Studies on regulation of insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-4 production in human bone cells

1992 ◽  
Vol 127 (6) ◽  
pp. 555-564 ◽  
Author(s):  
Subburaman Mohan ◽  
Donna D Strong ◽  
Uta G Lempert ◽  
Florence Tremollieres ◽  
Jon E Wergedal ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Conditioned Medium ◽  
Cell Cultures ◽  
Bone Cells ◽  
Human Growth ◽  
Bone Cell ◽  
Human Bone ◽  
Human Bone Cell ◽  
Igf I ◽  
Igfbp 3

Previous studies have shown that the actions of IGF-II in bone are determined not only by its concentration, but also by the concentration of IGFBP-4 as well as other IGFBPs. In this study, we sought to determine by Western ligand blotting the effects of growth hormone, IGF-I and IGF-II on the production of IGFBP-3 and IGFBP-4 in TE89 human osteosarcoma cells and in untransformed normal human bone cells derived from rib. Human growth hormone at 10 μg/l decreased the amount of IGFBP-4 but had no effect on the IGFBP-3 level in the conditioned medium of low density cultures of TE89 cells and human bone cells derived from rib. Human growth hormone had no effect on IGFBP-3 or IGFBP-4 levels in the conditioned medium of high density human bone cell cultures. IGF-I and IGF-II, which increased human bone cell proliferation, decreased the level of IGFBP-4 (30% of control at 100 μg/l IGF-I and IGF-II) but increased the level of IGFBP-3 (3–10 fold at 100 μg/l IGF-I and IGF-II) after 48 h of treatment in the conditioned medium of both low and high density TE89 cell cultures. Similar changes in IGFBP-3 and IGFBP-4 levels were also seen in the conditioned medium of human bone cells derived from rib after treatment with IGF-I and IGF-II. Studies to determine the underlying molecular mechanisms by which IGF-II decreased the amount of IGFBP-4 in the conditioned medium revealed that IGF-II decreased the IGFBP-4 mRNA abundance and increased the IGFBP-3 mRNA abundance in human bone cells. Based on the above findings, we conclude that the production of both IGFBP-3 and IGFBP-4 is regulated in bone cells and that local and systemic agents may modulate the responsiveness of bone cells to IGFs by regulated secretion of IGFBP-3 and IGFBP-4.

Hemoglobin level is linked to growth hormone-dependent proteins in short children

Blood ◽  
1996 ◽  
Vol 87 (5) ◽  
pp. 2075-2081 ◽  
Author(s):  
E Vihervuori ◽  
M Virtanen ◽  
H Koistinen ◽  
R Koistinen ◽  
M Seppala ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Skeletal Dysplasia ◽  
Recombinant Human Growth Hormone ◽  
Body Height ◽  
Human Growth ◽  
Gh Treatment ◽  
Blood Hemoglobin ◽  
Igf I ◽  
Igfbp 3

Erythropoiesis was investigated in 32 children wih short stature and in eight children with skeletal dysplasia by studying blood hemoglobin in relation to growth and to serum concentrations of insulin-like growth factor I (IGF-I), IGF binding protein-3 (IGFBP-3), and erythropoietin (EPO) before, during, and after 12 months of recombinant human growth hormone (GH) treatment. Blood hemoglobin concentration was positively correlated with relative body height and with serum IGF-I and IGFBP-3 levels (P = .001 to .02), but not with the concentrations of EPO. The normal age-dependency of hemoglobin was lacking. Hemoglobin levels and their responses to GH treatment were similar in the patients with GH deficiency and those with normal GH secretion. Treatment with GH accelerated growth and elevated the concentrations of hemoglobin, IGF- I, and IGFBP-3. In the eight patients with skeletal dysplasia, body mass increased similarly, but gain in height was less than in the other patients, and the increase in hemoglobin was markedly pronounced. In this group, the correlations between hemoglobin, IGF-I, and IGFBP-3 were extremely close (r = 0.80 to 0.85, P = .031 to .008). These findings are in accord with earlier observations from in vitro and animal studies, and suggest that the GH-IGF axis is involved in the physiologic elevation of hemoglobin levels during childhood.

Progesterone and promegestone stimulate human bone cell proliferation and insulin-like growth factor-2 production

1992 ◽  
Vol 126 (4) ◽  
pp. 329-337 ◽  
Author(s):  
Florence A Tremollieres ◽  
Donna D Strong ◽  
David J Baylink ◽  
Subburaman Mohan
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Bone Formation ◽  
Conditioned Medium ◽  
Bone Cell ◽  
Human Bone ◽  
Osteoblastic Cells ◽  
Human Bone Cell ◽  
Bone Cell Proliferation ◽  
Human Osteoblastic Cells

Recent clinical studies suggest that progesterone may be involved in the regulation of bone turnover and could promote bone formation. This study was undertaken to evaluate whether progesterone and promegestone (a 19 nor-PG derivative) may have a direct effect on human bone cells and, if so, whether growth factor production could be involved in promoting this effect. The osteosarcoma cell line TE85 and untransformed normal human osteoblastic cells derived from iliac crest were used as in vitro model systems. Progesterone and promegestone were found to significantly increase [3H]thymidine incorporation in TE8 5 cells in a dose-dependent manner at concentrations ranging from 10−12to 10−8 mol/l after four days of cultivation (p<0.01, ANOVA). Consistent with this response in the TE85 cells, progesterone and promegestone increased cell number in human osteoblastic cells after six days of treatment (p<0.05. ANOVA). To determine whether this effect on cell proliferation was mediated by the insulin-like growth factor (IGF) regulatory system, the levels of IGF-1, IGF-2 and IGF binding protein (IGFBP) were measured in the conditioned media of both TE85 and human osteoblast cells. While no significant changes in IGF-1 levels were found in the conditioned media of progesterone and promegestone treated cultures, progesterone and promegestone at the concentration of 5 nmol/l significantly increased IGF-2 levels 2.4 and 1.5-fold respectively, at 48 h in the conditioned medium of TE8 5 cells as compared to control. Similarly, a 4.1 and 1.9-fold increase in IGF-2 levels was found upon treatment with progesterone and promegestone in human osteoblastic cells. Consistent with the increased secretion of IGF-2 into the conditioned medium, IGF-2 mRNA levels were found to be increased in TE85 cells. A 4.9 kb transcript was increased 2.7 and 3.7-fold respectively after 6 h of exposure to 5 nmol/l of progesterone and promegestone as compared to control. Western ligand blot analysis of conditioned medium collected from TE85 and human osteoblast cell cultures treated with progesterone and promegestone revealed no changes in the levels of IGFBP-3 and IGFBP-4 after 48 h of treatment. Consistent with these results, the IGFBP-4 mRNA level was unaffected. These data suggest that both progesterone and promegestone stimulate human bone cell proliferation and that the mechanism may in part involve increased IGF-2 secretion. Because IGF-2 has been proposed to play a potential role in the coupling of bone formation to bone resorption, it follows that progesterone deficiency may be involved in the uncoupling that occurs in postmenopause. In any case, the findings that progesterone and promegestone have direct effects on bone formation could have physiological implications.

Response of normal and osteoporotic human bone cells to mechanical stress in vitro

1998 ◽  
Vol 274 (6) ◽  
pp. E1113-E1120 ◽  
Author(s):  
Jozien G. H. Sterck ◽  
Jenneke Klein-Nulend ◽  
Paul Lips ◽  
Elisabeth H. Burger
Keyword(s):  
Nitric Oxide ◽  
Mechanical Stress ◽  
Cell Cultures ◽  
Bone Cells ◽  
Bone Cell ◽  
Human Bone ◽  
Animal Bone ◽  
Bone Cell Cultures

Bone adapts to mechanical stress, and bone cell cultures from animal origin have been shown to be highly sensitive to mechanical stress in vitro. In this study, we tested whether bone cell cultures from human bone biopsies respond to stress in a similar manner as animal bone cells and whether bone cells from osteoporotic patients respond similarly to nonosteoporotic donors. Bone cell cultures were obtained as outgrowth from collagenase-stripped trabecular bone fragments from 17 nonosteoporotic donors between 7 and 77 yr of age and from 6 osteoporotic donors between 42 and 72 yr of age. After passage, the cells were mechanically stressed by treatment with pulsating fluid flow (PFF; 0.7 ± 0.03 Pa at 5 Hz for 1 h) to mimic the stress-driven flow of interstitial fluid through the bone canaliculi, which is likely the stimulus for mechanosensation in bone in vivo. Similar to earlier studies in rodent and chicken bone cells, the bone cells from nonosteoporotic donors responded to PFF with enhanced release of prostaglandin E2(PGE2) and nitric oxide as well as a reduced release of transforming growth factor-β (TGF-β). The upregulation of PGE2 but not the other responses continued for 24 h after 1 h of PFF treatment. The bone cells from osteoporotic donors responded in a similar manner as the nonosteoporotic donors except for the long-term PGE2 release. The PFF-mediated upregulation of PGE2 release during 24 h of postincubation after 1 h of PFF was significantly reduced in osteoporotic patients compared with six age-matched controls as well as with the whole nonosteoporotic group. These results indicate that enhanced release of PGE2 and nitric oxide, as well as reduced release of TGF-β, is a characteristic response of human bone cells to fluid shear stress, similar to animal bone cells. The results also suggest that bone cells from osteoporotic patients may be impaired in their long-term response to mechanical stress.

Lithium stimulates cell proliferation in human bone cell cultures

Bone ◽  
1995 ◽  
Vol 17 (6) ◽  
pp. 572 ◽  
Author(s):  
Klaus Seuwen ◽  
Rudolf Wälchli
Keyword(s):  
Cell Proliferation ◽  
Cell Cultures ◽  
Bone Cell ◽  
Human Bone ◽  
Human Bone Cell ◽  
Bone Cell Cultures

scholarly journals Enhancement of the peripheral sensitivity to growth hormone in adults with GH deficiency

2001 ◽  
pp. 267-272 ◽  
Author(s):  
G Aimaretti ◽  
G Fanciulli ◽  
S Bellone ◽  
M Maccario ◽  
E Arvat ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Day Treatment ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Normal Subjects ◽  
Short Treatment ◽  
Igf I ◽  
Composition Structure ◽  
Igfbp 3

OBJECTIVE: Adults with severe GH deficiency (GHD) need recombinant human growth hormone (rhGH) replacement to restore body composition, structure functions and metabolic abnormalities. The optimal rhGH dose for replacement has been progressively reduced to avoid side effects. The aim of the present study was to define the minimal rhGH dose able to increase both IGF-I and IGF binding protein (BP)-3 levels in GHD and to verify the possible change in GH sensitivity. DESIGN AND PATIENTS: To this goal, we studied the effect of 4-day treatment with 3 rhGH doses (1.25, 2.5 and 5.0 microg/kg/day) on IGF-I and IGFBP-3 levels in 25 panhypopituitary adults with severe GHD (12 males and 13 females, age: 44.5+/-3.0 years, body mass index (BMI): 27.0+/-0.9 kg/m(2)) and 21 normal young adult volunteers (NV, 12 males and 9 females, age: 30.5+/-2.0 years, BMI: 20.8+/-0.5 kg/m(2)). RESULTS: Basal IGF-I and IGFBP-3 levels in GHD were lower (P<0.001) than in NV. In NV the 1.25 microg/kg dose of rhGH did not modify IGF-I levels. The dose of 2.5 microg/kg rhGH significantly increased IGF-I levels in men (P<0.001) but not in women, while the 5.0 microg/kg dose increased IGF-I levels in both sexes (P<0.001). IGFBP-3 levels were not modified by any of the administered rhGH doses. In GHD patients, all rhGH doses increased IGF-I levels 12 h after both the first (P<0.01) and the fourth rhGH dose (P<0.001). At the end of treatment percentage increases in IGF-I were higher (P<0.001) in GHD patients than in NV. In contrast with NV, in GHD patients the IGF-I response to short-term stimulation with rhGH was independent of gender. Moreover, GHD patients showed increases in IGFBP-3 after the fourth administration of both 2.5 and 5.0 microg/kg rhGH. CONCLUSION: The results of the present study demonstrate that the minimal rhGH dose able to increase IGF-I and IGFBP-3 levels in GHD patients is lower than in normal subjects, at least after a very short treatment. This evidence suggests an enhanced peripheral GH sensitivity in GH deprivation.

Basal characteristics and first year responses to human growth hormone (GH) vary according to diagnostic criteria in children with non-acquired GH deficiency (naGHD): observations from a single center over a period of five decades

2018 ◽  
Vol 0 (0) ◽  
Author(s):  
Michael B. Ranke ◽  
Roland Schweizer ◽  
Gerhard Binder
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Diagnostic Criteria ◽  
Human Growth Hormone ◽  
Human Growth ◽  
Height Velocity ◽  
First Year ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Igfbp 3

Abstract Background Children with non-acquired (na) growth hormone deficiency (GHD) diagnosed over decades in one center may provide perspective insight. Methods naGHD is divided into idiopathic GHD (IGHD), GHD of known cause (cGHD) and GHD neurosecretory dysfunction (NSD); time periods: <1988 (I); 1988–1997 (II); 1998–2007 (III); 2008–2015 (IV). Descriptive analyses were performed at diagnosis and during first year GH treatment. Results Patients (periods, N): I, 87; II, 141; III, 356; IV, 51. In cGHD (all), age, maximum GH, insulin-like growth factor-I (IGF-I), and insulin-like growth factor-binding protein-3 (IGFBP-3) (5.1 years, 3.6 μg/L, −5.3 standard deviation score [SDS], −3.7 SDS) were lower than in IGHD (all) (6.8 years 5.8 μg/L, −2.5 SDS, −1.0 SDS), but not height (−3.1 vs. −3.2 SDS). Characteristics of NSD were similar to that of IGHD. Patients with IGHD – not cGHD – diagnosed during 2008–2015 (IV) were the youngest with most severe GHD (maxGH, IGF-I, IGFBP-3), and first year height velocity (HV) and ∆ IGF-I (10.5 cm/year, 4.0 SDS) but not ∆ height SDS were the highest on recombinant human growth hormone (rhGH) (27 μg/kg/day). Conclusions Although during 1988–2007 patient characteristics were similar, the recently (>2008) stipulated more stringent diagnostic criteria – HV before testing, sex steroid priming, lower GH cut-off – have restricted diagnoses to more severe cases as they were observed before the rhGH era.

Sign in / Sign up

Export Citation Format

Share Document