TRANSFORMING GROWTH FACTOR-??3 STIMULATES PROTEOGLYCAN AND COLLAGEN SYNTHESIS UNDER LOW OXYGEN TENSION BY BOVINE INTERVERTEBRAL DISC CELLS IN ALGINATE BEADS

Spine ◽  
2008 ◽  
Vol &NA; ◽  
pp. 52
Author(s):  
Yumiko Abe ◽  
Kunihiro Asanuma ◽  
Hitoshi Tonomura ◽  
Tomoatsu Kimura
Keyword(s):  
Growth Factor ◽  
Intervertebral Disc ◽  
Oxygen Tension ◽  
Collagen Synthesis ◽  
Transforming Growth Factor ◽  
Alginate Beads ◽  
Low Oxygen ◽  
Low Oxygen Tension ◽  
Disc Cells

scholarly journals Low Oxygen Tension Modulates the Insulin-Like Growth Factor-1 or -2 Signaling via Both Insulin-Like Growth Factor-1 Receptor and Insulin Receptor to Maintain Stem Cell Identity in Placental Mesenchymal Stem Cells

Endocrinology ◽  
2016 ◽  
Vol 157 (3) ◽  
pp. 1163-1174 ◽  
Author(s):  
Amer Youssef ◽  
Victor K. M. Han
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Growth Factor ◽  
Insulin Receptor ◽  
Oxygen Tension ◽  
Insulin Like Growth Factor ◽  
Low Oxygen ◽  
Placental Mesenchymal Stem Cells ◽  
Low Oxygen Tension

Abstract Placental mesenchymal stem cells (PMSCs) are readily available multipotent stem cells for potential use in regenerative therapies. For this purpose, PMSCs must be maintained in culture conditions that mimic the in vivo microenvironment. IGFs (IGF-1 and IGF-2) and oxygen tension are low in the placenta in early gestation and increase as pregnancy progresses. IGFs bind to two receptor tyrosine kinases, the IGF-1 receptor (IGF-1R) and the insulin receptor (IR), and their hybrid receptors. We hypothesized that IGF-1 and IGF-2 signal via distinct signaling pathways under low-oxygen tension to maintain PMSC multipotency. In preterm PMSCs, low-oxygen tension increased the expression of IGF-2 and reduced IGF-1. IGF-1 stimulated higher phosphorylation of IGF-1Rβ, ERK1/2, and AKT, which was maintained at steady lower levels by low oxygen tension. PMSC proliferation was increased by IGF-1 more than IGF-2,and was potentiated by low-oxygen tension. This IGF/low oxygen tension-mediated proliferation was receptor dependent because neutralization of the IGF-1R inhibited PMSC proliferation in the presence of IGF-1 and the IR in presence of IGF-2. These findings suggest that both IGF-1R and the IR can participate in mediating IGF signaling in maintaining PMSCs multipotency. We conclude that low-oxygen tension can modify the IGF-1 or IGF-2 signaling via the IGF-1R and IR in PMSCs.

scholarly journals Growth and Differentiation Factor-5 Contributes to the Structural and Functional Maintenance of the Intervertebral Disc

2015 ◽  
Vol 35 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Chencheng Feng ◽  
Huan Liu ◽  
Yang Yang ◽  
Bo Huang ◽  
Yue Zhou
Keyword(s):  
Stem Cell ◽  
Growth Factors ◽  
Growth Factor ◽  
Intervertebral Disc ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Differentiation Factor ◽  
Disc Cells ◽  
Growth Factor Genes ◽  
Gene Defects

Intervertebral disc degeneration (IDD) is a widely recognized contributor to low back pain (LBP). The Prevention or reversal of IDD is a potential treatment for LBP. Unfortunately, current treatments for IDD are aimed at relieving symptoms rather than regenerating disc structure or function. Recently, the injection of growth factors and mesenchymal stem cell (MSC) transplantation have been shown to be promising biological therapies for IDD. Growth factors stimulate the proliferation of and matrix synthesis by intervertebral disc (IVD) cells, leading to the regeneration of degenerative discs. Growth factors, hypoxia and co-culture with nucleus pulposus (NP) cells induce MSCs to differentiate toward an NP-like phenotype, which can increase the number of functional cells in the IVD or enhance the function of endogenous disc cells to facilitate IVD regeneration. Therefore, the emerging roles of growth factors in IVD regeneration have piqued the interest of researchers. Growth factors including transforming growth factor-β (TGF-β), fibroblast growth factor (FGF), insulin-like growth factor-1 (IGF-1) and growth and differentiation factor-5 (GDF-5), among others, have been demonstrated to enhance anabolism in IVD cells and to induce NP-like differentiation of MSCs. However, the injection of TGF, IGF and FGF into human IVDs may induce unwanted blood vessel ingrowth, which accelerates the process of IDD, the injection of GDF-5 may not have the same effect. This finding suggests that GDF-5 is a preferable growth factor for use in IDD treatment compared with TGF, IGF and FGF. The GDF-5 gene is one of the few growth factor genes that have been found to be associated with IDD thus far; moreover, the GDF-5 gene defects lead to collagen and proteoglycan abnormalities in discs in mice, suggesting that GDF-5 contributes to the structural and functional maintenance of the IVD. This review is focused on the functions of GDF-5 in the IVD and on the association between GDF-5 and a genetic predisposition to IDD. The effects of GDF-5 on IVD regeneration and on MSC differentiation are also discussed. GDF-5 plays a crucial role in the pathogenesis of IDD and is a promising therapeutic agent for IDD. Additionally, stem cell transplantation has been shown to be a promising biological therapy for IDD.

scholarly journals Platelet-derived growth factor (PDGF) and PDGF receptors in rat corpus cavernosum: changes in expression after transient in vivo hypoxia

2001 ◽  
Vol 170 (2) ◽  
pp. 395-402 ◽  
Author(s):  
A Aversa ◽  
S Basciani ◽  
P Visca ◽  
M Arizzi ◽  
L Gnessi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Oxygen Tension ◽  
Corpus Cavernosum ◽  
Platelet Derived Growth Factor ◽  
Pcr Analysis ◽  
Low Oxygen ◽  
Kidney Fibrosis ◽  
Low Oxygen Tension ◽  
Pdgfr Beta

Platelet-derived growth factor (PDGF) overactivity has been implicated in atherosclerosis and several fibrotic conditions including lung and kidney fibrosis, liver cirrhosis and myelofibrosis. Low oxygen tension (hypoxia) is a known stimulus for transcriptional induction of PDGF ligand and receptor genes in different tissues. We studied the expression and localization of PDGF-A, PDGF-B, and PDGF receptor (PDGFR)-alpha and -beta subunits in adult rat isolated corpus cavernosum (CC) under generalized transient hypoxia (pO(2) 10%) in comparison with normoxic conditions. Semi-quantitative RT-PCR analysis of mRNA extracted from rat penis showed higher amounts of PDGF-A, PDGF-B and PDGFR-beta mRNA transcripts in hypoxic versus normoxic animals. The immunohistochemical analysis showed that the localization of PDGF subunits and PDGFR-beta was confined to the cytoplasm of the perivascular smooth muscle cells, endothelium and trabecular fibroblasts. Our findings indicate that transient low oxygen tension induces PDGF overexpression in rat CC, which in the long term may lead to an increase of connective tissue production. We suggest that a local impairment of the PDGF/PDGFR system may contribute to CC fibrosis, which is an established cause of erectile dysfunction in man.

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