Intradiscal administration of osteogenic protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits
Intradiscal administration of osteogenic protein-1 increases intervertebral disc height and proteoglycan content in the nucleus pulposus in normal adolescent rabbits
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DOI：
10.1097/01.brs.0000148002.68656.4d
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发表时间：
2005-01-01
期刊：
影响因子：
3
通讯作者：
Masuda, K
中科院分区：
文献类型：
--
作者：
An, HS;Takegami, K;Masuda, K
研究设计。兔髓核注射成骨蛋白-1后椎间盘高度及生化变化的研究。目的观察成骨蛋白-1在兔椎间盘内注射的体内作用。背景资料摘要。生长因子，如成骨蛋白-1和转化生长因子- β，在体外具有刺激蛋白聚糖和胶原蛋白合成的能力。目前还没有人尝试在体内模型中确定这些生长因子的作用。将24只新西兰青春期大白兔平均分为两组。一组连续3个椎间盘注射生理盐水；而另一组则在生理盐水中注射成骨蛋白-1。在注射后2、4和8周，通过侧位平片测量注射标本的椎间盘高度，并与注射前的测量结果进行比较。椎间盘高度的变化表示为椎间盘高度指数与注射前值相比的百分比。获得影像学测量结果后，取出椎间盘，分析DNA、蛋白多糖和胶原蛋白含量。注射后2周，成骨蛋白-1组椎间盘的平均高度指数比生理盐水组高15%。在第4周和第8周时间点，成骨蛋白-1注射后椎间盘高度的增加仍有统计学意义。在2周时间点，成骨蛋白-1注射组椎间盘髓核蛋白多糖含量明显高于生理盐水组。成骨蛋白1对蛋白多糖含量的影响在4周和8周的时间间隔内也存在；然而，这些增长在统计上并不显著。生理盐水组和成骨蛋白-1组的髓核DNA含量与未注射对照组相比无显著差异。4周后，与生理盐水组相比，成骨蛋白-1组纤维环DNA含量明显升高。到目前为止，还没有研究证明生长因子对椎间盘的潜在体内影响。本研究报道，在体内椎间盘内给药成骨蛋白-1导致椎间盘高度在2周、4周和8周时增加，2周时髓核PG含量增加。因此，成骨蛋白-1可能刺激髓核的代谢活动。在合适的动物模型中，生长因子诱导的年龄相关性椎间盘退变逆转的潜力需要继续的研究来评估。此外，在考虑在人类椎间盘内注射生长因子之前，非人类灵长类动物模型的研究将是必不可少的。
Study Design. A study of the disc height and biochemical changes in the rabbit intervertebral disc after injection of osteogenic protein-1 into the nucleus pulposus.Objectives. To evaluate the in vivo effects of osteogenic protein-1 administered intradiscally to the intervertebral disc of rabbits.Summary of Background Data. Growth factors, such as osteogenic protein-1 and transforming growth factor-beta, have the ability to stimulate synthesis of proteoglycan and collagen in vitro. No attempts have yet been made to determine the effects of these growth factors in an in vivo model.Methods. Twenty-four New Zealand adolescent white rabbits were divided evenly into two subject groups. In one group, three consecutive intervertebral discs were injected with saline; whereas in the other group, they were injected with osteogenic protein-1 in saline. At 2, 4, and 8 weeks after the injection, the intervertebral disc heights of the injected specimens were measured by lateral plain radiographs and compared with preinjection measurements. The change in disc height was expressed as the percent disc height index compared with the preinjection value. After the radiographic measurements were obtained, the intervertebral discs were removed and analyzed for DNA, proteoglycan, and collagen contents.Results. At 2 weeks after the injections, the mean disc height index of the osteogenic protein-1-injected discs was 15% greater than that of the saline group. The increase in disc height with osteogenic protein-1 injection was still statistically significant at the 4- and 8-week time points. The proteoglycan content of the nucleus pulposus in discs injected with osteogenic protein-1 was higher than that in the saline group at the 2-week time point. The osteogenic protein-1-induced effect on the proteoglycan content was also present at the 4- and 8-week time intervals; however, these increases were not statistically significant. There were no significant differences in the DNA content, normalized to noninjected control, of the nucleus pulposus between the saline and osteogenic protein-1 groups. However, a significant increase in the DNA content of the anulus fibrosus in the osteogenic protein-1 group, compared with that of the anulus fibrosus in the saline group, was observed after 4 weeks.Conclusion. To date, no study has demonstrated the potential in vivo effects of growth factors on the intervertebral disc. The present study reports that the intradiscal administration of osteogenic protein-1 in vivo results in an increased disc height present at 2, 4, and 8 weeks and an increase in PG content of the nucleus pulposus at the 2-week time point. Therefore, osteogenic protein-1 may act to stimulate metabolic activity in the nucleus pulposus. Continued research is needed to evaluate the potential of growth factor-induced reversal of age-related disc degeneration in an appropriate animal model. In addition, studies in a nonhuman primate animal model will be essential before considering intradiscal injection of growth factors in humans.