Abstract:
Fibroblast growth factor 8 (FGF-8), also known as androgen-induced growth factor (AIGF), is presumed to be a potent mitogenic cytokine that plays important roles in early embryonic development, brain formation and limb development. In the bone environment, FGF-8 produced or received by chondrocyte precursor cells binds to fibroblast growth factor receptor (FGFR), causing different levels of activation of downstream signalling pathways, such as phospholipase C gamma (PLCγ)/Ca2+ , RAS/mitogen-activated protein kinase-extracellular regulated protein kinases (RAS/MAPK-MEK-ERK), and Wnt-β-catenin-Axin2 signalling, and ultimately controlling chondrocyte proliferation, differentiation, cell survival and migration. However, the molecular mechanism of FGF-8 in normal or pathological cartilage remains unclear, and thus, FGF-8 represents a novel exploratory target for studies of chondrocyte development and cartilage disease progression. In this review, studies assessing the relationship between FGF-8 and chondrocytes that have been published in the past 5 years are systematically summarized to determine the probable mechanism and physiological effect of FGF-8 on chondrocytes. Based on the existing research results, a therapeutic regimen targeting FGF-8 is proposed to explore the possibility of treating chondrocyte-related diseases.
摘要:
成纤维细胞生长因子8(FGF-8),也称为雄激素诱导生长因子(AIGF),被认为是一种有效的促有丝分裂细胞因子,在早期胚胎发育中起着重要作用,大脑形成和肢体发育。在骨骼环境中,软骨细胞前体细胞产生或接受的FGF-8与成纤维细胞生长因子受体(FGFR)结合,导致不同水平的下游信号通路的激活,如磷脂酶Cγ(PLCγ)/Ca2+,RAS/丝裂原活化蛋白激酶-细胞外调节蛋白激酶(RAS/MAPK-MEK-ERK),和Wnt-β-连环蛋白-Axin2信号,最终控制软骨细胞的增殖,分化,细胞存活和迁移。然而,FGF-8在正常或病理性软骨中的分子机制尚不清楚,因此,FGF-8代表了软骨细胞发育和软骨疾病进展研究的新的探索性靶标。在这次审查中,系统总结了过去5年中发表的评估FGF-8与软骨细胞之间关系的研究,以确定FGF-8对软骨细胞的可能机制和生理作用。在现有研究成果的基础上,提出了一种靶向FGF-8的治疗方案,以探索治疗软骨细胞相关疾病的可能性。