Matrilin-3 as a putative effector of C-type natriuretic peptide signaling during TGF-β induced chondrogenic differentiation of mesenchymal stem cells
Matrilin-3 as a putative effector of C-type natriuretic peptide signaling during TGF-β induced chondrogenic differentiation of mesenchymal stem cells
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DOI：
10.1007/s11033-014-3448-3
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发表时间：
2014-09-01
影响因子：
2.8
通讯作者：
Tufan, A. Cevik
中科院分区：
文献类型：
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作者：
Babadagli, Mustafa Ege;Tezcan, Berna;Tufan, A. Cevik
C型利钠肽（CNP）信号转导被认为是软骨内骨发育过程中软骨形成分化的重要调节因子。该初步研究进一步研究了转化生长因子（TGF）-β诱导的间充质干细胞（MSC）体外软骨形成分化中CNP信号传导的推定效应子和/或靶标。先前表征的人小梁骨来源的MSC在微团培养物中仅用TGF-β 1或用TGF-β 1和CNP的组合诱导10或20天。在培养的第10天或第20天分析这两组之间的全基因组基因表达谱变化。结果显示，只有7个基因的表达变化在TGF-β 1和CNP饲喂组中是仅TGF-β 1饲喂组的4倍或更高。上调表达的基因包括matrilin-3（MATN 3）、吞噬和细胞运动1（ELMO 1）、CD 24和DCN 1、cullin neddylation 1缺陷型结构域1（DCUN 1D 1）。另一方面，下调的基因包括LIM结构域激酶2（LIMK 2）、尤文肉瘤断点区1和鸟嘌呤核苷酸结合蛋白（G蛋白）γ 12（GNG 12）。RT-PCR结果证实MATN 3基因表达上调。关于CNP信号传导和MATN 3在软骨形成中的功能的已知文献彼此匹配，并表明MATN 3在该过程中是CNP信号传导的推定效应物和/或靶标。
C-type natriuretic peptide (CNP) signaling has been implicated as an important regulator of chondrogenic differentiation during endochondral bone development. This preliminary study further investigated the putative effectors and/or targets of CNP signaling in transforming growth factor (TGF)-beta induced in vitro chondrogenic differentiation of mesenchymal stem cells (MSCs). Previously characterized human trabecular bone derived MSCs were induced either with only TGF-beta 1 or with a combination of TGF-beta 1 and CNP in micromass culture for 10 or 20 days. Genome wide gene expression profile changes in between these two groups were analyzed on day-10 or day-20 of culture. Results revealed that there were only 7 genes, whose expression change was fourfolds or higher in TGF-beta 1 and CNP fed group in comparison to only TGF-beta 1 fed group. The up-regulated genes included matrilin-3 (MATN3), engulfment and cell motility 1 (ELMO1), CD24, and DCN1, defective in cullin neddylation 1, domain containing 1 (DCUN1D1). The down-regulated genes, on the other hand, included LIM domain kinase 2 (LIMK2), Ewing sarcoma breakpoint region 1, and guanine nucleotide binding protein (G protein), gamma 12 (GNG12). The up-regulation of MATN3 was confirmed on the basis of RT-PCR. The known literature on both CNP signaling and MATN3 function in chondrogenesis match with each other and suggest MATN3 as a putative effector and/or target of CNP signaling during this process.