Urinary Silicon Excretion in Relation to Lactation and Bone Mineral Density - a Longitudinal Study Post-partum.

Silicon (Si) may be a mineral beneficial for bone health. Pregnancy and lactation have major impacts on maternal bone metabolism as bone minerals, including calcium (Ca), are required for growth of the foetus and for milk production. Like urinary Ca excretion, Si excretion has been reported to be high in pregnant women, but there are no data post-partum and during lactation. The aim of the present study was to investigate the urinary excretion of Si (U-Si), from the third trimester of pregnancy until 18 months post-partum, and in relation to the length of lactation, to determine if changes in U-Si are associated with changes in areal bone mineral density (aBMD). This longitudinal study included 81 pregnant women, of whom 56 completed the study. Spot urine samples were collected at the third trimester and at 0.5, 4, 12, and 18 months post-partum and were analysed for Si and Ca by ICP-OES. The aBMD was measured post-partum at lumbar spine and femoral neck by dual-energy x-ray absorptiometry. Women lactating for 4-8.9 and ≥ 9 months had significantly higher U-Si at 4 months post-partum, compared with the third trimester. No significant longitudinal differences in U-Si were found after correcting for creatinine. Changes in U-Si and in aBMD were not correlated, except at the lumbar spine from 0.5 to 12 months post-partum in the women lactating for 4-8.9 months. Taken together, our results suggest that there is a possibility that U-Si increases post-partum in women lactating for 4 months or longer, although it is not related to changes in aBMD.

Inhibitory effects of orthosilicic acid on osteoclastogenesis in RANKL-stimulated RAW264.7 cells.

Numerous studies have reported on the positive effects of silicon (Si) on bone metabolism, particularly on the stimulatory effects of Si on osteoblast cells and on bone formation. Inhibitory effects of Si on osteoclast formation and bone resorption have also been demonstrated in vitro and are suggested to be mediated indirectly via stromal and osteoblast cells. Direct effects of Si on osteoclasts have been less studied and mostly using soluble Si, but no characterisation of the Si treatment solutions are provided. The aims of the present study were to (a) further investigate the direct inhibitory effects of Si on osteoclastogenesis in RANKL-stimulated RAW264.7 cells, (b) determine at what stage during osteoclastogenesis Si acts upon, and (c) determine if these effects can be attributed to the biologically relevant soluble orthosilicic acid specie. Our results demonstrate that silicon, at 50 µg/ml (or 1.8 mM), does not affect cell viability but directly inhibits the formation of TRAP+ multinucleated cells and the expression of osteoclast phenotypic genes in RAW264.7 cells. The inhibitory effect of Si was clearly associated with the early stages (first 24 hr) of osteoclastogenesis. Moreover, these effects can be attributed to the soluble orthosilicic acid specie.

Soluble silica stimulates osteogenic differentiation and gap junction communication in human dental follicle cells.

Several studies have indicated that dietary silicon (Si) is beneficial for bone homeostasis and skeletal health. Furthermore, Si-containing bioactive glass biomaterials have positive effects on bone regeneration when used for repair of bone defects. Si has been demonstrated to stimulate osteoblast differentiation and bone mineralisation in vitro. However, the mechanisms underlying these effects of Si are not well understood. The aim of the present study was to investigate the effects of soluble Si on osteogenic differentiation and connexin 43 (CX43) gap junction communication in cultured pluripotent cells from human dental follicles (hDFC). Neutral Red uptake assay demonstrated that 25 µg/ml of Si significantly stimulated hDFC cell proliferation. Dosages of Si above 100 µg/ml decreased cell proliferation. Alizarin Red staining showed that osteogenic induction medium (OIM) by itself and in combination with Si (25 µg/ml) significantly increased mineralisation in hDFC cultures, although Si alone had no such effect. The expression of osteoblast-related markers in hDFC was analysed with RT-qPCR. OSX, RUNX2, BMP2, ALP, OCN, BSP and CX43 genes were expressed in hDFC cultured for 1, 7, 14 and 21 days. Expression levels of BMP-2 and BSP were significantly upregulated by OIM and Si (25 µg/ml) and were also induced by Si alone. Notably, the expression levels of OCN and CX43 on Day 21 were significantly increased only in the Si group. Flow cytometric measurements revealed that Si (50 µg/ml) significantly increased CX43 protein expression and gap junction communication in hDFC. Next-generation sequencing (NGS) and bioinformatics processing were used for the identification of differentially regulated genes and pathways. The influence of OIM over the cell differentiation profile was more prominent than the influence of Si alone. However, Si in combination with OIM increased the magnitude of expression (up or down) of the differentially regulated genes. The gene for cartilage oligomeric matrix protein (COMP) was the most significantly upregulated. Genes for the regulator of G protein signalling 4 (RGS4), regulator of G protein signalling 2 (RGS2), and matrix metalloproteinases (MMPs) 1, 8, and 10 were also strongly upregulated. Our findings reveal that soluble Si stimulates Cx43 gap junction communication in hDFC and induces gene expression patterns associated with osteogenic differentiation. Taken together, the results support the conclusion that Si is beneficial for bone health.

Urinary Excretion of Silicon in Men, Non-pregnant Women, and Pregnant Women: a Cross-sectional Study.

Silicon is a trace element found mainly in plant-based food and proposed to be beneficial for bone health. Urinary excretion of Si has been shown to be a surrogate measure of its uptake in the gastrointestinal tract. The objective of this study was to describe and compare the levels of urinary Si excretion, and consequently Si uptake, in Swedish men, non-pregnant women, and pregnant women. No formal assessment of dietary Si intake was carried out in this study. This cross-sectional study included 89 men, 42 non-pregnant women, and 60 pregnant women. The subjects collected urine over a 24-h period and the samples were assayed for total Si using inductively coupled plasma optical emission spectrometry. The excretion levels of creatinine were used to validate the completeness of the urine sample collections. The mean 24-h urinary excretions of Si were 7.8 mg for the cohort of young men, 7.6 mg for the cohort of non-pregnant women, and 12.4 mg for the cohort of pregnant women. Creatinine excretion was similar between pregnant and non-pregnant women (10.4 vs. 10.8 mmol/day) and significantly higher in men (15.4 mmol/day). The pregnant women excreted significantly higher levels of Si than the young men and non-pregnant women, respectively (p < 0.05). The higher urinary excretion of Si by pregnant women compared with men and non-pregnant women is a novel finding possibly caused by temporary physiological changes during pregnancy such as increased gastrointestinal uptake of Si, altered bone metabolism, and increased renal excretion of Si.