The molecular mechanisms of glycosaminoglycan biosynthesis regulating chondrogenesis and endochondral ossification
The molecular mechanisms of glycosaminoglycan biosynthesis regulating chondrogenesis and endochondral ossification
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DOI：
10.1016/j.lfs.2023.122243
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发表时间：
2023-11-18
期刊：
影响因子：
6.1
通讯作者：
Zhang，Hui
中科院分区：
文献类型：
--
作者：
Chen，Yongjian;Mehmood，Khalid;Zhang，Hui
软骨细胞分化和软骨内成骨障碍是骨骼发育障碍的主要潜在因素，包括胫骨发育不良（TD）、骨关节炎（OA）、软骨发育不良（ACH）和多发性骨骺发育不良（MED）。了解这些疾病的细胞和分子发病机制对于解决由糖胺聚糖合成受损引起的骨科疾病至关重要。糖胺聚糖是一个广义的术语，指的是蛋白多糖大分子中的聚糖成分。它是软骨细胞外基质的重要组成部分，在基因转录、信号转导和软骨细胞分化等多种生物过程中起着至关重要的作用。近年来的研究表明，糖胺聚糖生物合成通过调节多种生长因子和信号分子，在软骨细胞分化和软骨内成骨过程中起调节作用。如糖胺聚糖参与介导Wnt、TGF-β、FGF、Ihh-PTHrP、O-GlcNAc糖基化等通路，与转录因子SOX9、bmp、TGF-β、Runx2相互作用，调节软骨细胞分化和软骨内成骨。为了提出解决由糖胺聚糖生物合成受损引起的骨科疾病的创新方法，我们对调节软骨细胞分化和软骨内成骨的软骨细胞糖胺聚糖生物合成的分子机制进行了全面的综述。我们的分析考虑了基因、糖蛋白和相关信号通路在软骨形成和软骨内成骨过程中的作用。
Disorders of chondrocyte differentiation and endochondral osteogenesis are major underlying factors in skeletal developmental disorders, including tibial dysplasia (TD), osteoarthritis (OA), chondrodysplasia (ACH), and multiple epiphyseal dysplasia (MED). Understanding the cellular and molecular pathogenesis of these disorders is crucial for addressing orthopedic diseases resulting from impaired glycosaminoglycan synthesis. Glycosaminoglycan is a broad term that refers to the glycan component of proteoglycan macromolecules. It is an essential component of the cartilage extracellular matrix and plays a vital role in various biological processes, including gene transcription, signal transduction, and chondrocyte differentiation. Recent studies have demonstrated that glycosaminoglycan biosynthesis plays a regulatory role in chondrocyte differentiation and endochondral osteogenesis by modulating various growth factors and signaling molecules. For instance, glycosaminoglycan is involved in mediating pathways such as Wnt, TGF-β, FGF, Ihh-PTHrP, and O-GlcNAc glycosylation, interacting with transcription factors SOX9, BMPs, TGF-β, and Runx2 to regulate chondrocyte differentiation and endochondral osteogenesis. To propose innovative approaches for addressing orthopedic diseases caused by impaired glycosaminoglycan biosynthesis, we conducted a comprehensive review of the molecular mechanisms underlying chondrocyte glycosaminoglycan biosynthesis, which regulates chondrocyte differentiation and endochondral osteogenesis. Our analysis considers the role of genes, glycoproteins, and associated signaling pathways during chondrogenesis and endochondral ossification.