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支架蛋白 FKBP51 的分子形态关系与膝关节骨关节炎的炎症过程。

Molecular-Morphological Relationships of the Scaffold Protein FKBP51 and Inflammatory Processes in Knee Osteoarthritis.

机构信息

Laboratorio de Biología del Desarrollo, UD de Bioquímica y Biología Molecular Instituto de Tecnologías Biomédicas de Canarias, Universidad de La Laguna, La Laguna, Av. Astrofísico Sánchez s/n, 38206 La Laguna, Tenerife, Spain.

Orthopaedic Surgery and Trauma Unit, Royal Berkshire Hospital NHS Foundation Trust, Reading RG1 5AN, UK.

出版信息

Cells. 2021 Aug 25;10(9):2196. doi: 10.3390/cells10092196.

DOI:10.3390/cells10092196
PMID:34571845
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8468871/
Abstract

Knee osteoarthritis (OA) is one of the most prevalent chronic conditions affecting the adult population. OA is no longer thought to come from a purely biomechanical origin but rather one that has been increasingly recognized to include a persistent low-grade inflammatory component. Intra-articular corticosteroid injections (IACSI) have become a widely used method for treating pain in patients with OA as an effective symptomatic treatment. However, as the disease progresses, IACSI become ineffective. FKBP51 is a regulatory protein of the glucocorticoid receptor function and have been shown to be dysregulated in several pathological scenario's including chronic inflammation. Despite of these facts, to our knowledge, there are no previous studies of the expression and possible role of FKBP51 in OA. We investigated by double and triple immunofluorescence confocal microscopy the cellular and subcellular expression of FKBP51 and its relations with inflammation factors in osteoarthritic knee joint tissues: specifically, in the tibial plateau knee cartilage, Hoffa's fat pad and suprapatellar synovial tissue of the knee. Our results show co-expression of FKBP51 with TNF-α, IL-6, CD31 and CD34 in OA chondrocytes, synovial membrane cells and adipocytes in Hoffa's fat pad. FKBP51 is also abundant in nerve fibers within the fat pad. Co-expression of FKBP51 protein with these markers may be indicative of its contribution to inflammatory processes and associated chronic pain in OA.

摘要

膝骨关节炎(OA)是影响成年人群体最常见的慢性疾病之一。OA 不再被认为纯粹源于生物力学因素,而是越来越被认为包括持续低度炎症成分。关节内皮质类固醇注射(IACSI)已成为治疗 OA 患者疼痛的常用方法,作为一种有效的对症治疗。然而,随着疾病的进展,IACSI 变得无效。FKBP51 是糖皮质激素受体功能的调节蛋白,在包括慢性炎症在内的几种病理情况下已被证明失调。尽管有这些事实,但据我们所知,以前没有研究过 FKBP51 在 OA 中的表达及其可能的作用。我们通过双免疫荧光和三重免疫荧光共聚焦显微镜研究了 FKBP51 的细胞和亚细胞表达及其与膝关节炎关节组织中炎症因子的关系:具体来说,在胫骨平台膝关节软骨、Hoffa 脂肪垫和髌上滑膜组织中。我们的结果表明,FKBP51 与 TNF-α、IL-6、CD31 和 CD34 在 OA 软骨细胞、滑膜膜细胞和 Hoffa 脂肪垫中的脂肪细胞中表达共定位。FKBP51 在脂肪垫内的神经纤维中也很丰富。FKBP51 蛋白与这些标志物的共表达可能表明其参与了 OA 中的炎症过程和相关的慢性疼痛。

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