BMP-7 Protects against Progression of Cartilage Degeneration after Impact Injury
BMP-7 Protects against Progression of Cartilage Degeneration after Impact Injury
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DOI：
10.1002/jor.20787
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发表时间：
2009-05-01
影响因子：
2.8
通讯作者：
Rueger, David
中科院分区：
文献类型：
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作者：
Hurtig, Mark;Chubinskaya, Susan;Rueger, David
体内研究用于表征导致绵羊内侧股胫关节骨关节炎进展的软骨损伤模型。在随后的三项研究中，造成双侧撞击损伤，一个关节接受关节内注射340 μ g胶原颗粒载体中的rhBMP-7蛋白，而对侧膝关节仅接受载体。将绵羊分为三组，分别在实验性膝关节损伤后第0天（A组）、第21天（B组）或第90天（C组）接受关节内注射。在每组中，在最后一次治疗后90天，使用印度墨水染色面积、OARSI组织学评分、软骨sGAG含量、细胞凋亡免疫染色（TUNEL）、半胱天冬酶-3、胶原降解（Col 2 3/4C短胶原表位）和内源性BMP-7蛋白（原）形式，评价关节骨关节炎进展的体征。在损伤后立即接受rhBMP-7的膝关节在损伤部位有小的局部损伤，这些损伤没有进展到周围的软骨。在损伤后3周接受BMP-7的关节没有得到证实，与对照组相比进展有限，但在损伤后12周接受蛋白质的关节没有统计学显著改善。这些研究表明，如果在指数损伤的3至4周内施用BMP-7，则BMP-7可能在患者的创伤性损伤后具有软骨保护作用。亚致死损伤后的保护机制似乎是能够参与修复过程的软骨细胞的存活增加。(C)2008骨科研究学会。出版社：Wiley Periodicals，Inc. J Orthop Res 27：602-611，2009
In vivo studies were used to characterize a model of cartilage injury leading to osteoarthritis progression in the medial femorotibial joint of sheep. In three subsequent studies, bilateral impact injuries were created and one joint received intraarticular injections of 340 mu g of rhBMP-7 protein in a collagen particle carrier while the contralateral knee received the vehicle alone. Sheep were allocated to three groups that received intraarticular injections on day 0 (group A), 21 (group B), or 90 (group C) after experimental knee injury. In each group the, joints were evaluated for signs of osteoarthritis progression 90 days after the last treatment, using India ink stained area, OARSI histological scoring, cartilage sGAG content, immunostaining for apoptosis (TUNEL), caspase-3, collagen degradation (Col 2 3/4C short collagen epitope), and the endogenous, (pro-) form of BMP-7 protein. Knee joints that received rhBMP-7 immediately after injury had small local lesions at the injury site that did not progress into the surrounding cartilage. Joints that received BMP-7 3 weeks after injury were unproved and had limited progression compared to control, but joints that received the protein 12 weeks after injury had no statistically significant improvement. These studies suggest that BMP-7 may be chondroprotective after traumatic injury in patients if it is administered within 3 to 4 weeks of the index injury. The mechanism of protection after sublethal injury appeared to be an increased survival of chondrocytes that are able to participate in the repair process. (C) 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:602-611, 2009