Functional analyses reveal the essential role of SOX6 and RUNX2 in the communication of chondrocyte and osteoblast

Zhang, Y.; Yang, Tie‐Lin; Li, X.; Guo, Yan

doi:10.1007/s00198-014-2882-3

Cited by 17 publications

(12 citation statements)

References 24 publications

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“…GDF5 , also called bone morphogenetic protein (BMP)-14 and cartilage-derived morphogenetic protein (CDMP)-1, is a member of the transforming growth factor β (TGF-β) superfamily and plays critical roles in organ development processes including bone, cartilage, ligament, and joint formation [45]. SOX6 , a member of the D subfamily of sex determining region y-box (SRY-box)-related transcription factors, is a crucial transcription factor that regulates chondrogenesis and endochondral ossification [46]. A previous study showed that rhGDF-5 induces the osteogenic differentiation of LF cells through the activation of ERK1/2 and p38 mitogen-activated protein kinase (MAPK) [40].…”

Section: Discussionmentioning

confidence: 99%

MiR-132-3p Regulates the Osteogenic Differentiation of Thoracic Ligamentum Flavum Cells by Inhibiting Multiple Osteogenesis-Related Genes

Chen

Fan

et al. 2016

IJMS

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Ossification of the ligamentum flavum (OLF) is a disorder of heterotopic ossification of spinal ligaments and is the main cause of thoracic spinal canal stenosis. Previous studies suggested that miR-132-3p negatively regulates osteoblast differentiation. However, whether miR-132-3p is involved in the process of OLF has not been investigated. In this study, we investigated the effect of miR-132-3p and its target genes forkhead box O1 (FOXO1), growth differentiation factor 5 (GDF5) and SRY-box 6 (SOX6) on the osteogenic differentiation of ligamentum flavum (LF) cells. We demonstrated that miR-132-3p was down-regulated during the osteogenic differentiation of LF cells and negatively regulated the osteoblast differentiation. Further, miR-132-3p targeted FOXO1, GDF5 and SOX6 and down-regulated the protein expression of these genes. Meanwhile, FOXO1, GDF5 and SOX6 were up-regulated after osteogenic differentiation and the down-regulation of endogenous FOXO1, GDF5 or SOX6 suppressed the osteogenic differentiation of LF cells. In addition, we also found FOXO1, GDF5 and SOX6 expression in the ossification front of OLF samples. Overall, these results suggest that miR-132-3p inhibits the osteogenic differentiation of LF cells by targeting FOXO1, GDF5 and SOX6.

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Section: Discussionmentioning

confidence: 99%

MiR-132-3p Regulates the Osteogenic Differentiation of Thoracic Ligamentum Flavum Cells by Inhibiting Multiple Osteogenesis-Related Genes

Chen

Fan

et al. 2016

IJMS

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“…25 The CpG correlating to the highest number of transcripts (5% FDR) lies within an enhancer in the 3 0 end of SOX6, which is well known to have a significant function in cartilage and bone. 26 Ubiquitin Specific Peptidase 2 (USP2) (6 th and 7 th from top) is induced by the osteotropic agents PTH, PTHrP, and PGE2, 27 but its specific function in bone is not yet known.…”

Section: Methylation At Selected Cpgs Correlates Significantly To a Hmentioning

confidence: 99%

Distinct DNA methylation profiles in bone and blood of osteoporotic and healthy postmenopausal women

et al. 2017

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DNA methylation affects expression of associated genes and may contribute to the missing genetic effects from genome-wide association studies of osteoporosis. To improve insight into the mechanisms of postmenopausal osteoporosis, we combined transcript profiling with DNA methylation analyses in bone. RNA and DNA were isolated from 84 bone biopsies of postmenopausal donors varying markedly in bone mineral density (BMD). In all, 2529 CpGs in the top 100 genes most significantly associated with BMD were analyzed. The methylation levels at 63 CpGs differed significantly between healthy and osteoporotic women at 10% false discovery rate (FDR). Five of these CpGs at 5% FDR could explain 14% of BMD variation. To test whether blood DNA methylation reflect the situation in bone (as shown for other tissues), an independent cohort was selected and BMD association was demonstrated in blood for 13 of the 63 CpGs. Four transcripts representing inhibitors of bone metabolism-MEPE, SOST, WIF1, and DKK1-showed correlation to a high number of methylated CpGs, at 5% FDR. Our results link DNA methylation to the genetic influence modifying the skeleton, and the data suggest a complex interaction between CpG methylation and gene regulation. This is the first study in the hitherto largest number of postmenopausal women to demonstrate a strong association among bone CpG methylation, transcript levels, and BMD/fracture. This new insight may have implications for evaluation of osteoporosis stage and susceptibility.

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“…SOX6 is a member of the SOX family of transcription factors that is expressed in the cartilage and has an essential role in chondrocyte differentiation, cartilage formation and endochondral bone formation 38 . In fact, a recent functional study revealed that SOX6 is involved in the coordination of chondrogenesis and osteogenesis 39 . The relationship between rs7117858 SNP in SOX6 and certain osteoporosis phenotypes has been previously investigated in mixed populations [23][24][25][26]32 .…”

Section: Resultsmentioning

confidence: 99%

SOX6 rs7117858 polymorphism is associated with osteoporosis and obesity‐related phenotypes

Correa‐Rodríguez

Schmidt-RíoValle

Rueda‐Medina

2018

Eur J Clin Investigation

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Functional analyses reveal the essential role of SOX6 and RUNX2 in the communication of chondrocyte and osteoblast

Abstract: Our study first reveals that SOX6 and RUNX2 play important roles in the chondrogenesis-osteogenesis coordination. This finding enriches the limited understanding about this coordination and unravels the novel function of SOX6 and RUNX2 in the endochondral ossification.

Cited by 17 publications

References 24 publications

MiR-132-3p Regulates the Osteogenic Differentiation of Thoracic Ligamentum Flavum Cells by Inhibiting Multiple Osteogenesis-Related Genes

MiR-132-3p Regulates the Osteogenic Differentiation of Thoracic Ligamentum Flavum Cells by Inhibiting Multiple Osteogenesis-Related Genes

Distinct DNA methylation profiles in bone and blood of osteoporotic and healthy postmenopausal women

SOX6 rs7117858 polymorphism is associated with osteoporosis and obesity‐related phenotypes

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