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

Klaus, Günter; Weber, Lutz T.; Rodrı́guez, Julián; Fernández, Porfirio; Klein, Thomas; Grulich-Henn, Juergen; Hügel, Ulrike; Ritz, Eberhard; Mehls, Otto

doi:10.1046/j.1523-1755.1998.00884.x

Cited by 42 publications

(26 citation statements)

References 57 publications

(68 reference statements)

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“…Although there was an increase in BMP-7 and FGFR-3 staining during intermittent calcitriol therapy, there was no improvement in body length and tibial growth when administered in the presence of advanced secondary hyperparathyroidism. When given in higher doses, calcitriol attenuated the effects of IGF-I on DNA synthesis, colony formation, and cell proliferation in rat epiphyseal chondrocytes (17). It is interesting to note that PCNA staining correlated with tibial length measurements, IGF-I protein, and PTH/PTHrP receptor staining in the current study.…”

Section: Discussionsupporting

confidence: 52%

Daily or Intermittent Calcitriol Administration during Growth Hormone Therapy in Rats with Renal Failure and Advanced Secondary Hyperparathyroidism

Sanchez

He²

2005

Journal of the American Society of Nephrology

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Growth hormone (GH) improves growth in children with chronic renal failure. The response to GH may be affected by the degree of secondary hyperparathyroidism and concurrent treatment with vitamin D. Forty-six rats underwent 5/6 nephrectomy (Nx) and were given a high-phosphorus diet (Nx-Phos) to induce advanced secondary hyperparathyroidism and divided into the following groups: (1) Nx-Phos (n ‫؍‬ 10) received saline, (2) GH at 10 IU/kg per d (Nx-Phos؉GH; n ‫؍‬ 9), (3) GH and daily calcitriol (D) at 50 ng/kg per d (Nx-Phos؉GH؉daily D; n ‫؍‬ 8), (4) GH and intermittent D (three times weekly) at 350 ng/kg per wk (Nx-Phos؉GH؉int D; n ‫؍‬ 9), and (5) intact-control (n ‫؍‬ 10). Serum parathyroid hormone (PTH) levels were elevated in Nx-Phos, but IGF-I levels did not change with growth hormone. Body length, tibial length, and growth plate width did not increase with either GH or calcitriol. Proliferating cell nuclear antigen staining, PTH/PTHrP receptor, bone morphogenetic protein-7, and fibroblast growth factor receptor-3 expression increased with GH alone or with intermittent calcitriol but were slightly diminished during daily calcitriol administration. GH enhanced IGF-I, IGF binding receptor-3, and GH receptor but declined with daily and intermittent calcitriol. Overall, there was no improvement in body length, tibial length, and growth plate width at the end of GH therapy, but selected markers of chondrocyte proliferation and chondrocyte differentiation increased, although these changes were attenuated by calcitriol. The combination of GH and calcitriol that is frequently used in children with renal failure and secondary hyperparathyroidism require further studies to evaluate the optimal dose and frequency of administration to increase linear growth and prevent bone disease. G rowth hormone (GH) is a potent mitogenic agent that is frequently used to increase linear growth in children with chronic renal failure. The growth response, however, remains suboptimal in children who are maintained on chronic dialysis therapy compared with predialysis patients who are on conservative medical treatment (1). Causative factors that may contribute to the poor response to GH in dialysis children include a greater degree of GH insensitivity, increased severity of secondary hyperparathyroidism, differences in skeletal histology, concurrent treatment with vitamin D, and high doses of calcium salts.GH stimulates proliferation in various types of cells, including chondrocytes and osteoblasts, and increases collagen production either directly by binding to the GH receptor (GHR) or indirectly by increasing hepatic and local IGF-I production (2-4). Calcitriol (1,25-dihydroxyvitamin D 3 ) is used on a regular basis to maintain normocalcemia, control the development and progression of secondary hyperparathyroidism, and prevent renal bone disease in pediatric patients with chronic renal failure. Studies have shown that calcitriol exerts a dose-dependent antiproliferative effect on chondrocytes and osteoblasts (5). Mehls et al. (6) demon...

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Section: Discussionsupporting

confidence: 52%

Daily or Intermittent Calcitriol Administration during Growth Hormone Therapy in Rats with Renal Failure and Advanced Secondary Hyperparathyroidism

Sanchez

He²

2005

Journal of the American Society of Nephrology

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“…Thus, IGF-1 could exert effects partly through changes in vitamin D activation, whereas 1,25(OH) 2 D may act in part through changes in IGF-1 axis regulation. These findings provide the basis for interactions between these axes as reported experimentally in bony tissues (24,25) and in observational studies on breast density (18) and adiposity-related factors (16) …”

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confidence: 60%

25-Hydroxyvitamin D, IGF-1, and Metabolic Syndrome at 45 Years of Age

Hyppönen¹,

et al. 2008

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OBJECTIVE-Hypovitaminosis D and reduced IGF-1 are associated, individually, with metabolic syndrome. Physiological interactions between vitamin D and IGF-1 are reported; this is the first study to investigate their combined associations with metabolic syndrome prevalence. RESEARCH DESIGN AND METHODS-Data on 25-hydroxyvitamin D (25(OH)D), IGF-1, and metabolic syndrome abnormalities (abdominal obesity; raised A1C, blood pressure, and triglycerides; and low HDL cholesterol) were collected from 6,810 British white subjects in the 1958 cohort, surveyed during 2002-2004 (age 45 years). RESULTS-IGF-1 concentrations increased with 25(OH)D up toϳ75-85 nmol/l but not thereafter. Both 25(OH)D and IGF-1 were inversely associated with metabolic syndrome. There was an interaction between 25(OH)D and IGF-1 (P ϭ 0.025) on metabolic syndrome prevalence: IGF-1 was not significantly associated with metabolic syndrome among those with the lowest levels of 25(OH)D (P Ͼ 0.09), whereas higher 25(OH)D was associated with metabolic syndrome at all IGF-1 concentrations (P Յ 0.006). Metabolic syndrome prevalence was lowest for participants with the highest concentrations of both 25(OH)D and IGF-1 (odds ratio for highest vs. lowest third of both 0.26 [95% CI 0.17-0.40], P Ͻ 0.0001; adjusted for sex, month, hour, inactivity, alcohol consumption, smoking, and social class). 25(OH)D was associated with the prevalence of high A1C, blood pressure, and triglycerides after adjustment for IGF-1, obesity, and social and lifestyle variations (P Յ 0.004 for all comparisons). (1,2); however, for both factors, lower concentrations have been associated with disturbed glucose metabolism (3-8), high blood pressure (9 -11), adverse lipid profiles (2,12,13), and cardiovascular disease (8,14,15) independently of body mass. The evidence for associations between vitamin D and IGF-1 axes with metabolic risk includes prospective studies, clinical trials, and dose-related effects, suggesting that associations may prove to be causal. Mechanisms by which vitamin D and IGF-1 axes may lead to human disease are, however, not fully understood, and despite evidence for physiological interaction between these risk factors (16 -18), little is known about their joint effects, and we can find no previous studies investigating their combined associations with metabolic syndrome. CONCLUSIONS-SerumVitamin D is a hormone precursor, which before exerting its metabolic effects undergoes two successive hydroxylations.

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“…Previously, both proliferative and antiproliferative effects have been induced with this vitamin in chondrocytes from the resting and upper proliferative zones of growth plate [Takano-Yamamoto et al, 1992;Klaus et al, 1998]. In this study, 1·,25-dihydroxyvitamin D 3 did not significantly modify [ 3 H]-thymidine incorporation in the absence of growth factors, but tended to decrease it when 210 Cells Tissues Organs 2004;177:201-211 Panasyuk/Khatib/Colantuoni/Quintero/ Lomri/Mitrovic these were present in the culture medium.…”

Section: Fig 6 Autoradiograph Of Rt-pcr Gelmentioning

confidence: 99%

Method for Selecting Populations of Rat Articular Chondrocytes That Exhibit Distinct Growth and Metabolic Characteristics, and Their Responses to Growth Factors, PMA and Vitamin D<sub>3</sub>

Panasyuk

Khatib

Colantuoni

et al. 2004

Cells Tissues Organs

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Chondrocytes were released from articular cartilage fragments of 6-week-old Wistar rats by a 2-hour treatment with bacterial collagenase. The cells from one animal were seeded in a 25-cm² culture flask at a density of 10⁵ cells/cm². After 1 h, the flask was gently shaken and the medium, containing nonadherent cells, was transferred to a new flask. The attached cells were incubated with 5 ml of fresh medium. This procedure was repeated after 3, 24, 48 and 96 h. Resulting cell populations were then analyzed. The earlier cells attached, the more rapidly they proliferated, and the less collagen and proteoglycan (PG) they produced. The cells that attached after 24 h grew much more slowly, piled up in many areas, exhibited strong alkaline phosphatase activity and calcified extracellular matrix (ECM). Differences in deoxyribonucleic acid (DNA) and protein/PG synthesis were also observed when these cell populations were challenged with growth factors and 12-myristate 13-acetate (PMA). Pretreatment of cells for 2 h with PMA strongly enhanced DNA and PG synthesis only in cultures containing insulin-like growth factor-1. Nonselected rat articular chondrocytes (AC) subcultured at least four times as monolayers still expressed mRNA specific for aggrecan and type II collagen, suggesting conservation of the chondrogenic phenotype. In conclusion, AC of young individuals seem to be heterogeneous with respect to their capacity to proliferate and synthesize ECM. By selecting and expanding in vitro the appropriate cell population, this method could be potentially useful for studies aimed at repairing damaged cartilage.

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

Cited by 42 publications

References 57 publications

Daily or Intermittent Calcitriol Administration during Growth Hormone Therapy in Rats with Renal Failure and Advanced Secondary Hyperparathyroidism

Daily or Intermittent Calcitriol Administration during Growth Hormone Therapy in Rats with Renal Failure and Advanced Secondary Hyperparathyroidism

25-Hydroxyvitamin D, IGF-1, and Metabolic Syndrome at 45 Years of Age

Method for Selecting Populations of Rat Articular Chondrocytes That Exhibit Distinct Growth and Metabolic Characteristics, and Their Responses to Growth Factors, PMA and Vitamin D<sub>3</sub>

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