The relationships of alkaline phosphatase and bone alkaline phosphatase to the growth hormone/insulin-like growth factor-1 axis and vitamin D status in children with growth hormone deficiency

Witkowska–Sędek, Ewelina; Stelmaszczyk-Emmel, Anna; Majcher, Anna; Demkow, Urszula; Pyrżak, Beata

doi:10.18388/abp.2017_2541

Cited by 9 publications

(7 citation statements)

References 41 publications

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“…ALP, as a marker of early osteoblast differentiation, began to appear in the extracellular matrix synthesis phase and reached its peak in the mineralized nodule formation phase [24]. In this study, MC3T3-E1 cells cultured in the 10 and 20 ng/ml of icariin exhibited the significantly increase in ALP activity (P < 0.01).…”

Section: Discussionsupporting

confidence: 48%

Icariin induces MC3T3-E1 cell proliferation and differentiation via the BMP-2/Smads/Runx2 signal pathway

Gou

et al. 2018

Preprint

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Icariin, the main active ingredient of Epimedium, has played an important role in bone anabolism. However, the molecular mechanism for this effect was not convincingly reported yet. In this paper, the role of icariin on cell morphology, viability, cell cycling and the activity of alkaline phosphatase (ALP) were studied, and the molecular mechanism of icariin induced osteogenic effect was also investigated. Icariin with different concentrations (10, 20 and 40 ng/ml) was used to modify the pre-osteoblastic MC3T3-E1 cells for 48, 72 and 96 h, and the proliferation, morphology, and the cell cycle of the cells were evaluated by Cell Counting Kit-8 (CCK-8), microscopy and flow cytometry, respectively. Bone morphogenic protein-2 (BMP-2), bone morphogenic protein receptor-2 (BMPR-2), Smad4, Smadl/5/8 proteins expression levels were obtained by Western blotting and the expression levels of runt-related transcription factor 2 (Runx2) mRNA was examined by reverse transcription-polymerase chain reaction (RT-PCR). In this study, we found that icariin could promote the proliferation and differentiation of MC3T3-E1 cells in a dose-and time-dependent manner. Icariin could stimulate the expression of the BMP-2, BMPR-2, Smad4 and Smadl/5/8 proteins.Furthermore, icariin could upregulate the expression of Runx2 mRNA. These results showed that icariin played an important role in upregulating BMP-2 expression to activate the BMP-2/Smads/Runx2 signal pathway for increasing both the proliferation and differentiation of the MC3T3-E1 cells. However, the osteogenic effects of icariin can be suppressed by the BMP-2 antagonist (Noggin). In conclusion, we demonstrate that icariin is an osteoinductive factor that exerts its osteogenic effect by regulating the BMP-2/Smads/Runx2 signal pathway in MC3T3-E1 cells.

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Section: Discussionsupporting

confidence: 48%

Icariin induces MC3T3-E1 cell proliferation and differentiation via the BMP-2/Smads/Runx2 signal pathway

Gou

et al. 2018

Preprint

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“…On the other hand, both GH and IGF-1 increase the renal production of 1.25-(OH) 2 D (calcitriol) by enhancing the activity of renal 1 α -hydroxylase; the blood level of vitamin D is also affected [13]. According to the latest results, vitamin D supplementation increases the effect of recombinant human GH on bone formation in children with GHD, which can improve the effects of recombinant human GH therapy [14]. The aim of this study was to identify whether there is an association between hormonal therapy with GH, vitamin D 3 supplementation, vitamin D 3 levels, and the occurrence of caries among children affected by GHD.…”

Section: Introductionmentioning

confidence: 99%

Vitamin D₃ and Dental Caries in Children with Growth Hormone Deficiency

Wójcik

Szalewski

Pietryka-Michałowska

et al. 2019

International Journal of Endocrinology

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Vitamin D deficiency is a common risk factor for multifactorial diseases, and it seems to be associated with growth hormone deficiency (GHD). Vitamin D could prevent dental caries. The goal of this study was to identify whether there is an association between hormonal therapy with growth hormone (GH), vitamin D3 supplementation, vitamin D3 levels, and the occurrence of caries among children affected by GHD. The study group consisted of patients from the Department of Endocrinology and Diabetology of the University Paediatric Hospital at the Medical University of Lublin treated with recombinant human GH for pituitary GHD. It was conducted between October 2014 and June 2015. The study group included 121 children and adolescents aged 6 to 18 years, with 56 children from rural areas and 65 from urban areas. The study group was stratified by the area of residence. We found the statistically significant impact of vitamin D3 concentration on the average value of the DMFT (decayed, missed, and filled teeth) index and its component—DT (decayed teeth), which was noted in subjects from rural areas. Among patients from urban areas, we found a statistically significant correlation between duration of therapy and the DMFT index. An increase in duration of GH therapy by 10 months leads to a mean increase in DMFT index by 0.70. Based on multiple regression analysis, we developed the following model: value of DT = 3.10 − 0.73∗category of vitamin D3 concentration − 0.07∗duration of supplementation (in months). In this model, variables with a significant impact on the value of DT in the group of patients from rural areas include time of vitamin D3 supplementation and category of vitamin D3 concentration. Greater emphasis should be placed on promoting vitamin D3 as a potentially effective agent reducing the number of dental caries, especially among patients with GHD.

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“…It is a parameter strongly influenced by the GH/IGF-1 axis. Therefore, the finding of a relationship between this value and vitamin D supplementation in patients with GHD during rGH therapy confirmed the idea that vitamin D could have a reinforcing role on the effect of rGH therapy in such a population [75].…”

Section: Vitamin D Metabolism and Gh In Clinical Pediatric Studiesmentioning

confidence: 53%

Vitamin D and growth hormone in children: a review of the current scientific knowledge

et al. 2019

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BackgroundHuman growth is a complex mechanism that depends on genetic, environmental, nutritional and hormonal factors. The main hormone involved in growth at each stage of development is growth hormone (GH) and its mediator, insulin-like growth factor 1 (IGF-1). In contrast, vitamin D is involved in the processes of bone growth and mineralization through the regulation of calcium and phosphorus metabolism. Nevertheless, no scientific study has yet elucidated how they interact with one another, especially as a dysfunction in which one influences the other, even if numerous biochemical and clinical studies confirm the presence of a close relationship.Main bodyWe reviewed and analyzed the clinical studies that have considered the relationship between vitamin D and the GH/IGF-1 axis in pediatric populations. We found two main areas of interest: the vitamin D deficiency status in patients affected by GH deficit (GHD) and the relationship between serum vitamin D metabolites and IGF-1. Although limited by some bias, from the analysis of the studies presented in the scientific literature, it is possible to hypothesize a greater frequency of hypovitaminosis D in the subjects affected by GHD, a reduced possibility of its correction with only substitution treatment with recombinant growth hormone (rGH) and an improvement of IGF-1 levels after supplementation treatment with vitamin D.ConclusionsThese results could be followed by preventive interventions aimed at reducing the vitamin D deficit in pediatric age. In addition, further research is needed to fully understand how vitamin D and growth are intertwined.

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The relationships of alkaline phosphatase and bone alkaline phosphatase to the growth hormone/insulin-like growth factor-1 axis and vitamin D status in children with growth hormone deficiency

Cited by 9 publications

References 41 publications

Icariin induces MC3T3-E1 cell proliferation and differentiation via the BMP-2/Smads/Runx2 signal pathway

Icariin induces MC3T3-E1 cell proliferation and differentiation via the BMP-2/Smads/Runx2 signal pathway

Vitamin D₃ and Dental Caries in Children with Growth Hormone Deficiency

Vitamin D and growth hormone in children: a review of the current scientific knowledge

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The relationships of alkaline phosphatase and bone alkaline phosphatase to the growth hormone/insulin-like growth factor-1 axis and vitamin D status in children with growth hormone deficiency

Cited by 9 publications

References 41 publications

Icariin induces MC3T3-E1 cell proliferation and differentiation via the BMP-2/Smads/Runx2 signal pathway

Icariin induces MC3T3-E1 cell proliferation and differentiation via the BMP-2/Smads/Runx2 signal pathway

Vitamin D3 and Dental Caries in Children with Growth Hormone Deficiency

Vitamin D and growth hormone in children: a review of the current scientific knowledge

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Vitamin D₃ and Dental Caries in Children with Growth Hormone Deficiency