scholarly journals Links Among Growth Factors, Hormones, and Nuclear Factors With Essential Roles in Bone Formation

2000 ◽  
Vol 11 (4) ◽  
pp. 409-422 ◽  
Author(s):  
Thomas L. McCarthy ◽  
Changhua Ji ◽  
Michael Centrella
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Bone Growth ◽  
Transforming Growth Factor ◽  
Bone Development ◽  
Bone Biology ◽  
Skeletal Tissue ◽  
Osteoblast Lineage

Research performed during the last several years implicates important roles for a variety of growth factors that affect osteoblasts or their precursors during bone development, remodeling, or repair. Of these, three families of growth factors in particular-the transforming growth factor betas (TGF-βs), insulin-like growth factors (IGFs), and bone morphogenetic proteins (BMPs)-are considered to be principal local regulators of osteogenesis, although none is specific for cells of the osteoblast lineage. Therefore, mechanisms to induce skeletal tissue specificity might occur through interactions among these growth factors, with circulating hormones, or through specific intracellular mediators. In the latter case, even more recent studies point to two nuclear transcription factors, termed Core Binding Factor al (CBFal) and CCAAT/Enhancer Binding Protein 8 (C/EBP8), as significant regulators of the expression or activity of specific bone growth factors or their receptors. Perhaps more importantly, events that link these growth factors to nuclear proteins occur in response to glucocorticoids, sex steroids, parathyroid hormone (PTH), or prostaglandin E2 (PGE2), which themselves have well-known effects on bone biology. in this review, we discuss the situations and processes that initially suggested growth-factor- and hormone-specific interactions on cells within the osteoblast lineage, and present evidence for roles that CBFa I and C/EBP8 have on osteoblast function. Finally, we offer examples for how these factors integrate events that are associated with various aspects of bone formation.

scholarly journals PHYSICAL EXERCISE IN THE PROMOTION OF GENE THERAPY AUXILIARY EFFECT

2021 ◽  
Vol 27 (8) ◽  
pp. 779-782
Author(s):  
Wei Shen ◽  
Xiaojun Liang
Keyword(s):  
Gene Therapy ◽  
Growth Factors ◽  
Growth Factor ◽  
Physical Exercise ◽  
Fracture Healing ◽  
Bone Morphogenetic Protein ◽  
Bone Growth ◽  
Transforming Growth Factor ◽  
Transforming Growth Factors ◽  
Morphogenetic Protein

ABSTRACT Introduction: In recent years, genetic engineering has made outstanding contributions to sports, and it has played a huge role in promoting the development of sports-related fields. Objective: We analyze the tissue source of bone growth and healing by studying the role of bone morphogenetic protein and transforming growth factors in fracture injuries caused by sports. Methods: We established a human fracture model to express the shape and content of bone morphogenetic protein and transforming growth factor during fracture healing. Results: In the fracture healing stage caused by different sports, the expression levels of the two genes are different. Bone morphogenetic protein has a high content in the osteogenesis stage of the membrane, while transforming growth factor is high in the cartilage ossification stage. Conclusion: Gene therapy for fractures caused by physical exercise has certain advantages. Osteoblasts and chondrocytes are involved in the synthesis of transforming growth factors. Level of evidence II; Therapeutic studies - investigation of treatment results.

Modulation of growth factor incorporation into ECM of human osteoblast-like cells in vitro by 17 beta-estradiol

1994 ◽  
Vol 267 (6) ◽  
pp. E990-E1001 ◽  
Author(s):  
M. Slater ◽  
J. Patava ◽  
K. Kingham ◽  
R. S. Mason
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Bone Growth ◽  
Transforming Growth Factor ◽  
Bone Matrix ◽  
Tgf Beta ◽  
Subsequent Formation ◽  
Igf I

Human fetal osteoblast-like cells formed a regular multilayered structure in vitro with an extensive collagen-based extracellular matrix. With colloidal gold immunocytochemistry, labels for alkaline phosphatase and osteocalcin were distributed in a relatively diffuse pattern, in contrast to the bone growth factors, insulin-like growth factors I and II (IGF-I and IGF-II), transforming growth factor-beta 1 (TGF-beta 1), and basic fibroblast growth factor, which were colocalized in the collagenous matrix of the multilayer. The inclusion of 17 beta-estradiol (10(-11) to 10(-9) M) in the culture medium increased multilayer depths, increased labeling for IGF-I, IGF-II, and TGF-beta 1, and resulted in earlier detection of TGF-beta 1 label. In contrast, the increase in multilayer depth resulting from treatment with human platelets, an exogenous source of growth factors, was not accompanied by an increase in matrix IGF-I, IGF-II, or TGF-beta 1 label, suggesting a particular effect of estradiol to facilitate this process. Because growth factors in bone matrix may act as coupling agents when released during resorption, reduced growth factor incorporation in the presence of reduced sex steroid concentrations may lead to uncoupling of resorption and subsequent formation.

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.

Bone graft substitutes for the promotion of spinal arthrodesis

2001 ◽  
Vol 10 (4) ◽  
pp. 1-5 ◽  
Author(s):  
Gregory A. Helm ◽  
Hayan Dayoub ◽  
John A. Jane
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Bone Graft ◽  
Bone Repair ◽  
Bone Growth ◽  
Transforming Growth Factor ◽  
Local Bone ◽  
Bone Graft Substitutes ◽  
Autologous Bone

In the prototypical method for inducing spinal fusion, autologous bone graft is harvested from the iliac crest or local bone removed during the spinal decompression. Although autologous bone remains the “gold standard” for stimulating bone repair and regeneration, modern molecular biology and bioengineering techniques have produced unique materials that have potent osteogenic activities. Recombinant human osteogenic growth factors, such as bone morphogenetic proteins, transforming growth factor–β, and platelet-derived growth factor are now produced in highly concentrated and pure forms and have been shown to be extremely potent bone-inducing agents when delivered in vivo in rats, dogs, primates, and humans. The delivery of pluripotent mesenchymal stem cells (MSCs) to regions requiring bone formation is also compelling, and it has been shown to be successful in inducing osteogenesis in numerous pre-clinical studies in rats and dogs. Finally, the identification of biological and nonbiological scaffolding materials is a crucial component of future bone graft substitutes, not only as a delivery vehicle for bone growth factors and MSCs but also as an osteoconductive matrix to stimulate bone deposition directly. In this paper, the currently available bone graft substitutes will be reviewed and the authors will discuss the novel therapeutic approaches that are currently being developed for use in the clinical setting.

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

Osteoinductive effect of soluble transforming growth factor beta receptor 3 on human osteoblast lineage

2021 ◽  
Author(s):  
Angelica Mastandrea Amanso ◽  
Archana Kamalakar ◽  
Sara Bitarafan ◽  
Shelly Abramowicz ◽  
Hicham Drissi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Human Osteoblast ◽  
Beta Receptor ◽  
Growth Factor Beta ◽  
Osteoblast Lineage

scholarly journals Utilizing the ABC Transporter for Growth Factor Production by fleQ Deletion Mutant of Pseudomonas fluorescens

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 679
Author(s):  
Benedict-Uy Fabia ◽  
Joshua Bingwa ◽  
Jiyeon Park ◽  
Nguyen-Mihn Hieu ◽  
Jung-Hoon Ahn
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Pseudomonas Fluorescens ◽  
Abc Transporter ◽  
Transforming Growth Factor Beta ◽  
Deletion Mutant ◽  
Transforming Growth Factor ◽  
Gene Knockout ◽  
Type I ◽  
Double Deletion

Pseudomonas fluorescens, a gram-negative bacterium, has been proven to be a capable protein manufacturing factory (PMF). Utilizing its ATP-binding cassette (ABC) transporter, a type I secretion system, P. fluorescens has successfully produced recombinant proteins. However, besides the target proteins, P. fluorescens also secretes unnecessary background proteins that complicate protein purification and other downstream processes. One of the background proteins produced in large amounts is FliC, a flagellin protein. In this study, the master regulator of flagella gene expression, fleQ, was deleted from P. fluorescens Δtp, a lipase and protease double-deletion mutant, via targeted gene knockout. FleQ directs flagella synthesis, so the new strain, P. fluorescens ΔfleQ, does not produce flagella-related proteins. This not only simplifies purification but also makes P. fluorescens ΔfleQ an eco-friendly expression host because it will not survive outside a controlled environment. Six recombinant growth factors, namely, insulin-like growth factors I and II, beta-nerve growth factor, fibroblast growth factor 1, transforming growth factor beta, and tumor necrosis factor beta, prepared using our supercharging method, were successfully secreted by P. fluorescens ΔfleQ. Our findings demonstrate the potential of P. fluorescens ΔfleQ, combined with our supercharging process, as a PMF.

Mechanisms of renal tubular cell hypertrophy: mitogen-induced suppression of proteolysis

1997 ◽  
Vol 273 (3) ◽  
pp. C843-C851 ◽  
Author(s):  
H. A. Franch ◽  
P. V. Curtis ◽  
W. E. Mitch
Keyword(s):  
Protein Synthesis ◽  
Growth Factors ◽  
Growth Factor ◽  
Protein Degradation ◽  
Transforming Growth Factor ◽  
Primary Cultures ◽  
Renal Tubular Cell ◽  
Kidney Cells ◽  
Tgf Beta ◽  
Lysosomal Proteolysis

The combination of epidermal growth factor (EGF) plus transforming growth factor-beta 1 (TGF-beta 1) causes hypertrophy in renal epithelial cells. One mechanism contributing to hypertrophy is that EGF induces activation of the cell cycle and increases protein synthesis, whereas TGF-beta 1 prevents cell division, thereby converting hyperplasia to hypertrophy. To assess whether suppression of proteolysis is another mechanism causing hypertrophy induced by these growth factors, we measured protein degradation in primary cultures of proximal tubule cells and in cultured NRK-52E kidney cells. A concentration of 10(-8) M EGF alone or EGF plus 10(-10) M TGF-beta 1 decreased proteolysis by approximately 30%. TGF-beta 1 alone did not change protein degradation. Using inhibitors, we examined which proteolytic pathway is suppressed. Neither proteasome nor calpain inhibitors prevented the antiproteolytic response to EGF + TGF-beta 1. Inhibitors of lysosomal proteases eliminated the antiproteolytic response to EGF + TGF-beta 1, suggesting that these growth factors act to suppress lysosomal proteolysis. This antiproteolytic response was not caused by impaired EGF receptor signaling, since lysosomal inhibitors did not block EGF-induced protein synthesis. We conclude that suppression of lysosomal proteolysis contributes to growth factor-mediated hypertrophy of cultured kidney cells.

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