Prevention of Cartilage Degeneration in a Rat Model of Osteoarthritis by Intraarticular Treatment With Recombinant Lubricin
Prevention of Cartilage Degeneration in a Rat Model of Osteoarthritis by Intraarticular Treatment With Recombinant Lubricin
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DOI：
10.1002/art.24304
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发表时间：
2009-03-01
影响因子：
--
通讯作者：
Glasson, Sonya S.
中科院分区：
文献类型：
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作者：
Flannery, Carl R.;Zollner, Richard;Glasson, Sonya S.
Objective. Lubricin，也称为表浅区蛋白和PRG4，是一种滑膜糖蛋白，其为关节软骨表面提供抗摩擦、抗粘附涂层，从而防止关节炎相关组织磨损和降解。本研究旨在产生和表征一种新型重组润滑素蛋白构建体LUB：1，并评估其在大鼠骨关节炎（OA）模型中关节内递送后的治疗效果。通过免疫组织化学评估LUB：1与软骨表面的结合和定位。使用定制摩擦测试装置测定LUB：1的软骨润滑性能。进行细胞结合测定以定量LUB：1防止细胞粘附的能力。在OA的大鼠结膜撕裂模型中进行功效研究。手术诱导OA后1周，通过关节内注射给予LUB：1或磷酸盐缓冲盐水溶媒，持续4周，给药间隔为每周1次或每周3次。通过组织学分析确定OA病理评分。LUB：1显示有效地结合软骨表面，并且促进软骨边界润滑和抑制滑膜细胞粘附。用LUB：1治疗大鼠膝关节，通过显著减少软骨退变和结构损伤，在OA进展过程中产生显著的疾病改善和软骨保护作用。我们的研究结果表明重组润滑素分子在治疗OA和相关软骨异常的新型生物治疗方法中的潜在用途。
Objective. Lubricin, also referred to as superficial zone protein and PRG4, is a synovial glycoprotein that supplies a friction-resistant, antiadhesive coating to the surfaces of articular cartilage, thereby protecting against arthritis-associated tissue wear and degradation. This study was undertaken to generate and characterize a novel recombinant lubricin protein construct, LUB:1, and to evaluate its therapeutic efficacy following intraarticular delivery in a rat model of osteoarthritis (OA).Methods. Binding and localization of LUB:1 to cartilage surfaces was assessed by immunohistochemistry. The cartilage-lubricating properties of LUB:1 were determined using a custom friction testing apparatus. A cell-binding assay was performed to quantify the ability of LUB:1 to prevent cell adhesion. Efficacy studies were conducted in a rat meniscal tear model of OA. One week after the surgical induction of OA, LUB:1 or phosphate buffered saline vehicle was administered by intraarticular injection for 4 weeks, with dosing intervals of either once per week or 3 times per week. OA pathology scores were determined by histologic analysis.Results. LUB:1 was shown to bind effectively to cartilage surfaces, and facilitated both cartilage boundary lubrication and inhibition of synovial cell adhesion. Treatment of rat knee joints with LUB:1 resulted in significant disease-modifying, chondroprotective effects during the progression of OA, by markedly reducing cartilage degeneration and structural damage.Conclusion. Our findings demonstrate the potential use of recombinant lubricin molecules in novel biotherapeutic approaches to the treatment of OA and associated cartilage abnormalities.