Possible Roles of Bone Morphogenetic Proteins and Transforming Growth Factor-βs in the Pathogenesis of OPLL and OLF

OPLL ◽  
2007 ◽  
pp. 59-63 ◽  
Author(s):  
Hideki Yoshikawa
Keyword(s):  
Growth Factor ◽  
Bone Morphogenetic Proteins ◽  
Transforming Growth Factor

Bone Morphogenetic Proteins and Their Receptors in the Eye

2007 ◽  
Vol 232 (8) ◽  
pp. 979-992 ◽  
Author(s):  
Robert J. Wordinger ◽  
Abbot F. Clark
Keyword(s):  
Growth Factor ◽  
Bone Morphogenetic Proteins ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Bmp Signaling ◽  
Receptor Expression ◽  
Future Research ◽  
Cellular Functions ◽  
Ocular Tissues ◽  
Bmp Receptors

The human genome encodes at least 42 different members of the transforming growth factor-β superfamily of growth factors. Bone morphogenetic proteins (BMPs) are the largest subfamily of proteins within the transforming growth factor-β superfamily and are involved in numerous cellular functions including development, morphogenesis, cell proliferation, apoptosis, and extracellular matrix synthesis. This article first reviews BMPs and BMP receptors, BMP signaling pathways, and mechanisms controlling BMP signaling. Second, we review BMP and BMP receptor expression during embryonic ocular development/ differentiation and in adult ocular tissues. Lastly, future research directions with respect to BMP, BMP receptors, and ocular tissues are suggested.

scholarly journals Eps15R is required for bone morphogenetic protein signalling and differentially compartmentalizes with Smad proteins

Open Biology ◽  
2012 ◽  
Vol 2 (4) ◽  
pp. 120060 ◽  
Author(s):  
Elizabeth M. Callery ◽  
Chong Yon Park ◽  
Xin Xu ◽  
Haitao Zhu ◽  
James C. Smith ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Morphogenetic Proteins ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Adaptor Protein ◽  
Transforming Growth Factor Β ◽  
Morphogenetic Protein ◽  
Smad Proteins ◽  
Epidermal Growth ◽  
Bmp Signalling

Transforming growth factor β superfamily members signal through Smad transcription factors. Bone morphogenetic proteins (BMPs) act via Smads 1, 5 and 8 and TGF-βs signal through Smads 2 and 3. The endocytic adaptor protein Eps15R, or ‘epidermal growth factor (EGF) receptor pathway substrate 15-related protein’ is a component of EGF signal transduction, mediating internalization of the EGF receptor. We show that it interacts with Smad proteins, is required for BMP signalling in animal caps and stimulates Smad1 transcriptional activity. This function resides in the Asp-Pro-Phe motif-enriched ‘DPF domain’ of Eps15R, which activates transcription and antagonizes Smad2 signalling. In living cells, Eps15R segregates into spatially distinct regions with different Smads, indicating an unrecognized level of Smad compartmentalization.

scholarly journals The N domain of Smad7 is essential for specific inhibition of transforming growth factor-β signaling

2001 ◽  
Vol 155 (6) ◽  
pp. 1017-1028 ◽  
Author(s):  
Aki Hanyu ◽  
Yasuhiro Ishidou ◽  
Takanori Ebisawa ◽  
Tomomasa Shimanuki ◽  
Takeshi Imamura ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Morphogenetic Proteins ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Amino Acid Sequences ◽  
Bmp Signaling ◽  
Type I ◽  
Specific Inhibition ◽  
Amino Terminal ◽  
Carboxy Terminal

Inhibitory Smads (I-Smads) repress signaling by cytokines of the transforming growth factor-β (TGF-β) superfamily. I-Smads have conserved carboxy-terminal Mad homology 2 (MH2) domains, whereas the amino acid sequences of their amino-terminal regions (N domains) are highly divergent from those of other Smads. Of the two different I-Smads in mammals, Smad7 inhibited signaling by both TGF-β and bone morphogenetic proteins (BMPs), whereas Smad6 was less effective in inhibiting TGF-β signaling. Analyses using deletion mutants and chimeras of Smad6 and Smad7 revealed that the MH2 domains were responsible for the inhibition of both TGF-β and BMP signaling by I-Smads, but the isolated MH2 domains of Smad6 and Smad7 were less potent than the full-length Smad7 in inhibiting TGF-β signaling. The N domains of I-Smads determined the subcellular localization of these molecules. Chimeras containing the N domain of Smad7 interacted with the TGF-β type I receptor (TβR-I) more efficiently, and were more potent in repressing TGF-β signaling, than those containing the N domain of Smad6. The isolated N domain of Smad7 physically interacted with the MH2 domain of Smad7, and enhanced the inhibitory activity of the latter through facilitating interaction with TGF-β receptors. The N domain of Smad7 thus plays an important role in the specific inhibition of TGF-β signaling.

The induction of bone formation: From bone morphogenetic proteins to the transforming growth factor-β3 protein - Redundancy, pleiotropy and the induction of cementogenesis

2021 ◽  
Vol 76 (06) ◽  
pp. 331-356
Author(s):  
Ugo Ripamont
Keyword(s):  
Growth Factor ◽  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Transforming Growth Factor ◽  
Alveolar Bone ◽  
Transforming Growth Factor Β ◽  
Periodontal Tissue ◽  
Rapid Induction ◽  
Furcation Defects ◽  
Expression Pathways

This review proposes to translate organogenesis and the induction of bone formation by the recombinant human transforming growth factor-β3 (hTGF-β3 ) in the Chacma baboon Papio ursinus to periodontal tissue induction and regeneration. Naturally derived highly purified osteogenic proteins of the transforming growth factor-β (TGF-β) supergene family were implanted in Class II furcation defects of the first and second mandibular molars. Additional defects in P.ursinus were treated with recombinant human osteogenic protein-1 (hOP-1, also known as bone morphogeneticprotein-7, hBMP-7) and hBMP-2, singly or in binary applications. In different studies defects were also implanted with hTGF-β3singly or in binary application with hOP-1. Harvested specimens on day 60 and 180 were processed for undecalcified histology using tungsten-carbide knives mounted on Polycut sledge’ micro-tomes or the Exakt precision cutting and grinding system.Highly purified osteogenic proteins showed the induction of Sharpey’s fibres into newly formed cementoid with foci of mineralization. hOP-1 induced substantial cementogenesis whilst hBMP-2 preferentially induced alveolar bone. Intramuscular implantation of hTGF-β3 absorbed onto coral-derived macroporous bioreactors engineered large heterotopic multicellular bone organoids. Gene expression pathways by quantitative Reverse Transcription Polymerases Chain Reaction (qRT-PCR) show that the induction of bone is via several profiled BMPs and TGF-βs expressed upon implantation of hTGF-β3 recapitulating the synergistic induction of bone as shown by binary applications of low doses of hTGF-β1 and hTGF-β3with hOP-1. The rapid induction of bone by hTGF-β3 provides theframework for a paradigmatic shift from recombinanthBMPs to hTGF-β3 in clinical contexts, provocatively operational in periodontal tissue regeneration with substantial induction of cementogenesis in angiogenesis.

Profiling bone morphogenetic proteins and transforming growth factor-βs by hTGF-β3 pre-treated coral-derived macroporous bioreactors: The power of one

Biomaterials ◽  
2015 ◽  
Vol 49 ◽  
pp. 90-102 ◽  
Author(s):  
Ugo Ripamonti ◽  
Thérèse Dix-Peek ◽  
Ruqayya Parak ◽  
Brenda Milner ◽  
Raquel Duarte
Keyword(s):  
Growth Factor ◽  
Bone Morphogenetic Proteins ◽  
Transforming Growth Factor

Metaplastic Bone Formation in Nasal Polyps with Histologic Presence of Transforming Growth Factor β-1 (TGFβ-1) and Bone Morphogenetic Proteins (BMPs)

2001 ◽  
Vol 125 (1) ◽  
pp. 96-97 ◽  
Author(s):  
Jeffrey M. Bumpous ◽  
Andrew A. Jacono ◽  
Anthony P. Sclafani ◽  
Thomas Van De Water ◽  
Steven McCormick ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Nasal Polyps ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Metaplastic Bone

scholarly journals Transforming growth factor-β signaling in hypertensive remodeling of porcine aorta

2009 ◽  
Vol 297 (6) ◽  
pp. H2044-H2053 ◽  
Author(s):  
Natasa Popovic ◽  
Eric A. Bridenbaugh ◽  
Jessemy D. Neiger ◽  
Jin-Jia Hu ◽  
Marina Vannucci ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Bone Morphogenetic Proteins ◽  
Vascular Remodeling ◽  
Transforming Growth Factor ◽  
Regulation Of Gene Expression ◽  
Transforming Growth Factor Β ◽  
Altered Expression ◽  
Protein Levels ◽  
Extracellular Region

A porcine aortic coarctation model was used to examine regulation of gene expression in early hypertensive vascular remodeling. Aortic segments were collected proximal (high pressure) and distal (low pressure) to the coarctation after 2 wk of sustained hypertension (mean arterial pressure > 150 mmHg). Porcine 10K oligoarrays used for gene expression profiling of the two regions of aorta revealed downregulation of cytoskeletal and upregulation of extracellular region genes relative to the whole genome. A genomic database search for transforming growth factor-β (TGF-β) control elements showed that 19% of the genes that changed expression due to hypertension contained putative TGF-β control elements. Real-time RT-PCR and microarray analysis showed no change in expression of TGF-β1, TGF-β2, TGF-β3, or bone morphogenetic proteins-2 and -4, yet immunohistochemical staining for phosphorylated SMAD2, an indicator of TGF-β signaling, and for phosphorylated SMAD1/5/8, an indicator of signaling through the bone morphogenetic proteins, showed the highest percentage of positively stained cells in the proximal aortic segments of occluded animals. For TGF-β signaling, this increase was significantly different than for sham-operated controls. Western blot analysis showed no difference in total TGF-β1 protein levels with respect to treatment or aortic segment. Immunohistochemistry showed that the protein levels of latency-associated peptide was decreased in proximal segments of occluded animals. Collectively, these results suggest that activation of TGF-β, but not altered expression, may be a major mechanism regulating early hypertensive vascular remodeling.

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