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.

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.

118. CHARACTERISATION OF HEPARAN SULPHATE PROTEOGLYCANS IN THE MATURING CUMULUS OOCYTE COMPLEX

2009 ◽  
Vol 21 (9) ◽  
pp. 37
Author(s):  
L. N. Watson ◽  
M. Sasseville ◽  
R. B. Gilchrist ◽  
D. L. Russell
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Cell Surface ◽  
Transforming Growth Factor ◽  
Heparan Sulphate ◽  
Cumulus Cells ◽  
Receptor Interaction ◽  
Heparan Sulphate Proteoglycans ◽  
Tgfβ Superfamily

Many growth factors including members of the transforming growth factor beta (TGFβ) superfamily and epidermal growth factor (Egf)-like ligands signal via interactions with heparan sulphate proteoglycans (HSPGs). Cell surface HSPGs can act by sequestering ligands at their site of action, by presenting a ligand to its signalling receptor, or by preventing ligand-receptor interaction. The oocyte secreted factors (OSF) growth differentiation factor 9 and bone morphogenetic protein 15 are members of the TGFβ superfamily that act selectively on cumulus cells. Conversely Egf-like ligands are secreted by mural granulosa cells and transmit LH-induced signals to cumulus cells. We investigated the possibility that HSPGs contribute to the spatially restricted responses these signals exert on cumulus cells. Syndecan-1 and Glypican-1 are cell surface HSPGs that are involved in numerous biological processes, including growth factor regulation, cell proliferation and differentiation. Microarray analysis showed Syndecan-1 and Glypican-1 mRNA expression induced 6-fold (P=10-9) and 3-fold (P=10-7) respectively in Egf+FSH stimulated cumulus oocyte complexes (COCs). Furthermore, Syndecan-1 and Glypican-1 mRNA were induced 27- and 16-fold respectively in COCs after hCG treatment of mice. Syndecan-1 and Glypican-1 protein was localised specifically to the COC through immunohistochemical analysis. In Vitro Maturation (IVM) of oocytes is a valuable alternative to gonadotropin mediated superovulation, but IVM COCs are less competent than those matured in vivo. Several components of the COC have been shown to be altered in IVM, including the chondroitin sulphate proteoglycan Versican. COCs from mice that underwent IVM in the presence of Egf+FSH and cilostamide for 16 hours had >16 fold reduced mRNA for Syndecan-1 when compared with In Vivo matured COCs. The lack of Syndecan-1 in IVM COCs could reduce signalling capacity of growth factors including OSFs. This may contribute to the reduced capacity of IVM oocytes to fertilise and produce a healthy embryo, and ultimately, a healthy offspring.

Comparison of Release Profiles of Various Growth Factors from Biodegradable Carriers

1998 ◽  
Vol 530 ◽  
Author(s):  
Y. Tabata ◽  
M. Yamamoto ◽  
Y. Ikada
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β1 ◽  
The Body ◽  
Bone Morphogenetic Protein 2 ◽  
Biodegradable Hydrogel ◽  
Tgf Β1

AbstractA biodegradable hydrogel was prepared by glutaraldehyde crosslinking of acidic gelatin with an isoelectric point (IEP) of 5.0 as a carrier to release basic growth factors on the basis of polyion complexation. Basic fibroblast growth factor (bFGF), transforming growth factor β1 (TGF-β1), and bone morphogenetic protein-2 (BMP-2) were sorbed from their aqueous solution into the dried gelatin hydrogels to prepare respective growth factor-incorporating hydrogels. Under an in vitro non-degradation condition, approximately 20 % of incorporated bFGF and TGF-β1 was released from the hydrogels within initial 40 min, followed by no further release, whereas a large initial release of BMP-2 was observed. After subcutaneous implantation of the gelatin hydrogels incorporating 125I-labeled growth factor in the mouse back, the remaining radioactivity was measured to estimate the in vivo release profile of growth factors. Incorporation into gelatin hydrogels enabled bFGF and TGF-β1 to retain in the body for about 15 days and the retention period well correlated with that of the gelatin hydrogel. Taken together, it is likely that the growth factors ionically complexed with acidic gelatin were released in vivo as a result of hydrogel biodegradation. On the contrary, basic BMP-2 did not ionically interact with acidic gelatin, resulting in no sustained released by the present biodegradable carrier system.

Growth factor and somatic cell regulation of mouse gonocyte-derived colony formation in vitro

Reproduction ◽  
2000 ◽  
pp. 85-91 ◽  
Author(s):  
S Hasthorpe ◽  
S Barbic ◽  
PJ Farmer ◽  
JM Hutson
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Colony Formation ◽  
Inhibitory Action ◽  
Transforming Growth Factor ◽  
Epidermal Growth ◽  
Growth Factor Beta

At birth, the mouse gonocyte does not resume mitotic activity for several days in vivo but, in an in vitro clonogenic system, cell division commences soon after culture. Somatic testis cell underlays had potent inhibitory activity on gonocyte-derived colony formation (23 +/- 15% compared with 84 +/- 1% in controls; P = 0.0001) when added to cultures of gonocytes in vitro. A Sertoli cell line, TM4B, had an even more pronounced effect on gonocyte clonogenic capacity, with 1 +/- 1% compared with 72 +/- 17% colony formation in controls (P = 0.0003). Testis cells appeared to have a direct inhibitory effect since testis-conditioned medium did not show a significant reduction in the number of colonies. The observed reduction in colony formation with the testis cell underlay was not accounted for by decreased attachment of gonocytes as simultaneous addition of a single cell suspension of testis cells was still effective in significantly reducing colony number when compared with controls (P = 0.01). Therefore, the observed inhibition exerted by testis cells appears to be a consequence of decreased proliferation of gonocytes. Growth factors belonging to the transforming growth factor beta superfamily which are known to be expressed in testis, such as transforming growth factor beta and epidermal growth factor, did not exert any inhibitory action on gonocyte-derived colony formation when added together or alone. However, a shift to a smaller colony size occurred in the presence of transforming growth factor beta and transforming growth factor beta plus epidermal growth factor, indicating a reduction in colony cell proliferation. Evidence for the expression of the Mullerian inhibiting substance receptor on newborn gonocytes using in situ hybridization was inconclusive. This finding was in agreement with the lack of a direct action of Mullerian inhibiting substance on the formation of gonocyte-derived colonies in vitro. Leukaemia inhibitory factor, alone or in combination with forskolin, had neither an inhibitory nor an enhancing effect on gonocyte-derived colony formation. An in vitro clonogenic method to assay for the proliferation of gonocytes in the presence of specific growth factors, cell lines, testis cell underlays and cell suspensions was used to identify a somatic cell-mediated inhibitor which may be responsible for the inhibitory action on gonocyte proliferation in vivo shortly after birth.

scholarly journals Accelerated Bone Healing in Calvarial and Femoral Defects with Injectable Microcarriers that Mimic the Osteogenic Niche

2021 ◽  
Author(s):  
Candice Haase ◽  
Sravani Jaligama ◽  
Eli Mondragon ◽  
Simin Pan ◽  
Eoin H McNeill ◽  
...  
Keyword(s):  
Bone Graft ◽  
Bone Repair ◽  
Bone Growth ◽  
Human Mesenchymal Stem Cells ◽  
Osteogenic Potential ◽  
Gelatin Sponge ◽  
Graft Material ◽  
Cell Matrix ◽  
Calvarial Defects

Osteo-enhanced human mesenchymal stem cells (OEhMSCs) secrete an osteogenic cell matrix (OCM) that mimics the composition of anabolic bone tissue and strongly enhances OEhMSC retention and subsequent bone repair in vivo. Here we demonstrate a system for rapid production of gelatin methacrylate microcarriers coated with decellularized OCM (OCM-GelMA) to serve as an injectable bone graft material with high osteogenic potential comparable to a clinically utilized gold standard, bone morphogenic protein 2 (BMP-2). OEhMSCs seeded onto OCM-GelMA secreted high levels of osteogenic and angiogenic cytokines and expressed higher levels of BMP-2 relative to OEhMSCs on bare GelMA microcarriers. OEhMSCs co-administered with OCM-GelMA microcarriers resulted in enhanced healing of murine critical-sized calvarial defects, which was comparable to that achieved with a BMP-2-laden gelatin sponge control. When tested in a murine femoral defect model, OCM-GelMA co-administered with OEhMSCs also induced profound bone growth within the defect. We submit that OCM-GelMA promotes OEhMSC paracrine release to accelerate bone repair, indicating their potential as a bone graft for use in minimally invasive surgery.

Regulation of DNA synthesis in chicken adipocyte precursor cells by insulin-like growth factors, platelet-derived growth factor and transforming growth factor-β

1991 ◽  
Vol 131 (2) ◽  
pp. 203-209 ◽  
Author(s):  
S. C. Butterwith ◽  
C. Goddard
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Dna Synthesis ◽  
Transforming Growth Factor ◽  
Precursor Cells ◽  
Igf I ◽  
Tgf Β1 ◽  
Adipocyte Precursor ◽  
Insulin Like Growth Factors

ABSTRACT Adipose tissue growth can occur by both hypertrophy and hyperplasia. The capacity for adipocyte hyperplasia in vivo resides in a population of fibroblast-like adipocyte precursor cells but the regulation of the proliferation of these cells by growth factors has not been well characterized. This study was designed to determine the effects of the insulin-like growth factors (IGF-I and IGF-II), platelet-derived growth factor (PDGF) and transforming growth factor-β1 (TGF-β1) added alone or together on the proliferation of primary adipocyte precursor cells in vitro. Adipocyte precursor cell proliferation measured by [3H]thymidine incorporation into DNA was stimulated by all of these growth factors and was particularly marked with PDGF. IGF-I or IGF-II added together with TGF-β1 produced a greater than additive response and the effect of PDGF was synergistic with that of IGF-I at certain concentrations. Stimulation of proliferation of some cell types by TGF-β has been linked to the secondary production of PDGF but the evidence we have suggests that this is unlikely in chicken adipocyte precursors. DNA synthesis in response to TGF-β1 required only a short exposure to the peptide, and conditioned medium from chicken adipocyte precursor cells previously exposed to TGF-β had no effect on DNA synthesis when added to fresh batches of cells. Addition of TGF-β1 together with PDGF produced a synergistic effect whereas an additive effect would be expected if PDGF mediated the effect of TGF-β1. IGF-I mRNA is expressed in the Ob 1771 preadipocyte cell line during differentiation, in stromalvascular cells from adipose tissue, and TGF-β mRNA is expressed in both proliferating and differentiating 3T3-L1 preadipocytes. Together with the data presented here, this would indicate that these peptides have a role in adipocyte development by an autocrine or paracrine mechanism although the source of PDGF in vivo is at present unknown. Journal of Endocrinology (1991) 131, 203–209

scholarly journals Binding of platelet-derived growth factor-BB and transforming growth factor-β 1 to α2-macroglobulin in vitro and in vivo: comparison of receptor-recognized and non-recognized α2-macroglobulin conformations

1993 ◽  
Vol 293 (2) ◽  
pp. 443-450 ◽  
Author(s):  
K P Crookston ◽  
D J Webb ◽  
J Lamarre ◽  
S L Gonias
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Conformational Change ◽  
Electrophoretic Mobility ◽  
Transforming Growth Factor ◽  
Platelet Derived Growth Factor ◽  
Tgf Beta ◽  
Α2 Macroglobulin

alpha 2-Macroglobulin (alpha 2M) undergoes a major conformational change when reacting with proteinases or primary amines. This conformational change has been referred to as the ‘slow’ to ‘fast’ transformation based on the increase in alpha 2M mobility shown by non-denaturing PAGE. Previous studies demonstrated that many cytokines, including transforming growth factor beta 1 (TGF-beta 1) and interleukin-1 beta, bind preferentially or exclusively to alpha 2M which has undergone conformational change. In this study, we demonstrate that platelet-derived growth factor-BB (PDGF-BB) also binds preferentially to conformationally transformed alpha 2M (alpha 2M-methylamine, alpha 2M-trypsin) in vitro. Purified 125I-PDGF-BB-alpha 2M-methylamine complex cleared rapidly from the circulation of mice via the alpha 2M receptor/low-density-lipoprotein-receptor-related protein (alpha 2M-R/LRP). In order to determine whether PDGF-BB or TGF-beta 1 binds to native alpha 2M, we defined the native conformation by lack of interaction with alpha 2M-R/LRP instead of electrophoretic mobility. 125I-PDGF-BB was incubated with 4.3 microM native alpha 2M and 0.47 microM alpha 2M-methylamine. The 125I-PDGF-BB distributed evenly between slow-form and fast-form alpha 2M without shifting the electrophoretic mobility of either species. When the mixed preparation was injected intravenously in mice, 125I-PDGF-BB-fast-form-alpha 2M cleared rapidly and selectively from the circulation; 125I-PDGF-BB which was bound to slow-form alpha 2M was stable in the blood (apparently not recognized by alpha 2M-R/LRP). Therefore, while conformationally transformed alpha 2M binds PDGF-BB preferentially in vitro, non-alpha 2M-R/LRP-recognized alpha 2M binds PDGF-BB as well. Binding of 125I-PDGF-BB and 125I-TGF-beta 1 to alpha 2M was demonstrated in vivo by injecting the free growth factors intravenously into mice. Plasma samples which were subjected to non-denaturing PAGE and autoradiography demonstrated binding of both growth factors exclusively to the slow-form of alpha 2M. Therefore, under normal physiological conditions, native alpha 2M (non-alpha 2M-R/LRP-recognized) is the primary form of the proteinase inhibitor functioning as a carrier of PDGF-BB and TGF-beta 1 in the blood.

Formation of an F2-isoprostane in vascular smooth muscle cells by elevated glucose and growth factors

1996 ◽  
Vol 271 (1) ◽  
pp. H159-H165 ◽  
Author(s):  
R. Natarajan ◽  
L. Lanting ◽  
N. Gonzales ◽  
J. Nadler
Keyword(s):  
Smooth Muscle ◽  
Growth Factors ◽  
Free Radical ◽  
Growth Factor ◽  
Vascular Smooth Muscle ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Vascular Dysfunction ◽  
Elevated Glucose

Recently a series of non-cyclooxygenase-derived prostanoids were identified in vivo in humans and in animal models of free radical injury as products of free radical-catalyzed peroxidation of arachidonic acid. One of these, an F2-isoprostane, 8-epiprostaglandin F2 alpha (8-epi-PGF 2 alpha), is a potent renal vasoconstrictor and can increase vascular smooth muscle cell (VSMC) DNA synthesis. In the present study we have evaluated whether F2-isoprostanes play a role in diabetic vascular dysfunction by studying the formation of 8-epi-PGF2 alpha in porcine VSMC (PVSMC) cultured under hyperglycemic conditions. 8-Epi-PGF2 alpha levels were quantitated by a specific enzyme immunoassay. We also examined whether certain VSMC growth factors, such as angiotensin II, platelet-derived growth factor, and transforming growth factor-beta, could also regulate the formation of 8-epi-PGF2 alpha. We observed that PVSMC cultured under high glucose (HG) conditions produced significantly higher amounts of 8-epi-PGF2 alpha compared with normal glucose (NG) conditions (3.7 +/- 0.13 ng/10(6) cells in HG vs. 2.9 +/- 0.2 ng/10(6) cells in NG, P < 0.05). Furthermore, all three growth factors tested evoked significant dose-dependent formation of 8-epi-PGF2 alpha (ranging from 125 to 220% of control). These results suggest that 8-epi-PGF2 alpha formation, as a result of hyperglycemia or due to growth factor action, may lead to increased VSMC growth and contribute to the complications of diabetes and cardiovascular disease.

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.

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