scholarly journals Participation of transcriptional factor ZBTB16 in the processes of physiological bone tissue formation and in pathological calcification of the aortic valve

2021 ◽  
Vol 10 (4) ◽  
pp. 122-130
Author(s):  
D. S. Semenova ◽  
A. B. Malashicheva
Keyword(s):  
Aortic Valve ◽  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Bone Tissue ◽  
Zinc Finger ◽  
Aortic Valve Stenosis ◽  
Zinc Finger Protein ◽  
Heart Valve Disease ◽  
Binding Motif ◽  
Ectopic Ossification

Degenerative calcific aortic valve stenosis is the most common type of heart valve disease in the Western world. Patients with severe stenosis are associated with 50 percent chance of mortality within two years in the absence of intervention. Surgical interventions are the only treatment method for severe calcific aortic valve stenosis to date. Pharmacological approaches have so far failed to affect the course of the disease. Thus, there is an urgent need to develop novel treatment strategies that could slow down the progression of the stenosis. ZBTB16 is a zinc finger protein with N-term BTB/POZ domain (protein-protein interaction motif) and 9 zinc finger domains (DNA binding motif) in C-term. There is growing evidence proving the participation of ZBTB16 in skeletal development. ZBTB16 has been shown to play a role in the specification of limb and axial skeleton patterning. Moreover, the expression of ZBTB16 is increased in patients with ectopic bone formation. Nowadays, the evidence supports that the mechanisms that play key roles in the formation of bone tissue are similar to the processes occurring during the development of ectopic ossification of the aortic valve. Thus, it can be assumed that ZBTB16 is heavily involved in osteogenic transformation in the aortic valve. Understanding similarities and differences in the mechanisms that mediate osteogenic differentiation of stem cells during bone formation and pathological ossification of tissues can help to find the ways to control the osteogenic differentiation in the human body. The aim of this review is to summarize data on the role of ZBTB16 and its products in the regulation of differentiation and proliferation of cells involved in osteogenesis and in the development of ectopic calcification of the aortic valve. The study of the dynamic changes of ZBTB16 expression in aortic valve calcification is a new and relevant study field.

Zinc-finger protein MdBBX7/MdCOL9, a target of MdMIEL1 E3 ligase, confers drought tolerance in apple

2021 ◽  
Author(s):  
Pengxiang Chen ◽  
Fang Zhi ◽  
Xuewei Li ◽  
Wenyun Shen ◽  
Mingjia Yan ◽  
...  
Keyword(s):  
Drought Stress ◽  
Drought Tolerance ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
E3 Ligase ◽  
26S Proteasome ◽  
Negative Regulator ◽  
Binding Motif ◽  
Ethylene Response Factor ◽  
Finger Protein

Abstract Water deficit is one of the main challenges for apple (Malus × domestica) growth and productivity. Breeding drought-tolerant cultivars depends on a thorough understanding of the drought responses of apple trees. Here, we identified the zinc-finger protein B-BOX 7/CONSTANS-LIKE 9 (MdBBX7/MdCOL9), which plays a positive role in apple drought tolerance. The overexpression of MdBBX7 enhanced drought tolerance, whereas knocking down MdBBX7 expression reduced it. Chromatin immunoprecipitation-sequencing (ChIP-seq) analysis identified one cis-element of MdBBX7, CCTTG, as well as its known binding motif, the T/G box. ChIP-seq and RNA-seq identified 1,197 direct targets of MdBBX7, including ETHYLENE RESPONSE FACTOR (ERF1), EARLY RESPONSIVE TO DEHYDRATION 15 (ERD15), and GOLDEN2-LIKE 1 (GLK1) and these were further verified by ChIP-qPCR and electronic mobility shift assays. Yeast two-hybrid screen identified an interacting protein of MdBBX7, RING-type E3 ligase MYB30-INTERACTING E3 LIGASE 1 (MIEL1). Further examination revealed that MdMIEL1 could mediate the ubiquitination and degradation of MdBBX7 by the 26S proteasome pathway. Genetic interaction analysis suggested that MdMIEL1 acts as an upstream factor of MdBBX7. In addition, MdMIEL1 was a negative regulator of the apple drought stress response. Taken together, our results illustrate the molecular mechanisms by which the MdMIEL1–MdBBX7 module influences the response of apple to drought stress.

Fabrication of 3D plotted scaffold with microporous strands for bone tissue engineering

2020 ◽  
Vol 8 (5) ◽  
pp. 951-960 ◽  
Author(s):  
Ji Min Seok ◽  
Thanavel Rajangam ◽  
Jae Eun Jeong ◽  
Sinyoung Cheong ◽  
Sang Min Joo ◽  
...  
Keyword(s):  
Tissue Engineering ◽  
Bone Formation ◽  
Bone Tissue Engineering ◽  
Osteogenic Differentiation ◽  
Bone Tissue ◽  
Tissue Regeneration ◽  
Cell Attachment ◽  
New Bone Formation

Scaffold porosity has played a key role in bone tissue engineering aimed at effective tissue regeneration, by promoting cell attachment, proliferation, and osteogenic differentiation for new bone formation.

scholarly journals Aortic Valve Stenosis

2020 ◽  
Vol 40 (4) ◽  
pp. 885-900 ◽  
Author(s):  
Philip Roger Goody ◽  
Mohammed Rabiul Hosen ◽  
Dominik Christmann ◽  
Sven Thomas Niepmann ◽  
Andreas Zietzer ◽  
...  
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Immune Cell ◽  
Current Knowledge ◽  
Osteoblastic Differentiation ◽  
Heart Valve Disease ◽  
Interventional Treatment ◽  
High Morbidity ◽  
Aortic Valve Calcification ◽  
Valve Calcification

Aortic valve stenosis is the most prevalent heart valve disease worldwide. Although interventional treatment options have rapidly improved in recent years, symptomatic aortic valve stenosis is still associated with high morbidity and mortality. Calcific aortic valve stenosis is characterized by a progressive fibro-calcific remodeling and thickening of the aortic valve cusps, which subsequently leads to valve obstruction. The underlying pathophysiology is complex and involves endothelial dysfunction, immune cell infiltration, myofibroblastic and osteoblastic differentiation, and, subsequently, calcification. To date, no pharmacotherapy has been established to prevent aortic valve calcification. However, novel promising therapeutic targets have been recently identified. This review summarizes the current knowledge of pathomechanisms involved in aortic valve calcification and points out novel treatment strategies.

Zinc finger protein 521, a new player in bone formation

2010 ◽  
Vol 1192 (1) ◽  
pp. 32-37 ◽  
Author(s):  
Eric Hesse ◽  
Riku Kiviranta ◽  
Meilin Wu ◽  
Hiroaki Saito ◽  
Kei Yamana ◽  
...  
Keyword(s):  
Bone Formation ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Finger Protein

scholarly journals Chaetocin Promotes Osteogenic Differentiation via Modulating Wnt/Beta-Catenin Signaling in Mesenchymal Stem Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Youde Liang ◽  
Xin Liu ◽  
Ruiping Zhou ◽  
Dawei Song ◽  
Yi-Zhou Jiang ◽  
...  
Keyword(s):  
Bone Formation ◽  
Osteogenic Differentiation ◽  
Bone Tissue ◽  
Epigenetic Modification ◽  
Critical Role ◽  
Bone Tissue Regeneration ◽  
Beta Catenin ◽  
Osteogenic Induction

Mesenchymal stemXin cells (MSCs) are a great cell source for bone regeneration. Although combining MSCs with growth factors and scaffolds provides a useful clinical strategy for bone tissue engineering, the efficiency of MSC osteogenic differentiation remains to be improved. Epigenetic modification is related to the differentiation ability of MSCs during osteogenic induction. In this study, we evaluate the effect of Chaetocin, an inhibitor of lysine-specific histone methyltransferases, on the differentiation of MSCs. We found that MSCs treated with Chaetocin demonstrated increased osteogenic ability and reduced adipogenic ability. The expression of osteogenic markers (Runx2 and OPN) was induced in MSCs by Chaetocin during osteogenic induction. Moveover, treatment of Chaetocin in MSCs improves Wnt/β-catenin signaling pathways and its downstream targets. Finally, we showed increased bone formation of MSC and Wnt/β-catenin signaling activity by treatment of Chaetocin using in vivo bone formation assays. Our data uncovered a critical role of Chaetocin in MSC osteogenic differentiation and provide new insights into bone tissue regeneration and repair.

scholarly journals Current Evidence and Future Perspectives on Pharmacological Treatment of Calcific Aortic Valve Stenosis

2020 ◽  
Vol 21 (21) ◽  
pp. 8263 ◽  
Author(s):  
Maristella Donato ◽  
Nicola Ferri ◽  
Maria Giovanna Lupo ◽  
Elisabetta Faggin ◽  
Marcello Rattazzi
Keyword(s):  
Aortic Valve ◽  
Aortic Valve Stenosis ◽  
Current Knowledge ◽  
Present Report ◽  
Lipid Lowering ◽  
Heart Valve Disease ◽  
Current Evidence ◽  
Medical Need ◽  
Health Care Burden ◽  
Lipid Lowering Agents

Calcific aortic valve stenosis (CAVS), the most common heart valve disease, is characterized by the slow progressive fibro-calcific remodeling of the valve leaflets, leading to progressive obstruction to the blood flow. CAVS is an increasing health care burden and the development of an effective medical treatment is a major medical need. To date, no effective pharmacological therapies have proven to halt or delay its progression to the severe symptomatic stage and aortic valve replacement represents the only available option to improve clinical outcomes and to increase survival. In the present report, the current knowledge and latest advances in the medical management of patients with CAVS are summarized, placing emphasis on lipid-lowering agents, vasoactive drugs, and anti-calcific treatments. In addition, novel potential therapeutic targets recently identified and currently under investigation are reported.

scholarly journals Bone morphogenetic protein 9 induces osteogenic differentiation of germ cell 1 spermatogonial cells

2019 ◽  
Author(s):  
Jiye Zhang ◽  
Bangfa Xu ◽  
Xinping Chen ◽  
Liqiang Zhao ◽  
Pei Zhang ◽  
...  
Keyword(s):  
Bone Formation ◽  
Germ Cell ◽  
Osteogenic Differentiation ◽  
Signaling Pathways ◽  
Bone Morphogenetic Protein ◽  
Calcium Deposition ◽  
Ectopic Ossification ◽  
Osteogenic Markers ◽  
Morphogenetic Protein

AbstractGerm cell 1 spermatogonial (GC-1spg) cells are multipotent progenitor cells. We previously confirmed that bone morphogenetic protein (BMP) 9 is among the most osteogenic BMPs. However, whether GC-1spg cells are driven toward osteogenic differentiation under proper stimuli is uncertain. Additionally, the molecular mechanism of BMP9 remains unclear. In the present study, we aimed to determine whether BMP9 can induce osteogenic differentiation of GC-1spg cells. Recombinant adenoviruses were generated by the AdEasy system to regulate the BMP9 expression in GC-1spg cells. We identified osteogenic markers by real-time PCR and staining techniques in vitro. Ectopic ossification assays and histological analysis were also performed to verify the in vivo activity of BMP9. Finally, potential signaling pathways of BMP9 were assessed by transcriptome sequencing and KEGG enrichment analysis. Using recombinant adenoviruses, we demonstrate that BMP9 upregulates osteogenic markers including Runx2, osteocalcin, osteopontin, and Sox9. BMP9 also activates alkaline phosphatase activity and calcium deposition in GC-1spg cells. In vivo results show that BMP9 overexpression in GC-1spg cells promotes ectopic bone formation and chondrogenesis. In addition, RNA-sequencing and KEGG pathway analysis demonstrate that several signaling pathways are involved in BMP9-mediated osteogenesis. GC-1spg cells not only maintain spermatogenesis but also retain the ability to form bone tissue. Therefore, BMP9 activity in GC-1spg cells may help identify signaling pathways implicated in bone formation and could be of use in regenerative medicine.

scholarly journals In vitro identification of DNA-binding motif for the new zinc finger protein AtYY1

2012 ◽  
Vol 44 (6) ◽  
pp. 483-489 ◽  
Author(s):  
Xueping Wu ◽  
Yongsheng Cheng ◽  
Tian Li ◽  
Zhao Wang ◽  
Jin-Yuan Liu
Keyword(s):  
Dna Binding ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Binding Motif ◽  
Finger Protein
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