scholarly journals Effect of a Bone Morphogenetic Protein-2-derived peptide on the expression of tumor marker ZNF217 in osteoblasts and MCF-7 cells

2020 ◽  
Author(s):  
Aglaia Mantsou ◽  
Paraskevas Lamprou ◽  
Stylianos Zafeirios Karoulias ◽  
Rigini Papi ◽  
Theodora Choli-Papadopoulou
Keyword(s):  
Bone Morphogenetic Protein ◽  
Breast Cancer Cells ◽  
Zinc Finger Protein ◽  
Breast Tumors ◽  
Bmp Signaling ◽  
Bone Morphogenetic Protein 2 ◽  
Mrna Levels ◽  
Finger Protein ◽  
Morphogenetic Protein ◽  
Mcf 7

Abstract Zinc Finger Protein 217 (ZNF217), a transcription factor and oncogene product, has been found to dysregulate Bone Morphogenetic Protein (BMP) signaling and induce invasion in breast tumors. In this study, the effect of BMP-2 or an active BMP-2 peptide, AISMLYLDEN, on the expression of ZNF217, BMP4 and CDK-inhibitor p21 gene, CDKN1A, was investigated in DPSCs during osteogenic differentiation and in MCF-7 breast cancer cells. BMP-2 peptide reduced the expression of ZNF217 during the first two weeks of osteogenesis and increased the expression of CDKN1A after three weeks. BMP-2 and BMP-2 peptide increased the expression of BMP4 during the first week. The same genes were monitored in MCF-7 after treatment with BMP-2 or different concentrations of BMP-2 peptide. CDKN1A mRNA levels were 10-, 8- and 6-fold higher respectively in MCF-7 cells treated with BMP-2 (100 ng/ml) or BMP-2 peptide (45.2 and 22.6 ng/ml) than in untreated MCF-7. BMP-2 peptide, at a concentration of 22.6 ng/ml reduced ZNF217 expression after 6 h and 12 h. BMP-2 reduced BMP4 expression to undetected levels within 24 h. At appropriate concentrations, BMP-2 and the peptide AISMLYLDEN can be considered as a possible novel therapeutic method in breast tumors with a metastatic tendency to the bones.

scholarly journals Post-Transcriptional Bone Morphogenetic Protein 2 (BMP2) Gene Regulation in Aorta

2019 ◽  
Author(s):  
Tapan A. Shah ◽  
Ying Tang ◽  
Edward J. Yurkow ◽  
Melissa B. Rogers
Keyword(s):  
Bone Morphogenetic Protein ◽  
Kidney Function ◽  
Bmp Signaling ◽  
Bone Morphogenetic Protein 2 ◽  
Heart Weight ◽  
Mrna Levels ◽  
Conserved Sequence ◽  
Morphogenetic Protein ◽  
Healthy Control ◽  
The Impact

AbstractDeletion of an “ultra-conserved sequence” (UCS) within the Bone Morphogenetic Protein (Bmp)2 mRNA previously revealed that the sequence represses Bmp2 reporter gene expression in vascular cells. The objective was to determine the impact of the endogenous UCS on Bmp2 mRNA levels, BMP signaling, and calcification in the healthy control aorta and in the calcified aorta of mice with renal disease. We compared the phenotypes of mice bearing a wild type Bmp2 allele or the UCS deletion allele in mice with normal kidney function or in Klotho mutant mice with reduced kidney function. BMP signaling and calcium levels were normally higher in control females relative to males. UCS deletion induced aortic Bmp2 mRNA and BMP signaling in control males, but not in females. UCS deletion significantly increased BMP signaling in both male and female Klotho homozygotes. Inheritance of the Bmp2 UCS deletion and Klotho alleles was skewed from Mendelian expectations suggesting that these alleles influence interacting pathways. Analyses of body and heart weight supported these interactions. The Bmp2 UCS represses BMP signaling in control males and in mice of both sexes with abnormal mineralization associated with kidney disease. Disease and sex-specific differences in Bmp2 gene control may influence the onset and progression of cardiovascular diseases.

scholarly journals Up-regulation of bone morphogenetic protein and its signaling molecules following castration of bulls and their association with intramuscular fat content in Korean cattle

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Da Jin Sol Jung ◽  
Myunggi Baik
Keyword(s):  
Bone Morphogenetic Protein ◽  
Signaling Pathway ◽  
Muscle Fiber ◽  
Fiber Type ◽  
Glycolytic Enzyme ◽  
Bmp Signaling ◽  
Muscle Fiber Type ◽  
Mrna Levels ◽  
Korean Cattle ◽  
Morphogenetic Protein

AbstractWe evaluated whether castration affects bone morphogenetic protein 2 (BMP2) level and the expression of its signaling molecules in Korean cattle bulls. We also checked whether castration affects the expression of muscle fiber type and oxidative and glycolytic enzyme genes. Enzyme-linked immunosorbent assays revealed that steers had higher plasma BMP2 and leptin concentrations than bulls. Quantitative real-time PCR showed that steers had higher mRNA levels of the lysyl oxidase gene, a downstream target of the BMP signaling pathway, in the longissimus thoracis (LT) muscle. Steers had higher adipogenic peroxisome proliferator-activated receptor gamma and lipogenic fatty acid binding protein 4 mRNA levels in the LT than bulls. Steers had lower mRNA levels for several muscle fiber type 1 genes and fiber type 2A myosin heavy chain 2 gene than bulls. Steers had higher mRNA levels of the glycolytic enzyme phosphoglycerate kinase 1 gene than bulls. Transcript levels of oxidative enzyme genes did not differ between bulls and steers. Regression analysis revealed a positive association between plasma BMP2 levels and intramuscular fat (IMF) content in the steer group. These findings suggest that upregulation of the BMP signaling pathway in response to castration induces increased adipogenic gene expression, contributing to the increased IMF deposition observed in castrated animals.

Bone Morphogenetic Protein-2 Inhibits Differentiation and Mineralization of Cementoblasts in vitro

2003 ◽  
Vol 82 (1) ◽  
pp. 23-27 ◽  
Author(s):  
M. Zhao ◽  
J.E. Berry ◽  
M.J. Somerman
Keyword(s):  
Bone Morphogenetic Protein ◽  
Type I Collagen ◽  
Bone Morphogenetic Protein 2 ◽  
Nodule Formation ◽  
Type I ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Morphogenetic Protein ◽  
Regenerative Therapies

As an approach for improving the outcome and predictability of periodontal regenerative therapies, we have focused on determining the responses of cells within the local environment to putative regenerative factors. This study examined the effects of bone morphogenetic protein-2 (BMP-2) on murine cementoblasts in vitro. Northern blot analysis indicated that BMP-2 decreased mRNA levels of bone sialoprotein and type I collagen dose-dependently (10–300 ng/mL). At low doses, up to 100 ng/mL, BMP-2 had no effect on transcripts for osteocalcin and osteopontin, whereas at 300 ng/mL, BMP-2 greatly increased expression of these two genes. BMP-2 also inhibited cementoblast-mediated mineral nodule formation in a dose-dependent manner (inhibition was noted at 10 ng/mL). Noggin reversed the effects of BMP-2 on gene expression and on mineralization. These findings reflect the diverse responses of periodontal cells to BMP-2 and highlight the need to consider the complexity of factors involved in designing predictable regenerative therapies.

scholarly journals Is NO the Answer? The Nitric Oxide Pathway Can Support Bone Morphogenetic Protein 2 Mediated Signaling

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1273 ◽  
Author(s):  
Christopher Differ ◽  
Franka Klatte-Schulz ◽  
Nicole Bormann ◽  
Susann Minkwitz ◽  
Petra Knaus ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Fracture Healing ◽  
Bone Morphogenetic Protein ◽  
Clinical Importance ◽  
Bmp Signaling ◽  
Bone Morphogenetic Protein 2 ◽  
Type I ◽  
Positive Effects ◽  
Morphogenetic Protein

The growth factor bone morphogenetic protein 2 (BMP2) plays an important role in bone development and repair. Despite the positive effects of BMP2 in fracture healing, its use is associated with negative side effects and poor cost effectiveness, partly due to the large amounts of BMP2 applied. Therefore, reduction of BMP2 amounts while maintaining efficacy is of clinical importance. As nitric oxide (NO) signaling plays a role in bone fracture healing and an association with the BMP2 pathway has been indicated, this study aimed to investigate the relationship of BMP2 and NO pathways and whether NO can enhance BMP2-induced signaling and osteogenic abilities in vitro. To achieve this, the stable BMP reporter cell line C2C12BRELuc was used to quantify BMP signaling, and alkaline phosphatase (ALP) activity and gene expression were used to quantify osteogenic potency. C2C12BRELuc cells were treated with recombinant BMP2 in combination with NO donors and substrate (Deta NONOate, SNAP & L-Arginine), NOS inhibitor (LNAME), soluble guanylyl cyclase (sGC) inhibitor (LY83583) and activator (YC-1), BMP type-I receptor inhibitor (LDN-193189), or protein kinase A (PKA) inhibitor (H89). It was found that the NOS enzyme, direct NO application, and sGC enhanced BMP2 signaling and improved BMP2 induced osteogenic activity. The application of a PKA inhibitor demonstrated that BMP2 signaling is enhanced by the NO pathway via PKA, underlining the capability of BMP2 in activating the NO pathway. Collectively, this study proves the ability of the NO pathway to enhance BMP2 signaling.

scholarly journals Effect of a Bone Morphogenetic Protein-2-derived peptide on the expression of tumor marker ZNF217 in osteoblasts and MCF-7 cells

Bone Reports ◽  
2021 ◽  
pp. 101125
Author(s):  
Aglaia Mantsou ◽  
Maria Pitou ◽  
Eleni Papachristou ◽  
Rigini M. Papi ◽  
Paraskevas Lamprou ◽  
...  
Keyword(s):  
Tumor Marker ◽  
Bone Morphogenetic Protein ◽  
Bone Morphogenetic Protein 2 ◽  
Morphogenetic Protein ◽  
Mcf 7

scholarly journals Functional Differentiation of Uterine Stromal Cells Involves Cross-Regulation between Bone Morphogenetic Protein 2 and Krüppel-Like Factor (KLF) Family Members KLF9 and KLF13

Endocrinology ◽  
2010 ◽  
Vol 151 (7) ◽  
pp. 3396-3406 ◽  
Author(s):  
John Mark P. Pabona ◽  
Zhaoyang Zeng ◽  
Frank A. Simmen ◽  
Rosalia C. M. Simmen
Keyword(s):  
Bone Morphogenetic Protein ◽  
Stromal Cells ◽  
Functional Differentiation ◽  
Bone Morphogenetic Protein 2 ◽  
Mrna Levels ◽  
Uterine Receptivity ◽  
Endometrial Stromal Cells ◽  
Interacting Protein ◽  
Morphogenetic Protein ◽  
Implantation Success

The inability of the uterine epithelium to enter a state of receptivity for the embryo to implant is a significant underlying cause of early pregnancy loss. We previously showed that mice null for the progesterone receptor (PGR)-interacting protein Krüppel-like factor (KLF) 9 are subfertile and exhibit reduced uterine progesterone sensitivity. KLF9 expression is high in predecidual stroma, undetectable in decidua, and enhanced in uteri of mice with conditional ablation of bone morphogenetic protein 2 (BMP2). Given the individual importance of KLF9 and BMP2 for implantation success, we hypothesized that the establishment of uterine receptivity involves KLF9 and BMP2 functional cross-regulation. To address this, we used early pregnant wild-type and Klf9 null mice and KLF9 small interfering RNA-transfected human endometrial stromal cells (HESCs) induced to differentiate under standard conditions. Loss of KLF9 in mice and HESCs enhanced BMP2 expression, whereas recombinant BMP2 treatment of HESCs attenuated KLF9 mRNA levels. IGFBP1 and KLF9-related KLF13 expression were positively associated with BMP2 and inversely associated with KLF9. Prolonged, but not short-term, knockdown of KLF9 in HESCs reduced IGFBP1 expression. Mouse uterine Igfbp1 expression was similarly reduced with Klf9 ablation. PGR-A and PGR-B expression were positively associated with KLF9 in predecidual HESCs but not decidualizing HESCs. KLF13 knockdown attenuated BMP2 and PGR-B and abrogated BMP2-mediated inhibition of KLF9 expression. Results support cross-regulation among BMP2, KLF9, and KLF13 to maintain progesterone sensitivity in stromal cells undergoing differentiation and suggest that loss of this regulatory network compromises establishment of uterine receptivity and implantation success.

scholarly journals Bone morphogenetic protein 2 inhibits growth differentiation factor 8-induced cell signaling via upregulation of gremlin2 expression in human granulosa-lutein cells

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xiaoyan Luo ◽  
Hsun-Ming Chang ◽  
Yuyin Yi ◽  
Yingpu Sun ◽  
Peter C. K. Leung
Keyword(s):  
Bone Morphogenetic Protein ◽  
Molecular Mechanisms ◽  
Kinase Inhibitors ◽  
Bmp Signaling ◽  
Bone Morphogenetic Protein 2 ◽  
Type I ◽  
Dependent Manner ◽  
Small Interfering Rnas ◽  
Differentiation Factor ◽  
Morphogenetic Protein

Abstract Background Bone morphogenetic protein 2 (BMP2), growth differentiation factor 8 (GDF8) and their functional receptors are expressed in human ovarian follicles, and these two intrafollicular factors play essential roles in regulating follicle development and luteal function. As BMP antagonists, gremlin1 (GREM1) and gremlin2 (GREM2) suppress BMP signaling through blockage of ligand-receptor binding. However, whether BMP2 regulates the expression of GREM1 and GREM2 in follicular development remains to be determined. Methods In the present study, we investigated the effect of BMP2 on the expression of GREM1 and GREM2 and the underlying mechanisms in human granulosa-lutein (hGL) cells. An established immortalized human granulosa cell line (SVOG) and primary hGL cells were used as study models. The expression of GREM1 and GREM2 were examined following cell incubation with BMP2 at different concentrations and time courses. The TGF-β type I inhibitors (dorsomorphin, DMH-1 and SB431542) and small interfering RNAs targeting ALK2, ALK3, SMAD2/3, SMAD1/5/8 and SMAD4 were used to investigate the involvement of the SMAD-dependent pathway. Results Our results showed that BMP2 significantly increased the expression of GREM2 (but not GREM1) in a dose- and time-dependent manner. Using a dual inhibition approach combining kinase inhibitors and siRNA-mediated knockdown, we found that the BMP2-induced upregulation of GREM2 expression was mediated by the ALK2/3-SMAD1/5-SMAD4 signaling pathway. Moreover, we demonstrated that BMP2 pretreatment significantly attenuated the GDF8-induced phosphorylation of SMAD2 and SMAD3, and this suppressive effect was reversed by knocking down GREM2 expression. Conclusions Our findings provide new insight into the molecular mechanisms by which BMP2 modulates the cellular activity induced by GDF8 through the upregulated expression of their antagonist (GREM2).

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