Laboratory for Experimental Orthopedics, Department of Orthopaedic Surgery, Maastricht University Medical Centre +, Maastricht, The Netherlands.
Laboratory for Experimental Orthopedics, Department of Orthopaedic Surgery, Maastricht University Medical Centre +, Maastricht, The Netherlands.
Osteoarthritis Cartilage. 2018 May;26(5):697-706. doi: 10.1016/j.joca.2018.01.025. Epub 2018 Feb 7.
The Hoffa's fat pad (HFP) is an intra-articular adipose tissue which is situated under and behind the patella. It contains immune cells next to adipocytes and secretes inflammatory factors during osteoarthritis (OA). In this study, we compared the release profile of prostanoids, which are involved in inflammation, of HFP from OA patients vs patients with a focal cartilage defect (CD) without evidence for OA on MRI and investigated the prostanoid modulatory anti-inflammatory action of celecoxib on HFP.
Prostanoid release was analyzed in conditioned medium of HFP explant cultures from 17 osteoarthritic patients and 12 CD patients, in the presence or absence of celecoxib. Furthermore, gene expression of COX enzymes and expression of genes indicative of a pro-inflammatory or anti-inflammatory phenotype of HFP was analyzed.
Prostanoid release by HFP from knee OA patients clustered in two subgroups with high and low prostanoid producers. HFP from high prostanoid producers released higher amounts of PGE, PGF and PGD compared to HFP from CD patients. PGE release by OA HFP was positively associated with expression of genes known to be expressed by M1 macrophages, indicating a role for macrophages. Celecoxib modulated prostanoid release by HFP, and also modulated the inflammation ratio towards a more favorable anti-inflammatory M2 phenotype, most effectively in patients with higher prostanoid release profiles.
In knee OA patients with inflamed HFP's, celecoxib may exert positive effects in the knee joint via decreasing the release of prostanoids produced by the HFP and by favorably modulating the anti-inflammatory marker expression in HFP.
Hoffa 脂肪垫（HFP）是位于髌骨下方和后方的关节内脂肪组织。它含有紧邻脂肪细胞的免疫细胞，并在骨关节炎（OA）期间分泌炎症因子。在这项研究中，我们比较了 OA 患者和 MRI 无 OA 证据的局灶性软骨缺损（CD）患者的 HFP 中参与炎症的前列腺素释放谱，并研究了塞来昔布对 HFP 前列腺素调节抗炎作用。
在存在或不存在塞来昔布的情况下，分析了 17 名骨关节炎患者和 12 名 CD 患者的 HFP 组织块培养物条件培养基中的前列腺素释放情况。此外，还分析了 COX 酶的基因表达和 HFP 促炎或抗炎表型的基因表达。
OA 患者的 HFP 前列腺素释放可分为高和低前列腺素产生者两个亚群。与 CD 患者相比，高前列腺素产生者的 HFP 释放出更高水平的 PGE、PGF 和 PGD。OA HFP 的 PGE 释放与已知由 M1 巨噬细胞表达的基因表达呈正相关，表明巨噬细胞的作用。塞来昔布调节 HFP 的前列腺素释放，并使炎症比率向更有利的抗炎 M2 表型调节，在前列腺素释放谱较高的患者中效果最佳。
在有炎症性 HFP 的膝骨关节炎患者中，塞来昔布可能通过减少 HFP 产生的前列腺素的释放，并通过有利地调节 HFP 中的抗炎标志物表达，在膝关节中发挥积极作用。
