糖尿病相关性骨关节炎滑膜组织硫化氢生物合成及其对巨噬细胞表型和丰度影响的研究。

IF 3.7 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Natalia Lendoiro-Cino, Arianna Rodríguez-Coello, Anna Saborido, Elena F-Burguera, Jennifer A Fernández-Rodríguez, Rosa Meijide-Faílde, Francisco J Blanco, Carlos Vaamonde-García
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引用次数: 0

摘要

2型糖尿病(DB)是骨关节炎(OA)的独立危险因素。然而,这两种疾病之间联系的机制尚不清楚。OA合并DB患者的滑膜巨噬细胞表现出明显的促炎表型。由于硫化氢(H2S)先前已被描述参与巨噬细胞极化,在本研究中,我们检查了OA伴DB患者滑膜组织中H2S的生物合成,观察到这部分个体中H2S合成酶的减少。为了阐明这些发现,我们检测到,暴露于高水平葡萄糖的巨噬细胞分化的TPH-1细胞表现出h2s合成酶的低表达和对LPS的炎症反应增加,与M1表型相关的标志物(即CD11c、CD86、iNOS和IL-6)的表达上调,与M2命运相关的标志物(CD206和CD163)的表达降低。细胞与缓释H2S供体GYY-4137共处理,降低了M1标记物的表达,但未能调节M2指标的水平。GYY-4137还降低了HIF-1α的表达,上调了HO-1的蛋白水平,表明它们参与了H2S诱导的抗炎作用。此外,我们在OA体内模型中观察到,在关节内给药H2S降低了滑膜中CD68+细胞(主要是巨噬细胞)的丰度。综上所述,本研究的发现似乎强化了H2S在与OA相关的滑膜巨噬细胞m1样极化中的关键作用,特别是其代谢表型,为该病理的治疗开辟了新的治疗视角。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Study of hydrogen sulfide biosynthesis in synovial tissue from diabetes-associated osteoarthritis and its influence on macrophage phenotype and abundance.

Study of hydrogen sulfide biosynthesis in synovial tissue from diabetes-associated osteoarthritis and its influence on macrophage phenotype and abundance.

Type 2 diabetes (DB) is an independent risk factor for osteoarthritis (OA). However, the mechanisms underlying the connection between both diseases remain unclear. Synovial macrophages from OA patients with DB present a marked pro-inflammatory phenotype. Since hydrogen sulphide (H2S) has been previously described to be involved in macrophage polarization, in this study we examined H2S biosynthesis in synovial tissue from OA patients with DB, observing a reduction of H2S-synthetizing enzymes in this subset of individuals. To elucidate these findings, we detected that differentiated TPH-1 cells to macrophages exposed to high levels of glucose presented a lower expression of H2S-synthetizing enzymes and an increased inflammatory response to LPS, showing upregulated expression of markers associated with M1 phenotype (i.e., CD11c, CD86, iNOS, and IL-6) and reduced levels of those related to M2 fate (CD206 and CD163). The co-treatment of the cells with a slow-releasing H2S donor, GYY-4137, attenuated the expression of M1 markers, but failed to modulate the levels of M2 indicators. GYY-4137 also reduced HIF-1α expression and upregulated the protein levels of HO-1, suggesting their involvement in the anti-inflammatory effects of H2S induction. In addition, we observed that intraarticular administration of H2S donor attenuated synovial abundance of CD68+ cells, mainly macrophages, in an in vivo model of OA. Taken together, the findings of this study seem to reinforce the key role of H2S in the M1-like polarization of synovial macrophages associated to OA and specifically its metabolic phenotype, opening new therapeutic perspectives in the management of this pathology.

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来源期刊
Journal of physiology and biochemistry
Journal of physiology and biochemistry 生物-生化与分子生物学
CiteScore
6.60
自引率
0.00%
发文量
86
审稿时长
6-12 weeks
期刊介绍: The Journal of Physiology and Biochemistry publishes original research articles and reviews describing relevant new observations on molecular, biochemical and cellular mechanisms involved in human physiology. All areas of the physiology are covered. Special emphasis is placed on the integration of those levels in the whole-organism. The Journal of Physiology and Biochemistry also welcomes articles on molecular nutrition and metabolism studies, and works related to the genomic or proteomic bases of the physiological functions. Descriptive manuscripts about physiological/biochemical processes or clinical manuscripts will not be considered. The journal will not accept manuscripts testing effects of animal or plant extracts.
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