FOXC1和FOXC2在骨生成中的作用及其在骨再生和重塑中的治疗潜力

IF 3.5 3区 生物学 Q3 CELL BIOLOGY
Ali Molaei , Emad Molaei , A. Wallace Hayes , Gholamreza Karimi
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引用次数: 0

摘要

骨是一种非凡的动态组织,不断经历复杂的发育、修复和终身重塑过程,对维持骨骼完整性、促进损伤恢复和保持整体健康至关重要。间充质干细胞(MSCs)是这些过程的核心,其特点是具有自我更新能力,多能分化(包括成骨细胞),并在分泌生长因子和重塑细胞外基质方面发挥关键作用。高度保守的转录因子FOXC1和FOXC2对正确的骨骼发育至关重要,深刻影响膜内和软骨内成骨。除了这些已确立的发育功能外,最近的证据阐明了它们在积极调节间充质干细胞成骨承诺和促进成骨细胞分化方面的关键新兴作用,特别是在细胞早期阶段。例如,FOXC1协调关键的成骨和软骨转录因子的表达,如SOX9(对软骨内成骨至关重要)和MSX2(在膜内骨形成中至关重要)。反过来,FOXC2通过激活WNT/β-catenin信号通路显著促进成骨细胞成熟。此外,令人信服的实验研究现在直接涉及FOXC1和FOXC2在成人骨修复,骨矿物质密度(BMD)的维持和关节健康的调节。这将它们的发育意义与成人骨骼疾病的实质性治疗潜力联系起来。这篇综述综合了目前对FOXC1和FOXC2在骨生物学中的发育和新兴成人角色的理解,并重点探讨了它们在成骨中的潜在分子和细胞机制。我们还批判性地讨论了它们在常见骨骼疾病(如骨折、骨质疏松症和骨关节炎)中的治疗潜力,说明了胚胎骨形成的见解如何直接为增强成人骨再生和重塑提供新的策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
FOXC1 and FOXC2 in Osteogenesis: Emerging roles and therapeutic potential in bone regeneration and remodeling
Bone is a remarkable dynamic tissue, continually undergoing intricate processes of development, repair, and lifelong remodeling, all vital for maintaining skeletal integrity, facilitating injury recovery, and preserving overall health. Mesenchymal stem cells (MSCs) are central to these processes, characterized by their self-renewal capacity, multipotent differentiation (including osteoblasts), and crucial roles in secreting growth factors and remodeling the extracellular matrix.
The highly conserved transcription factors FOXC1 and FOXC2 are crucial for correct skeletal development, profoundly influencing both intramembranous and endochondral ossification. Beyond these established developmental functions, recent evidence illuminates their critical emerging roles in actively regulating MSC osteogenic commitment and promoting osteoblastic differentiation, particularly in early cellular stages. FOXC1, for instance, orchestrates the expression of key osteogenic and chondrogenic transcription factors such as SOX9 (vital for endochondral ossification) and MSX2 (paramount in intramembranous bone formation). FOXC2, in turn, significantly contributes to osteoblast maturation through robust activation of the WNT/β-catenin signaling pathway. Furthermore, compelling experimental studies now directly implicate FOXC1 and FOXC2 in adult bone repair, the maintenance of bone mineral density (BMD), and the modulation of joint health. This bridges their developmental significance to substantial therapeutic potential in adult skeletal pathologies.
This review comprehensively synthesizes current understanding of the developmental and emerging adult roles of FOXC1 and FOXC2 in bone biology, with a focused exploration of their underlying molecular and cellular mechanisms in osteogenesis. We also critically discuss their promising therapeutic potential in prevalent skeletal conditions such as fractures, osteoporosis, and osteoarthritis, illustrating how insights from embryonic bone formation can directly inform novel strategies for enhancing adult bone regeneration and remodeling.
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来源期刊
Experimental cell research
Experimental cell research 医学-细胞生物学
CiteScore
7.20
自引率
0.00%
发文量
295
审稿时长
30 days
期刊介绍: Our scope includes but is not limited to areas such as: Chromosome biology; Chromatin and epigenetics; DNA repair; Gene regulation; Nuclear import-export; RNA processing; Non-coding RNAs; Organelle biology; The cytoskeleton; Intracellular trafficking; Cell-cell and cell-matrix interactions; Cell motility and migration; Cell proliferation; Cellular differentiation; Signal transduction; Programmed cell death.
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