGE2) secretion were significantly increased in Pre-T2D IPFP-ASCs upon stimulation by interleukin-1 beta (IL-1β). Interestingly, M1 macrophages exhibited a significant reduction in expression of pro-inflammatory markers TNFα and IL-6 when co-cultured with Pre-T2D IPFP-ASCs. These data suggest that the heightened systemic inflammation associated with untreated T2D may prime the IPFP-ASCs to exhibit enhanced anti-inflammatory characteristics via suppressing the IL-6/COX-2 signaling pathway. In addition, the elevated production of PGE2 by the Pre-T2D IPFP-ASCs may also suggest the contribution of pre-diabetic conditions to the onset and progression of OA.
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