The role for runt related transcription factor 2 (RUNX2) as a transcriptional repressor in luteinizing granulosa cells

Park, Eun Sil; Park, Jiyeon; Franceschi, Renny T.; Jo, Misung

doi:10.1016/j.mce.2012.06.005

Cited by 24 publications

(15 citation statements)

References 73 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…6C ). This expression pattern is concordant with Runx function in the female reproductive system of mammals [69] , [70] and Drosophila [71] and may therefore hint at a possible role of Runx in conserved pathways of ovarian function. In gnathostomes, Runx proteins are central regulators in the development of cellular cartilage and ossification of endochondral bone [28] , [72] .…”

Section: Resultssupporting

confidence: 62%

Characterization of the Runx Gene Family in a Jawless Vertebrate, the Japanese Lamprey (Lethenteron japonicum)

et al. 2014

View full text Add to dashboard Cite

The cyclostomes (jawless vertebrates), comprising lampreys and hagfishes, are the sister group of jawed vertebrates (gnathostomes) and are hence an important group for the study of vertebrate evolution. In mammals, three Runx genes, Runx1, Runx2 and Runx3, encode transcription factors that are essential for cell proliferation and differentiation in major developmental pathways such as haematopoiesis, skeletogenesis and neurogenesis and are frequently associated with diseases. We describe here the characterization of Runx gene family members from a cyclostome, the Japanese lamprey (Lethenteron japonicum). The Japanese lamprey contains three Runx genes, RunxA, RunxB, and RunxC. However, phylogenetic and synteny analyses suggest that they are not one-to-one orthologs of gnathostome Runx1, Runx2 and Runx3. The major protein domains and motifs found in gnathostome Runx proteins are highly conserved in the lamprey Runx proteins. Although all gnathostome Runx genes each contain two alternative promoters, P1 (distal) and P2 (proximal), only lamprey RunxB possesses the alternative promoters; lamprey RunxA and RunxC contain only P2 and P1 promoter, respectively. Furthermore, the three lamprey Runx genes give rise to fewer alternative isoforms than the three gnathostome Runx genes. The promoters of the lamprey Runx genes lack the tandem Runx-binding motifs that are highly conserved among the P1 promoters of gnathostome Runx1, Runx2 and Runx3 genes; instead these promoters contain dispersed single Runx-binding motifs. The 3′UTR of lamprey RunxB contains binding sites for miR-27 and miR-130b/301ab, which are conserved in mammalian Runx1 and Runx3, respectively. Overall, the Runx genes in lamprey seem to have experienced a different evolutionary trajectory from that of gnathostome Runx genes which are highly conserved all the way from cartilaginous fishes to mammals.

show abstract

Section: Resultssupporting

confidence: 62%

Characterization of the Runx Gene Family in a Jawless Vertebrate, the Japanese Lamprey (Lethenteron japonicum)

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Recent data outlined the antagonistic role of RUNX2 in regulating periovulatory gene expression. More specifically, RUNX2 up-regulates the expression of luteal genes, such asRgc32, Mmp13, Ptgds, Fabp6 and Abcb1a, whereas down-regulates the transcription of specific ovulatory genes in luteinizing granulosa cells [12,17]. …”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, in rat ovary Hapln1 expression was affected by both RUNX1 and RUNX2 expression [18], indicating the need for further investigation of RUNX2-RUNX1 interaction in human cumulus cells. Interestingly, RUNX1 transcription was found to be suppressed directly by RUNX2 over-expression in preovulatory granulosa cells, providing another insight of RUNX genes involvement in ovulation [17]. …”

Section: Discussionmentioning

confidence: 99%

Detection of RUNX2 gene expression in cumulus cells in women undergoing controlled ovarian stimulation

Papamentzelopoulou

Mavrogianni

Dinopoulou

et al. 2012

Reprod Biol Endocrinol

View full text Add to dashboard Cite

BackgroundRUNX2 is a transcription factor, whose expression has been recently identified in the mouse ovary. Regulation of RUNX2 expression and its function in the human ovary have not been determined yet. The aim of the present study is the investigation of the possible correlation between RUNX2 gene expression in cumulus cells and controlled ovarian stimulation and pregnancy outcomes after ART treatment.MethodsA total of 41 patients undergoing ICSI treatment for male factor infertility were enrolled into a specific ART program, during which cumulus cells were collected. The expression of RUNX2 gene in cumulus cells was examined by real-time PCR.ResultsConcerning RUNX2 gene expression, 12 out of 41 women were detected with RUNX2 expression, with ratios ranging from 0.84 to 1.00, while 28 out of 41 women had no expression (ratio = 0). Only 1 woman presented a weak RUNX2 gene expression (ratio = 0.52). From 8 women that proceeded to pregnancy, 7 of them did not express RUNX2 gene in cumulus cells, while one was the woman with weak gene expression that also achieved pregnancy. The group of women without RUNX2 expression presented higher number of follicles (p = 0.013), higher number of retrieved oocytes (p = 0.016), higher basal LH serum levels (p = 0.016) and higher peak estradiol levels (p = 0.013), while the number of fertilized oocytes differed marginally between the two groups (p = 0.089). Moreover, RUNX2 expression was negatively associated with LH levels (OR = 0.22, p = 0.021) and E2 levels (OR = 0.25, p = 0.026).ConclusionsConsequently, based on the preliminary findings of the present pilot study a potential inhibitory mechanism of RUNX2 gene is observed in the ovary when high mRNA levels are detected, suggesting that RUNX2 could possibly be used as a candidate genetic marker in the monitoring of the outcome of an ART treatment.

show abstract

“…Moreover, it is known that BMPs affect granulosa cell physiology, among other things also GCs proliferation [20,58]. It is an important question why GCs are so favorable for osteogenic differentiation and it was postulated that this may be related to RUNX2 transcriptional factor, fundamental for osteogenic differentiation [38,86] and up-regulated in the process of GCs luteinization [60].…”

Section: Granulosa Cells and Ability For Transdifferentiationmentioning

confidence: 99%

Plasticity of granulosa cells: on the crossroad of stemness and transdifferentiation potential

Dzafic

Štimpfel

Virant‐Klun

2013

J Assist Reprod Genet

View full text Add to dashboard Cite

The ovarian follicle represents the basic functional unit of the ovary and consists of an oocyte, which is surrounded by granulosa cells (GCs). GCs play an important role in the growth and development of the follicle. They are subject to increased attention since it has recently been shown that the subpopulation of GCs within the growing follicle possesses exceptionally plasticity showing stem cell characteristics. In assisted reproduction programs, oocytes are retrieved from patients together with GCs, which are currently discarded daily, but could be an interesting subject to be researched and potentially used in regenerative medicine in the future. Isolated GCs expressed stem cell markers such as OCT-4, NANOG and SOX-2, showed high telomerase activity, and were in vitro differentiated into other cell types, otherwise not present within ovarian follicles. Recently another phenomenon demonstrated in GCs is transdifferentiation, which could explain many ovarian pathological conditions. Possible applications in regenerative medicine are also given.

show abstract

The role for runt related transcription factor 2 (RUNX2) as a transcriptional repressor in luteinizing granulosa cells

Cited by 24 publications

References 73 publications

Characterization of the Runx Gene Family in a Jawless Vertebrate, the Japanese Lamprey (Lethenteron japonicum)

Characterization of the Runx Gene Family in a Jawless Vertebrate, the Japanese Lamprey (Lethenteron japonicum)

Detection of RUNX2 gene expression in cumulus cells in women undergoing controlled ovarian stimulation

Plasticity of granulosa cells: on the crossroad of stemness and transdifferentiation potential

Contact Info

Product

Resources

About