Gene expression for type-specific collagens in osteogenic protein-1 (rhBMP-7)-induced lumbar intertransverse process fusion in rabbits
Gene expression for type-specific collagens in osteogenic protein-1 (rhBMP-7)-induced lumbar intertransverse process fusion in rabbits
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DOI：
10.1080/03008200600978292
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发表时间：
2006-10-01
影响因子：
2.9
通讯作者：
Moriya, Hideshige
中科院分区：
文献类型：
--
作者：
Hisamitsu, Junshiro;Yamazaki, Masashi;Moriya, Hideshige
为了阐明成骨蛋白（OP）-1诱导腰椎后外侧融合（PLF）的分子机制，我们采用原位杂交（ISH）技术分析了OP-1诱导兔PLF的过程。使用OP-1（n = 18）或单独载体（n = 9）在家兔L5-L 6进行横突间腰椎融合。在术后2、4和6周时收集椎骨，并使用X线摄影、组织学和ISH评估融合块。在OP-1组中，术后6周，连续融合块桥接了L5和L 6横突。在2周时，II型和X型胶原在横突附近和横突间区域的中央部分均表达，对应于丰富的多灶性软骨。4周后，软骨内骨化从横突向中央部分进展。在6周时，II型和X型胶原蛋白的基因被限制在软骨内骨化的前端。单纯载体组未见融合瘤形成。结果表明，OP-1在PLF的早期阶段强烈刺激细胞并诱导软骨形成。然而，在晚期阶段，软骨内骨形成向中央部分发展成为主要过程，如在PLF与自体移植物中观察到的。因此，在OP-1诱导的PLF中，OP-1的成骨作用在早期阶段似乎相当强烈，但在晚期阶段则不然。
To elucidate the molecular mechanism by which osteogenic protein (OP)-1 induces posterolateral lumbar spine fusion (PLF), we analyzed the process of OP-1-induced PLF in an established rabbit model by means of in situ hybridization (ISH). Intertransverse process lumbar fusions were performed at L5-L6 in rabbits using OP-1 (n = 18) or carrier alone (n = 9). The vertebrae were harvested at 2, 4, and 6 weeks postsurgery, and fusion masses evaluated using radiography, histology and ISH. In the OP-1 group, a contiguous fusion mass bridged the L5 and L6 transverse processes by 6 weeks postsurgery. At 2 weeks, collagen types II and X were expressed both near the transverse process and at the central portion of the intertransverse process area, corresponding to abundant, multifocal cartilage. After 4 weeks, endochondral ossification progressed from the transverse process toward the central portion. At 6 weeks, genes for collagen types II and X were restricted at the front of endochondral ossification. In carrier-alone group, no fusion mass was formed. The results demonstrate that OP-1 vigorously stimulates cells and induces chondrogenesis in the early phase of PLF. In the late phase, however, endochondral bone formation progressing toward the central portion became the major process, as was observed in PLF with autograft. In OP-1-induced PLF, therefore, osteogenic action of OP-1 seems to be quite intensive in the early phase but not in the late phase.