1 Department of Orthopaedics, University Medical Center Utrecht, Utrecht, The Netherlands.
2 Department of Rheumatology and Clinical Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Cartilage. 2019 Jul;10(3):329-334. doi: 10.1177/1947603518754629. Epub 2018 Jan 24.
Fibulin-3 is a glycoprotein highly expressed in osteoarthritic cartilage and inhibits angiogenesis and chondrocyte differentiation. Recent studies have indicated that fibulin-3 has potential value as a biomarker in osteoarthritis. The aim of the present study is to examine the role of 3 fibulin-3 peptides (Fib3-1, Fib3-2, and Fib3-3) and a type II collagen degradation product in a rat osteoarthritis model with systemic metabolic alterations combined with local cartilage damage.
Forty, 12-week-old male, Wistar rats were randomly divided over 2 groups: a standard or a high-fat diet inducing metabolic dysregulation. After 12 weeks, articular cartilage damage was induced on the femoral condyles (groove model), in 1 knee joint in 14 rats of each diet group. At endpoint, blood was collected and serum was isolated. Enzyme-linked immunosorbent assay on all selected fibulin-3 fragments was performed from serum samples in addition to immunohistochemical analysis for Fib3-3.
Serum concentrations of Fib3-3 were increased by 29.9%, when cartilage damage was induced in addition to a high-fat diet. Fib3-3 was also associated with an increased histological total joint degeneration ( = 0.435) and cartilage degeneration ( = 0.435). Immunostainings demonstrated increased Fib3-3 in the superficial cartilage of animals with high-fat diet and/or cartilage damage.
In the rat groove model combined with high-fat diet-induced metabolic dysregulation an increased Fib3-3 concentration was observed systemically, which is associated with local joint degeneration. This suggests that systemic Fib3-3 concentrations can indicate the status of joint degeneration and function as a biomarker in osteoarthritis.
纤连蛋白 3 是一种在骨关节炎软骨中高度表达的糖蛋白,可抑制血管生成和软骨细胞分化。最近的研究表明,纤连蛋白 3 作为骨关节炎的生物标志物具有潜在价值。本研究旨在探讨 3 种纤连蛋白 3 肽(Fib3-1、Fib3-2 和 Fib3-3)和一种 II 型胶原降解产物在伴有全身代谢改变和局部软骨损伤的大鼠骨关节炎模型中的作用。
40 只 12 周龄雄性 Wistar 大鼠随机分为 2 组:标准饮食组或高脂饮食组诱导代谢紊乱。12 周后,在每个饮食组的 14 只大鼠的 1 个膝关节的股骨髁上造成关节软骨损伤(沟槽模型)。在终点时,采集血液并分离血清。除了对 Fib3-3 进行免疫组织化学分析外,还对所有选定的纤连蛋白 3 片段的血清样本进行酶联免疫吸附试验。
在高脂饮食加软骨损伤的情况下,血清 Fib3-3 浓度增加了 29.9%。Fib3-3 还与组织学总关节退变(=0.435)和软骨退变(=0.435)增加相关。免疫染色显示高脂饮食和/或软骨损伤动物的浅表层软骨中 Fib3-3 增加。
在大鼠沟槽模型结合高脂饮食诱导的代谢紊乱中,全身性观察到 Fib3-3 浓度增加,与局部关节退变相关。这表明系统 Fib3-3 浓度可以指示关节退变的状态,并作为骨关节炎的生物标志物。