Fibroblast growth factor control of cartilage homeostasis.
Fibroblast growth factor control of cartilage homeostasis.
复制标题
DOI：
10.1002/jcb.24418
复制
发表时间：
2013-04
影响因子：
4
通讯作者：
Im, H. J.
中科院分区：
文献类型：
--
作者：
Ellman, M. B.;Yan, D.;Ahmadinia, K.;Chen, D.;An, H. S.;Im, H. J.
骨关节炎（OA）和退行性椎间盘疾病（DDD）是类似的疾病，涉及软骨组织的破坏，更好地了解涉及软骨退行性变的潜在生化过程可能允许开发旨在减缓疾病过程的新型生物疗法。成纤维细胞生长因子（FGF）家族的三个成员，FGF-2、FGF-18和FGF-8，被认为是软骨稳态的促进因素。FGF-2在关节和椎间盘（IVD）软骨中的作用存在争议，因为它与物种和年龄依赖性合成代谢或分解代谢事件有关。最近的证据表明，FGF-2选择性地激活FGF受体1 (FGFR1)，通过上调基质降解酶的产生，抑制细胞外基质（ECM）的积累和蛋白多糖的合成，以及关节炎状态特征细胞的聚集，在人关节软骨细胞和IVD组织中发挥分解代谢作用。另一方面，FGF-18很可能通过激活FGFR3通路，诱导ECM形成和软骨细胞分化，抑制细胞增殖，在人关节软骨细胞中发挥合成代谢作用。这些变化导致分散的软骨细胞或椎间盘细胞被丰富的基质包围。FGF-8的作用最近被确定为大鼠和家兔关节软骨的分解代谢介质，但其对成人关节软骨或IVD组织的确切生物学影响尚不清楚。现有证据表明，FGF-2/FGFR1拮抗剂、FGF-18/FGFR3激动剂和FGF-8拮抗剂（即抗FGF-8抗体）有望成为未来预防软骨退变和/或促进软骨再生和修复的潜在疗法。
Osteoarthritis (OA) and degenerative disc disease (DDD) are similar diseases involving the breakdown of cartilage tissue, and a better understanding of the underlying biochemical processes involved in cartilage degeneration may allow for the development of novel biologic therapies aimed at slowing the disease process. Three members of the fibroblast growth factor (FGF) family, FGF-2, FGF-18, and FGF-8, have been implicated as contributing factors in cartilage homeostasis. The role of FGF-2 is controversial in both articular and intervertebral disc (IVD) cartilage as it has been associated with species- and age-dependent anabolic or catabolic events. Recent evidence suggests that FGF-2 selectively activates FGF receptor 1 (FGFR1) to exert catabolic effects in human articular chondrocytes and IVD tissue via upregulation of matrix-degrading enzyme production, inhibition of extracellular matrix (ECM) accumulation and proteoglycan synthesis, and clustering of cells characteristic of arthritic states. FGF-18, on the other hand, most likely exerts anabolic effects in human articular chondrocytes by activating the FGFR3 pathway, inducing ECM formation and chondrogenic cell differentiation, and inhibiting cell proliferation. These changes result in dispersed chondrocytes or disc cells surrounded by abundant matrix. The role of FGF-8 has recently been identified as a catabolic mediator in rat and rabbit articular cartilage, but its precise biological impact on human adult articular cartilage or IVD tissue remains unknown. The available evidence reveals the promise of FGF-2/FGFR1 antagonists, FGF-18/FGFR3 agonists, and FGF-8 antagonists (i.e., anti-FGF-8 antibody) as potential therapies to prevent cartilage degeneration and/or promote cartilage regeneration and repair in the future.
登录
查看更多内容
影响因子：
2.3
作者：
Madry, Henning;Orth, Patrick;Cucchiarini, Magali
通讯作者：
Cucchiarini, Magali
影响因子：
7
作者：
Chuma, H;Mizuta, H;Hiraki, Y
通讯作者：
Hiraki, Y
影响因子：
--
作者：
Li, Xin;Ellman, Michael;Muddasani, Prasuna;Wang, James H. -C.;Cs-Szabo, Gabriella;van Wijnen, Andre J.;Im, Hee-Jeong
通讯作者：
Im, Hee-Jeong
DOI：
10.1038/nrd2792
发表时间：
2009-03
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
通讯作者：
--
影响因子：
7
作者：
Ellsworth, JL;Berry, J;Hughes, SD
通讯作者：
Hughes, SD