Bone morphogenetic protein-2-mediated pain and inflammation in a rat model of posterolateral arthrodesis.
Bone morphogenetic protein-2-mediated pain and inflammation in a rat model of posterolateral arthrodesis.
复制标题
DOI：
10.1186/s12868-016-0314-3
复制
发表时间：
2016-12-01
期刊：
影响因子：
2.4
通讯作者：
Symes AJ
中科院分区：
文献类型：
--
作者：
Mitchell K;Shah JP;Dalgard CL;Tsytsikova LV;Tipton AC;Dmitriev AE;Symes AJ
骨形态发生蛋白-2(BMP-2)是一种多效性、分泌性分子，具有多种作用。BMP-2刺激骨骼生长的强大能力促使其在关节融合术(脊柱融合)中得到广泛的临床应用。然而，使用BMP-2治疗的患者术后疼痛增加的报道越来越多。确定BMP-2是否直接导致疼痛，或者是否导致神经炎症，从而降低疼痛的阈值，对于开发治疗干预措施非常重要。因此，我们模拟了BMP-2用于腰椎后路融合的临床应用，方法是将可吸收的胶原海绵与重组人BMP-2(rhBMP-2)或载体植入大鼠脊柱L4-L5横突上方。通过基因芯片分析，我们发现植入rhBMP-2的可吸收胶原海绵导致邻近背根神经节(DRG)许多致炎基因表达的改变，这表明植入rhBMP-2/可吸收胶原海绵在DRG-2中触发了强烈的神经炎性反应。有趣的是，直接对DRG外植体进行BMP-2处理导致了非特异性促炎基因表达的变化。在可吸收胶原海绵中植入重组人骨形成蛋白-2的大鼠也表现出短暂的热和机械敏感性变化，这表明将重组人骨形态发生蛋白-2应用于腰椎可以增加疼痛敏感性。免疫组织化学分析显示，植入rhBMP-2/可吸收胶原海绵或单独植入可吸收胶原海绵的大鼠背根神经节和脊神经中有巨噬细胞浸润，但在手术后未植入可吸收胶原海绵的大鼠中未见巨噬细胞浸润，提示海绵参与了生物反应。事实上，对植入了不含重组人骨形态发生蛋白-2的可吸收胶原海绵的大鼠背根节的分析显示，与仅接受手术的大鼠的背根节不同，基因表达发生了显著变化。我们的数据表明，在腰椎植入重组人骨形成蛋白-2/可吸收胶原海绵可在背根节引发强烈的神经炎性反应。然而，重要的是，这些BMP-2效应可能部分是通过对可吸收的胶原海绵的反应来调节的。
Bone morphogenetic protein-2 (BMP-2) is a pleiotropic, secreted molecule with diverse effects. The potent ability of BMP-2 to stimulate bone growth prompted its widespread clinical use for arthrodesis (spine fusion). However, elevated post-operative pain in patients treated with BMP-2 has been increasingly reported. Determining whether BMP-2 induces pain directly or whether it induces neuroinflammation, which could lower the threshold for pain, is important for developing therapeutic interventions. We therefore modeled the clinical use of BMP-2 for posterior lumbar fusion by implanting absorbable collagen sponges soaked with either recombinant human BMP-2 (rhBMP-2) or vehicle above the L4–L5 transverse processes of rat spine. Using microarray analysis we found that implantation of rhBMP-2-soaked absorbable collagen sponges resulted in altered expression of numerous pro-inflammatory genes in the adjacent dorsal root ganglia (DRG) showing that implantation of rhBMP-2/absorbable collagen sponges triggers potent neuroinflammatory responses in the DRG-2. Interestingly, direct BMP-2 treatment of DRG explants resulted in changes in gene expression that were not specifically pro-inflammatory. Rats implanted with rhBMP-2 in absorbable collagen sponges also exhibited a transient change in thermal and mechanical sensitivity indicating that rhBMP-2 applied to the lumbar spine could increase pain sensitivity. Immunohistochemical analysis indicated macrophage infiltration in the DRG and spinal nerve in rats implanted with rhBMP-2/absorbable collagen sponges or absorbable collagen sponges alone, but not in rats that underwent surgery without implantation of the absorbable collagen sponges suggesting that the sponges contributed to the biological response. Indeed, analysis of DRGs taken from rats implanted with absorbable collagen sponges without rhBMP-2 showed a significant change in gene expression distinct from DRGs from rats undergoing surgery only. Our data indicate that implantation of rhBMP-2/absorbable collagen sponges on the lumbar spine triggers potent neuroinflammatory responses in the DRG. Importantly, however, these BMP-2 effects may be partially mediated through a response to the absorbable collagen sponges.
登录
查看更多内容
影响因子：
3
作者：
Lee, Kwang-Bok;Taghavi, Cyrus E.;Wang, Jeffrey C.
通讯作者：
Wang, Jeffrey C.
影响因子：
2.7
作者：
McLachlan, Elspeth M.;Hu, Ping
通讯作者：
Hu, Ping
影响因子：
5.3
作者：
Dmitriev, Anton E.;Castner, Suzanne;Symes, Aviva J.
通讯作者：
Symes, Aviva J.
影响因子：
4.7
作者：
Susarla BT;Laing ED;Yu P;Katagiri Y;Geller HM;Symes AJ
通讯作者：
Symes AJ
影响因子：
7.4
作者：
Mitchell, Kendall;Yang, Hsiu-Ying T.;Iadarola, Michael J.
通讯作者：
Iadarola, Michael J.