scholarly journals A Novel Insulin-Like Growth Factor (IGF)-Independent Role for IGF Binding Protein-3 in Mesenchymal Chondroprogenitor Cell Apoptosis

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 1695-1702 ◽  
Author(s):  
Lara Longobardi ◽  
Monica Torello ◽  
Caroline Buckway ◽  
Lynda O’Rear ◽  
William A. Horton ◽  
...  
Keyword(s):  
Binding Protein ◽  
Selective Reduction ◽  
Type Ii Collagen ◽  
Proteoglycan Synthesis ◽  
Chondrocyte Differentiation ◽  
Chondroprogenitor Cells ◽  
Apoptotic Effect ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

Chondrogenesis results from the condensation of mesenchymal chondroprogenitor cells (MCC) that proliferate and differentiate into chondrocytes. We have previously shown that IGF binding protein (IGFBP)-3 has an IGF-independent antiproliferative effect in MCC. The current study evaluates the IGF-independent apoptotic effect of IGFBP-3 on MCC to modulate chondrocyte differentiation. We employed the RCJ3.1C5.18 chondrogenic cell line, which in culture progresses from MCC to differentiated chondrocytes; cells do not express IGFs or IGFBP-3. We also used IGFBP-3 mutants with decreased (I56 substituted to G56; L80 and L81 to G80G81) or abolished binding for IGFs (I56, L80, and L81 to G56G80G81). MCC transfected with IGFBP-3 detached, changed their phenotype, and underwent apoptosis. A maximal IGFBP-3 apoptotic effect was observed 24 h after transfection (463 ± 73% of controls; P < 0.001). Remarkably, IGFBP-3 mutants had similar effects, demonstrating that the IGFBP-3 apoptotic action was clearly IGF independent. In addition, treatment with IGFBP-3 in serum-free conditions resulted in a significant increase of apoptosis (173 ± 23% of controls; P < 0.05). Moreover, this apoptotic effect was selective for MCC, resulting in a selective reduction of chondrocytic nodules and a significant decrease in type II collagen expression and proteoglycan synthesis. In summary, we have identified a novel IGF-independent role for IGFBP-3 in the modulation of chondrocyte differentiation.

Specimen processing time and measurement of total insulin-like growth factor-I (IGF-I), free IGF-I, and IGF binding protein-3 (IGFBP-3)

2006 ◽  
Vol 16 (2) ◽  
pp. 86-92 ◽  
Author(s):  
Tiffany G. Harris ◽  
Howard D. Strickler ◽  
Herbert Yu ◽  
Michael N. Pollak ◽  
E. Scott Monrad ◽  
...  
Keyword(s):  
Growth Factor ◽  
Processing Time ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Igf I ◽  
Specimen Processing ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

scholarly journals Genetic Determinants of Circulating Insulin-Like Growth Factor (IGF)-I, IGF Binding Protein (BP)-1, and IGFBP-3 Levels in a Multiethnic Population

2007 ◽  
Vol 92 (9) ◽  
pp. 3660-3666 ◽  
Author(s):  
Iona Cheng ◽  
Katherine DeLellis Henderson ◽  
Christopher A. Haiman ◽  
Laurence N. Kolonel ◽  
Brian E. Henderson ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Genetic Determinants ◽  
Igf I ◽  
Igf Binding ◽  
Multiethnic Population ◽  
Igf Binding Protein ◽  
Igfbp 3

scholarly journals Changes in Plasma Insulin-like Growth Factor (IGF)-1, IGF Binding Protein (IGFBP)-2 and IGFBP-3 during Fasting in Holstein Adult Steers and Calves

2000 ◽  
Vol 71 (2) ◽  
pp. 178-188
Author(s):  
Hong-Gu LEE ◽  
Renato Santa Ana VEGA ◽  
Long Thang PHUNG ◽  
Nobuyoshi MATSUNAGA ◽  
Hideto KUWAYAMA ◽  
...  
Keyword(s):  
Growth Factor ◽  
Plasma Insulin ◽  
Binding Protein ◽  
Insulin Like Growth Factor ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Igfbp 3

scholarly journals Interaction Between IGF Binding Protein-3 and TGFβ in the Regulation of Adipocyte Differentiation

Endocrinology ◽  
2012 ◽  
Vol 153 (10) ◽  
pp. 4799-4807 ◽  
Author(s):  
Hasanthi C. de Silva ◽  
Sue M. Firth ◽  
Stephen M. Twigg ◽  
Robert C. Baxter
Keyword(s):  
Binding Protein ◽  
Adipogenic Differentiation ◽  
Cell Types ◽  
Inhibitory Effect ◽  
Down Regulation ◽  
Smad2 Phosphorylation ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Interfering Rna ◽  
Igfbp 3

Abstract The development of white adipose tissue involves both the hypertrophy of existing adipocytes and the proliferation and differentiation of preadipocytes. Adipogenic differentiation is inhibited by TGFβ signaling through Smad2/3, and IGF binding protein-3 (IGFBP-3) is also known to activate Smad2/3 signaling in some cell types. We previously reported that exogenous or overexpressed IGFBP-3 inhibits adipogenesis in 3T3-L1 cells, but the role of endogenous IGFBP-3 in this process, and its possible interaction with TGFβ, is not known. During 10-d adipogenic differentiation initiated by insulin, dexamethasone, and 3-isobutyl-1-methylxanthine, 3T3-L1 cells expressed increasing levels of IGFBP-3 and TGFβ1, secreting over 1000 pg/ml of both proteins. Exogenous recombinant human IGFBP-3 paralleled TGFβ1 in stimulating Smad2 phosphorylation in 3T3-L1 preadipocytes, but no additive effect was observed for the two agents. In contrast, knockdown of endogenous IGFBP-3 by small interfering RNA (siRNA) significantly impaired Smad2 activation by 0.25 ng/ml TGFβ1. Transient expression of human IGFBP-3 significantly inhibited the induction of adipogenic markers adiponectin and resistin, and the appearance of lipid droplets, but down-regulation of endogenous IGFBP-3 by siRNA had little effect on the expression of either marker during the 10-d differentiation, compared with nonsilencing control siRNA. However, down-regulation of endogenous IGFBP-3 using two different siRNA significantly reversed the inhibitory effect of TGFβ1 on both adiponectin and resistin induction. We conclude that IGFBP-3 activates inhibitory Smad signaling in 3T3-L1 cells and that endogenous IGFBP-3 modulates their adipogenic differentiation by regulating cell sensitivity towards the inhibitory effect of TGFβ.

scholarly journals Perturbed Insulin-like Growth Factor-1 (IGF-1) and IGF Binding Protein-3 Are Not Associated with Chronic Widespread Pain in Men: Results from the European Male Ageing Study

2009 ◽  
Vol 36 (11) ◽  
pp. 2523-2530 ◽  
Author(s):  
JOHN McBETH ◽  
ABDELOUAHID TAJAR ◽  
TERENCE W. O’NEILL ◽  
GARY J. MACFARLANE ◽  
STEPHEN R. PYE ◽  
...  
Keyword(s):  
Growth Factor ◽  
Binding Protein ◽  
Chronic Widespread Pain ◽  
Insulin Like Growth Factor ◽  
Widespread Pain ◽  
Ageing Study ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Male Ageing ◽  
Igfbp 3

Objective.To determine whether perturbations of insulin-like growth factor-1 (IGF-1) and IGF binding protein-3 (IGFBP-3) were associated with the presence of chronic widespread pain (CWP) in men.Methods.The European Male Ageing Study (EMAS) is an 8-center population-based study of men aged 40–79 years recruited from population registers. A questionnaire asked about the presence and duration of musculoskeletal pain, from which subjects reporting CWP were identified. Subjects also had an interviewer-assisted questionnaire: levels of physical activity and mood were assessed, and height and weight were measured. IGF-1 and IGFBP-3 were assayed from a fasting blood sample. Logistic regression models were used to determine the association between IGF measures and CWP. Results were expressed as odds ratios or relative risk ratios.Results.A total of 3206 subjects provided full data. Of those, 1314 (39.0%) reported no pain in the past month and 278 (8.3%) reported pain that satisfied criteria for CWP. IGF-1 concentrations were similar among subjects who reported no pain and those with CWP: 131.5 mg/l and 128.4 mg/l, respectively. This was true also for IGFBP-3 (4.3 and 4.3 mg/l). Obesity was associated with low IGF-1 and a high IGFBP-3/IGF-1 ratio, indicating less bioavailable IGF-1, irrespective of pain status. This relationship persisted after adjustment for comorbidities, depression, smoking, alcohol consumption, and quality of life.Conclusion.Overall CWP was not associated with perturbations in IGF-1 and IGFBP-3 concentrations. Hypofunctioning of the axis was noted among subjects who were obese and this was not specific to CWP. These data suggest that IGF-1 is unlikely to be etiologically important in relation to CWP, although the relationship with growth hormone remains to be elucidated.

Moderate food restriction reduces serum IGF-I and alters circulating IGF-binding protein profiles in lactating rats

1997 ◽  
Vol 152 (2) ◽  
pp. 303-316 ◽  
Author(s):  
M H Monaco ◽  
S M Donovan
Keyword(s):  
Body Weight ◽  
Mammary Gland ◽  
Food Restriction ◽  
Binding Protein ◽  
Igf I ◽  
Pregnancy And Lactation ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Serum Gh ◽  
Igfbp 3

Abstract The role of somatogenic and lactogenic hormones in the adaptative mechanisms which occur in response to nutrient restriction during lactation is unknown. To characterize the effect of food restriction during lactation on serum IGF-I, GH and prolactin concentrations and serum IGF-binding protein (IGFBP) profiles, lactating dams had free access to food (control) or were restricted to 60% of control intake during pregnancy and lactation (RPL) or only during lactation (RL). Serum, milk and mammary gland samples were collected throughout lactation. RL dams lost body weight, control dams gained weight, while RPL dams maintained body weight during lactation. By day 20, body and mammary gland weights of RL and RPL dams did not differ and were lower than control (P<0·05). Serum IGF-I concentrations in restricted groups were lower than control (P<0·05), however, hepatic expression of IGF-I mRNA did not differ between groups in early (day 1) or mid-lactation (day 8) and was increased on day 20 in RL dams compared with RPL or control. These data suggest that serum IGF-I and hepatic IGF-I mRNA expression are not co-ordinately regulated in the food-restricted lactating rat. In early lactation, serum IGFBP-3 was lower in RPL dams than control (P<0·05), whereas IGFBP-1 and -2 were increased in RL and RPL dams in late lactation compared with control. The decrease in IGFBP-3 and increase in lower molecular weight IGFBP may have contributed to the reduction in serum IGF-I by increasing IGF-I clearance from the circulation. Serum GH and prolactin were measured in samples obtained between 0900 and 1200 h. Serum GH did not differ with the exception of an increase on day 1 in control relative to RPL dams and on day 20 in RL dams relative to RPL and control. Serum prolactin was higher in the RL dams than controls on day 4. In summary, food restriction during pregnancy and lactation or solely during lactation results in similar reductions in serum IGF-I and alterations in serum IGFBP despite differences in body weight responses to food restriction during lactation. Journal of Endocrinology (1997) 152, 303–316

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