The Influence of TGF-β3, EGF, and BGN on SOX9 and RUNX2 Expression in Human Chondrogenic Progenitor Cells

The Influence of TGF-β3, EGF, and BGN on SOX9 and RUNX2 Expression in Human Chondrogenic Progenitor Cells
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DOI:
10.1369/0022155418811645
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发表时间:
2019-02-01
影响因子:
3.2
通讯作者:
Miosge, Nicolai
Miosge, Nicolai
中科院分区:
生物学3区
文献类型:
--
作者:
Janssen, Jerome Nicolas;Batschkus, Sarah;Miosge, Nicolai

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骨关节炎(OA)是最常见的慢性关节疾病,合成代谢和分解代谢过程之间的不平衡导致细胞外基质降解。 TGF-β 3(转化生长因子β-3)和表皮生长因子(EGF)影响软骨细胞的骨软骨形成潜力。在这项研究中,我们比较了健康和患病软骨细胞中 TGF-β 3 和 EGF 途径以及双糖链蛋白聚糖 (BGN) 中介质和受体的表达。此外,我们使用软骨形成祖细胞 (CPC) 进行体外刺激和敲低实验,以阐明 TGF-β 3 和 EGF 对软骨形成潜力的影响。我们的结果表明,患病软骨细胞和 CPC 中 TGF-β 受体 1 型 (TGFBRI) 和表皮生长因子受体 (EGFR) 的表达发生了改变。此外,TGF-β 3 和 EGF 刺激影响 CPC 中 BGN、SRY(性别决定区 Y)-box 9 (SOX9) 和 Runt 相关转录因子 2 (RUNX2) 的表达水平。因此,TGFBRI 和 EGFR 表达的变化可能导致 OA 晚期出现退行性和再生效应。
Osteoarthritis (OA) is the most common chronic joint disease and leads to the degradation of the extracellular matrix by an imbalance between anabolic and catabolic processes. TGF-beta 3 (transforming growth factor beta-3) and epidermal growth factor (EGF) influence the osteochondrogenic potential of chondrocytes. In this study, we compared the expression of mediators and receptors in the TGF-beta 3 and EGF pathways, as well as biglycan (BGN), in healthy and diseased chondrocytes. Furthermore, we used chondrogenic progenitor cells (CPCs) for in vitro stimulation and knockdown experiments to elucidate the effects of TGF-beta 3 and EGF on the chondrogenic potential. Our results demonstrate that the expression of TGF-beta receptor type-1 (TGFBRI) and epidermal growth factor receptor (EGFR) is altered in diseased chondrocytes as well as in CPCs. Moreover, TGF-beta 3 and EGF stimulation influenced the expression levels of BGN, SRY (sex determining region Y)-box 9 (SOX9), and Runt-related transcription factor 2 (RUNX2) in CPCs. Therefore, changes in TGFBRI and EGFR expression likely contribute to the degenerative and regenerative effects seen in late stages of OA.