Silverstein A M, Stefani R M, Sobczak E, Tong E L, Attur M G, Shah R P, Bulinski J C, Ateshian G A, Hung C T
Department of Biomedical Engineering, Columbia University, New York, NY, USA.
Division of Rheumatology, Department of Medicine, New York University School of Medicine and NYU Langone Medical Center, New York, NY, USA.
Osteoarthritis Cartilage. 2017 Aug;25(8):1353-1361. doi: 10.1016/j.joca.2017.03.015. Epub 2017 Mar 30.
Arthroscopy with lavage and synovectomy can remove tissue debris from the joint space and the synovial lining to provide pain relief to patients with osteoarthritis (OA). Here, we developed an in vitro model to study the interaction of cartilage wear particles with fibroblast-like synoviocytes (FLS) to better understand the interplay of cartilage particulates with cytokines on cells of the synovium.
In this study sub-10 μm cartilage particles or 1 μm latex particles were co-cultured with FLS ±10 ng/mL interleukin-1α (IL-1α) or tumor necrosis factor-α (TNF-α). Samples were analyzed for DNA, glycosaminoglycan (GAG), and collagen, and media samples were analyzed for media GAG, nitric oxide (NO) and prostaglandin-E2 (PGE2). The nature of the physical interaction between the particles and FLS was determined by microscopy.
Both latex and cartilage particles could be phagocytosed by FLS. Cartilage particles were internalized and attached to the surface of both dense monolayers and individual cells. Co-culture of FLS with cartilage particulates resulted in a significant increase in cell sheet DNA and collagen content as well as NO and PGE2 synthesis compared to control and latex treated groups.
The proliferative response of FLS to cartilage wear particles resulted in an overall increase in extracellular matrix (ECM) content, analogous to the thickening of the synovial lining observed in OA patients. Understanding how cartilage particles interface with the synovium may provide insight into how this interaction contributes to OA progression and may guide the role of lavage and synovectomy for degenerative disease.
关节镜下灌洗和滑膜切除术可清除关节间隙和滑膜衬里的组织碎片,为骨关节炎(OA)患者缓解疼痛。在此,我们建立了一个体外模型,以研究软骨磨损颗粒与成纤维样滑膜细胞(FLS)的相互作用,从而更好地理解软骨微粒与细胞因子在滑膜细胞上的相互作用。
在本研究中,将小于10μm的软骨颗粒或1μm的乳胶颗粒与FLS共同培养,并添加或不添加10ng/mL白细胞介素-1α(IL-1α)或肿瘤坏死因子-α(TNF-α)。对样本进行DNA、糖胺聚糖(GAG)和胶原蛋白分析,对培养基样本进行培养基GAG、一氧化氮(NO)和前列腺素-E2(PGE2)分析。通过显微镜确定颗粒与FLS之间物理相互作用的性质。
乳胶颗粒和软骨颗粒均可被FLS吞噬。软骨颗粒被内化并附着在致密单层细胞和单个细胞的表面。与对照组和乳胶处理组相比,FLS与软骨微粒共同培养导致细胞片层DNA和胶原蛋白含量以及NO和PGE2合成显著增加。
FLS对软骨磨损颗粒的增殖反应导致细胞外基质(ECM)含量总体增加,类似于OA患者滑膜衬里增厚的情况。了解软骨颗粒与滑膜的相互作用方式,可能有助于深入了解这种相互作用如何促进OA进展,并可能指导灌洗和滑膜切除术在退行性疾病中的作用。