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Nfib Promotes Chondrocyte Proliferation and Inhibits Differentiation by Mildly Regulating Sox9 and Its Downstream Genes

Overview
Journal Mol Biol Rep
Specialty Molecular Biology
Date 2021 Oct 15
PMID 34651294
Citations 3
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Abstract

Background: Chondrocyte proliferation and differentiation play pivotal roles in regulating cartilage formation, endochondral bone formation, and repair. Cartilage damage and underdevelopment may cause severe joint diseases. Various transcription factors regulate cartilage development. Nuclear factor 1 B (Nfib) is a transcription factor that plays a regulatory role in various organs. However, the effect and mechanism of Nfib on the proliferation and differentiation of chondrocytes in cartilage are still largely unknown.

Methods And Results: In the present study, we investigated the gene expression patterns in primary chondrocytes with Nfib overexpression or silencing by RNA sequencing (RNA-seq) technology. The results showed that Nfib overexpression significantly up-regulated genes that are related to chondrocyte proliferation and extracellular matrix (ECM) synthesis and significantly down-regulated genes related to chondrocyte differentiation and ECM degradation. However, with Nfib silencing, the genes involved in promoting chondrocyte differentiation were significantly up-regulated, whereas those involved in promoting chondrocyte proliferation were significantly down-regulated. Furthermore, quantitative real-time PCR (qRT-PCR), western blot, alcian blue staining and immunofluorescence staining assays further confirmed that Nfib potentially promotes chondrocyte proliferation and extracellular synthesis but inhibits differentiation.

Conclusions: The molecular mechanism of Nfib in promoting chondrocyte proliferation and inhibiting differentiation was probably achieved by stimulating Sox9 and its downstream genes. Thus, this study adds new insights regarding the underlying molecular mechanism of transcriptional regulation in cartilage.

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References
1.
Oh C, Lu Y, Liang S, Mori-Akiyama Y, Chen D, de Crombrugghe B . SOX9 regulates multiple genes in chondrocytes, including genes encoding ECM proteins, ECM modification enzymes, receptors, and transporters. PLoS One. 2014; 9(9):e107577. PMC: 4168005. DOI: 10.1371/journal.pone.0107577. View

2.
Akiyama H, Chaboissier M, Martin J, Schedl A, de Crombrugghe B . The transcription factor Sox9 has essential roles in successive steps of the chondrocyte differentiation pathway and is required for expression of Sox5 and Sox6. Genes Dev. 2002; 16(21):2813-28. PMC: 187468. DOI: 10.1101/gad.1017802. View

3.
Wuelling M, Vortkamp A . Chondrocyte proliferation and differentiation. Endocr Dev. 2011; 21:1-11. DOI: 10.1159/000328081. View

4.
Kim I, Otto F, Zabel B, Mundlos S . Regulation of chondrocyte differentiation by Cbfa1. Mech Dev. 1999; 80(2):159-70. DOI: 10.1016/s0925-4773(98)00210-x. View

5.
Inada M, Yasui T, Nomura S, Miyake S, Deguchi K, Himeno M . Maturational disturbance of chondrocytes in Cbfa1-deficient mice. Dev Dyn. 1999; 214(4):279-90. DOI: 10.1002/(SICI)1097-0177(199904)214:4<279::AID-AJA1>3.0.CO;2-W. View