Biological impact of the fibroblast growth factor family on articular cartilage and intervertebral disc homeostasis
Biological impact of the fibroblast growth factor family on articular cartilage and intervertebral disc homeostasis
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DOI：
10.1016/j.gene.2008.04.019
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发表时间：
2008-08-15
期刊：
影响因子：
3.5
通讯作者：
Im, Hee-Jeong
中科院分区：
文献类型：
--
作者：
Ellman, Michael B.;An, Howard S.;Im, Hee-Jeong
成纤维细胞生长因子（FGF）家族的两个成员，碱性FGF（bFGF）和FGF-18，已经涉及关节和椎间盘（IVD）软骨稳态的调节。关于bFGF在软骨基质合成和降解中的确切作用，来自各种物种的bFGF研究产生了相互矛盾的结果。相比之下，FGF-18是一种众所周知的参与软骨形成和关节软骨修复的合成代谢生长因子。在这篇综述中，我们研究了bFGF和FGF-18在关节和IVD软骨中的生物学作用，每个因子结合的特定细胞表面受体，以及用于发挥其生物学作用的独特信号级联和分子途径。有证据表明，bFGF选择性激活FGF受体1（FGFR 1），通过上调基质降解酶活性、抑制基质产生和增加细胞增殖，在人关节软骨细胞和IVD组织中发挥降解作用，导致关节炎状态中观察到的细胞聚集。另一方面，FGF-18最有可能通过激活FGFR 3、增加基质形成和细胞分化同时抑制细胞增殖、导致分散的细胞被丰富的基质包围而在人关节软骨细胞中发挥合成代谢作用。来自体外和体内研究的结果表明bFGF和FGFR 1拮抗剂以及FGF-18和FGFR 3激动剂作为潜在疗法在未来预防软骨变性和/或促进软骨再生和修复的潜在有用性。(C)2008 Elsevier B. V.保留所有权利。
Two members of the fibroblast growth factor (FGF) family, basic FGF (bFGF) and FGF-18, have been implicated in the regulation of articular and intervertebral disc (IVD) cartilage homeostasis. Studies on bFGF from a variety of species have yielded contradictory results with regards to its precise role in cartilage matrix synthesis and degradation. In contrast, FGF-18 is a well-known anabolic growth factor involved in chondrogenesis and articular cartilage repair. In this review, we examined the biological actions of bFGF and FGF-18 in articular and IVD cartilage, the specific cell surface receptors bound by each factor, and the unique signaling cascades and molecular pathways utilized to exert their biological effects. Evidence suggests that bFGF selectively activates FGF receptor 1 (FGFR1) to exert degradative effects in both human articular chondrocytes and IVD tissue via upregulation of matrix-degrading enzyme activity, inhibition of matrix production, and increased cell proliferation resulting in clustering of cells seen in arthritic states. FGF-18, on the other hand, most likely exerts anabolic effects in human articular chondrocytes by activating FGFR3, increasing matrix formation and cell differentiation while inhibiting cell proliferation, leading to dispersed cells surrounded by abundant matrix. The results from in vitro and in vivo studies suggest the potential usefulness of bFGF and FGFR1 antagonists, as well as FGF-18 and FGFR3 agonists, as potential therapies to prevent cartilage degeneration and/or promote cartilage regeneration and repair in the future. (C) 2008 Elsevier B.V. All rights reserved.