Anti-catabolic effect of OP-1 in chronically compressed intervertebral discs
Anti-catabolic effect of OP-1 in chronically compressed intervertebral discs
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DOI：
10.1002/jor.20339
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发表时间：
2007-04-01
影响因子：
2.8
通讯作者：
Rueger, David C.
中科院分区：
文献类型：
--
作者：
Chubinskaya, Susan;Kawakami, Mamoru;Rueger, David C.
椎间盘退变的实验动物模型已被用于评估椎间盘的生物力学行为、生物化学组成和生物学变化。本研究的目的是通过组织学和免疫组织化学方法评价椎间盘内注射成骨蛋白-1（OP-1）对椎间盘退变模型的合成代谢和抗分解代谢作用。将34只大鼠分为5组：完整对照组;假手术对照组;注射生理盐水的压缩髓核（NP）组;以及两个OP-1组：COP-1组（椎间盘内注射OP-1后继续压缩）和ROP-1组（在注射OP-1时释放压缩）。OP-1的合成代谢和抗分解代谢作用通过组织学和免疫组织化学用以下抗体进行评价：抗前成熟OP-1和抗成熟OP-1、抗XIMP-13、抗聚集蛋白聚糖酶、抗P物质、抗肿瘤坏死因子-α（TNF-α）和抗白细胞介素-1 β（IL-1 β）。向退行性椎间盘注射OP-1刺激合成代谢反应，其特征在于恢复椎间盘的正常形态，NP中番红0染色增加，细胞外基质延伸，以及刺激NP、纤维环（AF）和终板中内源性OP-1合成。OP-1的抗分解代谢作用通过减少聚集蛋白聚糖酶、MMP-13、P物质、TNF-α和IL-1 β的免疫染色来证明。这项研究证实了OP-1的抗分解代谢活性，如先前在人关节软骨中所证明的，并为OP-1治疗椎间盘退变的潜力提供了关键证据。由于P物质是一种与炎症和疼痛相关的神经肽，这种蛋白质水平的降低可能支持我们先前报道的OP-1对疼痛相关行为影响的结果。(c)2007骨科研究学会。出版社：Wiley Periodicals，Inc.
Experimental animal models of disc degeneration have been used to assess the biomechanical behavior, biochemical composition, and biological changes in the intervertebral discs. The objective of our study was to evaluate the anabolic and anti-catabolic effects of intradiscal injection of Osteogenic Protein-1 (OP-1) by histology and immunohistochemistry in disc degeneration model. Thirty-four rats were divided into five groups: intact control; sham control; compressed nucleus pulposus (NP) injected with saline; and two OP-1 groups: COP-1 group (compression was continued after intradiscal OP-1 injection) and ROP-1 group (compression was released at the time of OP-1 injection). Anabolic and anti-catabolic effects of OP-1 were evaluated by histology and immunohistochemistry with the following antibodies: anti-pro- and anti-mature OP-1, anti-XIMP-13, anti-aggrecanase, anti-substance P, anti-tumor necrosis factor-alpha (TNF-alpha), and anti-interleukin-1 beta (IL-1 beta). The OP-1 injection to the degenerative disc stimulated an anabolic response characterized by the restoration of the normal morphology of the disc, increased Safranin 0 staining in the NP, extention of the extracellular matrix, and stimulation of endogenous OP-1 synthesis in the NP, annulus fibrosis (AF), and end-plate. The anti-catabolic effect of OP-1 was documented by reduced immunostaining for aggrecanase, MMP-13, substance P, TNF-alpha, and IL-1 beta. This study confirmed the anti-catabolic activity of OP-1 as demonstrated previously in human articular cartilage and provided critical evidence for the potential of OP-1 therapy in the treatment of disc degeneration. Because substance P is a neuropeptide linked with inflammation and pain, a reduction in the level of this protein may support our previously reported results on the effect of OP-1 on pain-related behavior. (c) 2007 Orthopaedic Research Society. Published byWiley Periodicals, Inc.