Matrilin-3 as a putative effector of C-type natriuretic peptide signaling during TGF-β induced chondrogenic differentiation of mesenchymal stem cells

Abstract

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)-β induced in vitro chondrogenic differentiation of mesenchymal stem cells (MSCs). Previously characterized human trabecular bone derived MSCs were induced either with only TGF-β1 or with a combination of TGF-β1 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-β1 and CNP fed group in comparison to only TGF-β1 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.

TGF-β1 and GDF5 Act Synergistically to Drive the Differentiation of Human Adipose Stromal Cells toward Nucleus Pulposus-like Cells

“…We observed that the culture of hASCs in the presence of BM did not induce the expression of ACAN, COL2A1, CD24, OVOS2, and PAX1, while the expression of ACAN and COL2A1 was significantly increased in the CHM condition. A significant increase in CD24 expression was also noted in the CHM condition, as recently reported [36]. Confirming the results obtained with the first patients, hASCs cultivated in the NPM condition expressed significantly higher levels of ACAN, COL2A1, CD24, OVOS2, and PAX1 transcripts even though inter-individual variability was found (Fig.…”

A genome wide analysis of alternative splicing events during the osteogenic differentiation of human cartilage endplate-derived stem cells

“…In particular, it is a very powerful approach to analyze gene transcription and translation on a genome-wide scale to fully elucidate the mechanisms of osteogenic differentiation of stem cells. This approach has been applied to several previous studies to investigate the global gene expression, and post-transcriptional and epigenetic changes in the differentiation process (40)(41)(42)(43). However, little contribution has been made to obtain a comprehensive and coherent view of AS mechanisms of stem cell osteogenic differentiation in a genome-wide scale.…”

A genome-wide analysis of the gene expression profiles and alternative splicing events during the hypoxia-regulated osteogenic differentiation of human cartilage endplate-derived stem cells

“…At present, genome-wide transcription analysis is the predominant method used to study the mechanism of stem cell differentiation. Previous studies have used this tool to obtain a coherent view of the transcriptional and post-transcriptional alterations during the differentiation process ( 43 – 46 ). However, to the best of our knowledge, no previous studies have investigated the AS mechanisms of stem cell differentiation under hypoxic conditions on a genome-wide scale.…”