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聚集蛋白聚糖酶特异性抑制剂减少 ARGS-聚集蛋白聚糖释放 在关节不稳的大鼠半月板撕裂模型中

发布者:抗性基因网 时间:2021-09-18 浏览量:674

摘要

       骨关节炎 (OA) 是最常见的关节炎形式,影响在美国有近 2700 万人。 OA造成的损失由于蛋白水解酶的产生增加,关节软骨如基质金属蛋白酶 (MMP) 和蛋白聚糖酶。我们有先前报道了敏感和
定量 ELISA 以测量 ARGS-聚集蛋白聚糖 (1),一种主要的通过特定的聚集蛋白聚糖酶活性在关节中产生的聚集蛋白聚糖片段并释放到滑液 (SF) 中。在这项研究中,我们调查了大鼠半月板撕裂中 ARGS-聚集蛋白聚糖的时间依赖性释放(MT) 手术引起的关节不稳定后的关节损伤模型。此外,我们评估了口服给药的效果大鼠 MT 模型中的聚集蛋白聚糖酶特异性抑制剂 (ASI);相同我们之前已经证明聚集蛋白聚糖酶特异性抑制剂导致组织学软骨保护和疾病改变以与当前研究相似的剂量测试大鼠模型 (2)。现在的研究结果验证了 ARGS-蛋白聚糖 ELISA 作为关节疾病的生物标志物损伤并支持蛋白聚糖酶抑制剂的开发关节损伤的潜在治疗方法。

       Osteoarthritis (OA) is the most common form of arthritis, affecting nearly 27 million people in the United States. The loss caused by OA is due to the increased production of proteolytic enzymes, articular cartilage such as matrix metalloproteinase (MMP) and proteoglycanase. We have previously reported sensitive and
Quantitative ELISA to measure ARGS-agrecan (1), a type of aggrecan fragment mainly produced in joints by specific aggrecanase activity and released into synovial fluid (SF). In this study, we investigated the time-dependent release of ARGS-agrecan in a rat meniscus tear (MT) in a joint injury model following joint instability caused by surgery. In addition, we evaluated the effects of oral administration of aggrecanase-specific inhibitors (ASI) in the rat MT model; similarly, we have previously demonstrated that aggrecanase-specific inhibitors lead to histological chondroprotection and disease The rat model was tested at a dose similar to the current study (2). The current research results validate the ARGS-proteoglycan ELISA as a biomarker of joint disease damage and support the development of proteoglycanase inhibitors as a potential treatment for joint damage.

http://www.ors.org/Transactions/56/0302.pdf