scholarly journals Interaction of IGF-I and 1α,25(OH)2D3 on receptor expression and growth stimulation in rat growth plate chondrocytes

1998 ◽  
Vol 53 (5) ◽  
pp. 1152-1161 ◽  
Author(s):  
Günter Klaus ◽  
Lutz Weber ◽  
Julian Rodríguez ◽  
Porfirio Fernández ◽  
Thomas Klein ◽  
...  
Keyword(s):  
Growth Plate ◽  
Growth Stimulation ◽  
Receptor Expression ◽  
Growth Plate Chondrocytes ◽  
Igf I ◽  
Rat Growth

scholarly journals Defined Carboxy-Terminal Fragments of Insulin-Like Growth Factor (IGF) Binding Protein-2 Exert Similar Mitogenic Activity on Cultured Rat Growth Plate Chondrocytes as IGF-I

Endocrinology ◽  
2008 ◽  
Vol 149 (10) ◽  
pp. 4901-4911 ◽  
Author(s):  
Daniela Kiepe ◽  
Anke Van Der Pas ◽  
Sonia Ciarmatori ◽  
Ludger Ständker ◽  
Burkhardt Schütt ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Biological Activity ◽  
Growth Plate ◽  
Longitudinal Growth ◽  
Growth Plate Chondrocytes ◽  
Igf I ◽  
Rat Growth ◽  
Igf Binding ◽  
Carboxy Terminal ◽  
Igf Binding Protein

The IGF/IGF binding protein (IGFBP) system is an important component in the hormonal regulation of longitudinal growth. Evidence from in vitro studies indicates that IGFBPs may have IGF-independent effects. We analyzed the biological activity of intact IGFBP-2 and defined carboxy-terminal IGFBP-2 fragments isolated from human hemofiltrate in two cell culture systems of the growth plate: rat growth plate chondrocytes in primary culture and the mesenchymal chondrogenic cell line RCJ3.1C5.18. The IGFBP-2 fragments IGFBP-2167–279, IGFBP-2167–289, and IGFBP-2104–289 exerted a strong (2- to 3-fold) mitogenic effect on growth plate chondrocytes, which was comparable with IGF-I in equimolar concentrations (7.8 nm) but was not mediated through the type 1 IGF receptor. In a dose-response experiment, the most effective concentration of IGFBP-2104–289 for the stimulation of cell proliferation was 10 nm. This biological activity of IGFBP-2 fragments was associated with cell membrane binding, demonstrated by Western blot analysis of fractionated cell lysates and immunohistochemistry. Whereas intact IGFBP-2 did not modulate chondrocyte proliferation, partially reduced (by dithiothreitol) full-length IGFBP-2 stimulated cell proliferation to a comparable extent (3.4-fold) as carboxy-terminal IGFBP-2 fragments. The mitogenic activity of these IGFBP-2 fragments and of partially reduced full-length IGFBP-2 was mediated through the use of the MAPK/ERK 1/2. These data imply a novel role of naturally occurring IGFBP-2 fragments for the endocrine and paracrine/autocrine regulation of longitudinal growth.

scholarly journals Insulin-Like Growth Factor (IGF)-I Stimulates Cell Proliferation and Induces IGF Binding Protein (IGFBP)-3 and IGFBP-5 Gene Expression in Cultured Growth Plate Chondrocytes via Distinct Signaling Pathways

Endocrinology ◽  
2005 ◽  
Vol 146 (7) ◽  
pp. 3096-3104 ◽  
Author(s):  
Daniela Kiepe ◽  
Sonia Ciarmatori ◽  
Andreas Hoeflich ◽  
Eckhard Wolf ◽  
Burkhard Tönshoff
Keyword(s):  
Signaling Pathways ◽  
Growth Plate ◽  
Intracellular Signaling ◽  
De Novo ◽  
Growth Plate Chondrocytes ◽  
Intracellular Signaling Pathways ◽  
Igf I ◽  
Rat Growth ◽  
Igf Binding ◽  
Igfbp 3

Abstract The bioactivity of IGF-I in the cellular microenvironment is modulated by both inhibitory and stimulatory IGF binding proteins (IGFBPs), whose production is partially under control of IGF-I. However, little is known on the IGF-mediated regulation of these IGFBPs in the growth plate. We therefore studied the effect of IGF-I on IGFBP synthesis and the involved intracellular signaling pathways in two cell culture models of rat growth plate chondrocytes. In growth plate chondrocytes in primary culture, incubation with IGF-I increased the concentrations of IGFBP-3 and IGFBP-5 in conditioned cell culture medium in a dose- and time-dependent manner. Coincubation of IGF-I with specific inhibitors of the p42/44 MAPK pathway (PD098059 or U0126) completely abolished the stimulatory effect of IGF-I on IGFBP-3 mRNA expression but did not affect increased IGFBP-5 mRNA levels. In contrast, inhibition of the phosphatidylinositol-3 kinase signaling pathway by LY294002 abrogated both IGF-I-stimulated IGFBP-3 and -5 mRNA expression. Comparable results regarding IGFBP-5 were obtained in the mesenchymal chondrogenic cell line RCJ3.1C5.18, which does not express IGFBP-3. The IGF-I-induced IGFBP-5 gene expression required de novo mRNA transcription and de novo protein synthesis. These data suggest that IGF-I modulates its activity in cultured rat growth plate chondrocytes by the synthesis of both inhibitory (IGFBP-3) and stimulatory (IGFBP-5) binding proteins. The finding that IGF-I uses different and only partially overlapping intracellular signaling pathways for the regulation of two IGFBPs with opposing biological functions might be important for the modulation of IGF bioactivity in the cellular microenvironment.

scholarly journals Valproic Acid Impacts the Growth of Growth Plate Chondrocytes

2020 ◽  
Vol 17 (10) ◽  
pp. 3675
Author(s):  
Hueng-Chuen Fan ◽  
Shih-Yu Wang ◽  
Yi-Jen Peng ◽  
Herng-Sheng Lee
Keyword(s):  
Valproic Acid ◽  
Short Stature ◽  
Growth Plate ◽  
Caspase 3 ◽  
Skeletal Growth ◽  
Growth Plate Chondrocytes ◽  
Protein Levels ◽  
Rat Growth ◽  
Cox 2 ◽  
Bone Abnormalities

A range of bone abnormalities including short stature have been reported to be associated with the use of antiepileptic drugs (AEDs) in children. Exactly how AEDs impact skeletal growth, however, is not clear. In the present study, rat growth plate chondrocytes were cultured to study the effects of AEDs, including valproic acid (VPA), oxcarbazepine (OXA), levetiracetam (LEV), lamotrigine (LTG), and topiramate (TPM) on the skeletal growth. VPA markedly reduced the number of chondrocytes by apoptosiswhile other AEDs had no effect. The apoptosis associated noncleaved and cleaved caspase 3, and caspases were increased by exposure to VPA, which up-regulated cyclooxygenase 2 (COX-2) mRNA and protein levels likely through histone acetylation. The COX-2 inhibitor NS-398 attenuated the effects of VPA up-regulating COX-2 expression and decreased VPA-induced caspase 3 expression. The use of VPA in children should be closely monitored or replaced, where appropriate, by AEDs which do not apparently affect the growth plate chondrocytes.

Autoradiographic Evidence of Opioid Binding Sites in Rat Growth Plate Chondrocytes

1992 ◽  
Vol 55 (3) ◽  
pp. 357-359 ◽  
Author(s):  
Manuel Freire-Garabal ◽  
Maria Teresa Castaño ◽  
Angel Belmonte ◽  
Javier Jorge ◽  
José Couceiro ◽  
...  
Keyword(s):  
Growth Plate ◽  
Binding Sites ◽  
Growth Plate Chondrocytes ◽  
Opioid Binding ◽  
Rat Growth

Rat growth plate chondrocytes express low levels of 25-hydroxy-1α-hydroxylase

2004 ◽  
Vol 89-90 ◽  
pp. 143-147 ◽  
Author(s):  
Ulrike Hügel ◽  
Lutz Weber ◽  
Jörg Reichrath ◽  
Otto Mehls ◽  
Günter Klaus
Keyword(s):  
Growth Plate ◽  
Growth Plate Chondrocytes ◽  
Rat Growth ◽  
Low Levels

Pi transport regulation by chicken growth plate chondrocytes

1994 ◽  
Vol 267 (1) ◽  
pp. E24-E31
Author(s):  
C. Montessuit ◽  
J. P. Bonjour ◽  
J. Caverzasio
Keyword(s):  
Growth Plate ◽  
Primary Cultures ◽  
Growth Plate Chondrocytes ◽  
Phosphonoformic Acid ◽  
Pi Transport ◽  
Igf I ◽  
Sodium Dependent ◽  
Half Maximal Effective Concentration ◽  
Cartilage Cells ◽  
Extracellular Sodium

Inorganic phosphate (Pi) is a key element for the growth and mineralization of the epiphyseal cartilage. In this study, the characteristics of the transport of Pi in growth plate chondrocytes have been determined using primary cultures of chicken growth plate cartilage cells. The uptake of Pi was significantly increased in the presence of extracellular sodium. The kinetic parameters of the saturable sodium-dependent Pi transport (NaPiT) were determined. The Michaelis constant for Pi was 0.443 +/- 0.095 mM, and the concentration of sodium with which half-maximal Pi transport was observed was 48.0 +/- 8.7 mM. Stoichiometric analysis suggested that more than one sodium ion was cotransported with each Pi molecule. NaPiT was sensitive to inhibition by Pi analogues such as phosphonoformic acid and arsenate. These data strongly suggest that Pi uptake by chicken growth plate chondrocytes is a carrier-mediated process driven by the transmembrane electrochemical gradient of sodium. Two important regulators of biosynthetic activities of growth plate chondrocytes, insulin-like growth factor I (IGF-I) and parathyroid hormone (PTH), selectively regulated Pi transport. With IGF-I, maximal stimulation (117 +/- 7% above control) was observed at doses > 5 nM, with an half-maximal effective concentration of 0.46 +/- 0.18 nM. A significant effect was observed after 1 h of exposure and was maintained for up to 24 h. PTH increased Pi transport with a biphasic dose-response curve. The change in NaPiT was transient, being maximally observed after 8 h (58 +/- 8%) and unexpressed after 24 h.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Inhibition of IGF-I–related intracellular signaling pathways by proinflammatory cytokines in growth plate chondrocytes

2014 ◽  
Vol 76 (3) ◽  
pp. 245-251 ◽  
Author(s):  
Daniela Choukair ◽  
Ulrike Hügel ◽  
Anja Sander ◽  
Lorenz Uhlmann ◽  
Burkhard Tönshoff
Keyword(s):  
Signaling Pathways ◽  
Growth Plate ◽  
Proinflammatory Cytokines ◽  
Intracellular Signaling ◽  
Growth Plate Chondrocytes ◽  
Intracellular Signaling Pathways ◽  
Igf I

scholarly journals Imaging IGF-I uptake in growth plate cartilage using in vivo multiphoton microscopy

2017 ◽  
Vol 123 (5) ◽  
pp. 1101-1109 ◽  
Author(s):  
Maria A. Serrat ◽  
Gabriela Ion
Keyword(s):  
Real Time ◽  
Growth Plate ◽  
Multiphoton Microscopy ◽  
Biologically Active ◽  
Growth Plate Chondrocytes ◽  
Growth Plates ◽  
Metatarsal Bones ◽  
Wide Range ◽  
Igf I

Bones elongate through endochondral ossification in cartilaginous growth plates located at ends of primary long bones. Linear growth ensues from a cascade of biochemical signals initiated by actions of systemic and local regulators on growth plate chondrocytes. Although cellular processes are well defined, there is a fundamental gap in understanding how growth regulators are physically transported from surrounding blood vessels into and through dense, avascular cartilage matrix. Intravital imaging using in vivo multiphoton microscopy is one promising strategy to overcome this barrier by quantitatively tracking molecular delivery to cartilage from the vasculature in real time. We previously used in vivo multiphoton imaging to show that hindlimb heating increases vascular access of large molecules to growth plates using 10-, 40-, and 70-kDa dextran tracers. To comparatively evaluate transport of similarly sized physiological regulators, we developed and validated methods for measuring uptake of biologically active IGF-I into proximal tibial growth plates of live 5-wk-old mice. We demonstrate that fluorescently labeled IGF-I (8.2 kDa) is readily taken up in the growth plate and localizes to chondrocytes. Bioactivity tests performed on cultured metatarsal bones confirmed that the labeled protein is functional, assessed by phosphorylation of its signaling kinase, Akt. This methodology, which can be broadly applied to many different proteins and tissues, is relevant for understanding factors that affect delivery of biologically relevant molecules to the skeleton in real time. Results may lead to the development of drug-targeting strategies to treat a wide range of bone and cartilage pathologies. NEW & NOTEWORTHY This paper describes and validates a novel method for imaging transport of biologically active, fluorescently labeled IGF-I into skeletal growth plates of live mice using multiphoton microscopy. Cellular patterns of fluorescence in the growth plate were completely distinct from our prior publications using biologically inert probes, demonstrating for the first time in vivo localization of IGF-I in chondrocytes and perichondrium. These results form important groundwork for future studies aimed at targeting therapeutics into growth plates.

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