Expression of receptors for putative anabolic growth factors in human intervertebral disc: implications for repair and regeneration of the disc
Expression of receptors for putative anabolic growth factors in human intervertebral disc: implications for repair and regeneration of the disc
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DOI：
10.1002/path.1862
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发表时间：
2005-12-01
影响因子：
7.3
通讯作者：
Hoyland, JA
中科院分区：
文献类型：
--
作者：
Le Maitre, CL;Richardson, SMA;Hoyland, JA
腰痛 (LBP) 是一种常见的、使人衰弱且具有重要经济意义的疾病。目前的证据表明“退变”导致的椎间盘（IVD）基质损失是腰痛的主要原因。 IVD 的退化涉及降解酶的增加和细胞外基质 (ECM) 成分的减少，该过程由一系列细胞因子和生长因子控制。研究表明，使用合成代谢生长因子来再生 IVD 的正常基质，从而恢复椎间盘高度并逆转退行性椎间盘疾病。然而，要使此类疗法取得成功，靶细胞（即椎间盘细胞）表达适当的受体至关重要。这项免疫组织化学研究首次研究了四种潜在有益的生长因子受体（即 TGF beta RII、BMPRII、FGFR3 和 IGFRI）在非简并和简并人类 IVD 中的表达和定位。对正常和退变椎间盘区域的受体表达进行定量，结果表明，髓核（NP）和内纤维环（IAF）细胞表达的四种生长因子受体的水平显着较高。在非变性和变性活检中四种生长因子的表达没有显着差异。然而，在内生血管中观察到 TGF beta RII、FGFR3 和 IGFRI 的表达，但未观察到 BMP RII 的表达，这是该疾病病因学的部分特征。总之，本研究证明，在非退化和退化椎间盘中，四种生长因子受体在 NP 和 IAF 的软骨细胞样细胞中以相似的水平表达，暗示在正常椎间盘稳态中的作用，并表明将这些生长因子应用于退化的人类 IVD 将刺激基质产生。然而，一些生长因子受体在向内生长的血管上的表达可能在治疗方法中存在问题。版权所有 (c) 2005 大不列颠及爱尔兰病理学会。约翰·威利圣子有限公司出版
Low back pain (LBP) is a common, debilitating and economically important disorder. Current evidence implicates loss of intervertebral disc (IVD) matrix consequent upon 'degeneration' as a major cause of LBP. Degeneration of the IVD involves increases in degradative enzymes and decreases in the extracellular matrix (ECM) component in a process that is controlled by a range of cytokines and growth factors. Studies have suggested using anabolic growth factors to regenerate the normal matrix of the IVD, hence restoring disc height and reversing degenerative disc disease. However, for such therapies to be successful it is vital that the target cells (i.e. the disc cells) express the appropriate receptors. This immunohistochemical study has for the first time investigated the expression and localization of four potentially beneficial growth factor receptors (i.e. TGF beta RII, BMPRII, FGFR3 and IGFRI) in non-degenerate and degenerate human IVDs. Receptor expression was quantified across regions of the normal and degenerate disc and showed that cells of the nucleus pulposus (NP) and inner annulus fibrosus (IAF) expressed significantly higher levels of the four growth factor receptors investigated. There were no significant differences between the four growth factor expression in non-degenerate and degenerate biopsies. However, expression of TGF beta RII, FGFR3 and IGFRI, but not BMP RII, were observed in the ingrowing blood vessels that characterize part of the disease aetiology. In conclusion, this study has demonstrated the expression of the four growth factor receptors at similar levels in the chondrocyte-like cells of the NP and IAF in both non-degenerate and degenerate discs, implicating a role in normal disc homeostasis and suggesting that the application of these growth factors to the degenerate human IVD would stimulate matrix production. However, the expression of some of the growth factor receptors on ingrowing blood vessels might be problematic in a therapeutic approach. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley St Sons, Ltd.