Category Archives: Supplements

Taurine Inhibits Osteoblast Apoptosis in Mouse Cells

Abstract

Taurine inhibits serum deprivation-induced osteoblast apoptosis via the taurine transporter/ERK signaling pathway.

Taurine has positive effects on bone metabolism. However, the effects of taurine on osteoblast apoptosis in vitro have not been reported. The aim of this study was to investigate the activity of taurine on apoptosis of mouse osteoblastic MC3T3-E1 cells. The data showed that 1, 5, 10, or 20 mM taurine resulted in 16.7, 34.2, 66.9, or 63.75% reduction of MC3T3-E1 cell apoptosis induced by the serum deprivation (serum-free α-MEM), respectively. Taurine (1, 5, or 10 mM) also reduced cytochrome c release and inhibited activation of caspase-3 and -9, which were measured using fluorogenic substrates for caspase-3/caspase-9, in serum-deprived MC3T3-E1 cells. Furthermore, taurine (10 mM) induced extracellular signal-regulated kinase (ERK) phosphorylation in MC3T3-E1 cells. Knockdown of the taurine transporter (TAUT) or treatment with the ERK-specific inhibitor PD98059 (10 μM) blocked the activation of ERK induced by taurine (10 mM) and abolished the anti-apoptotic effect of taurine (10 mM) in MC3T3-E1 cells. The present results demonstrate for the first time that taurine inhibits serum deprivation-induced osteoblast apoptosis via the TAUT/ERK signaling pathway.

Zhang LY, Zhou YY, Chen F, Wang B…
Braz. J. Med. Biol. Res. Jul 2011
PMID: 21710101 | Free Full Text

Taurine Increases Bone Density in Rats

Abstract

The effects of dietary taurine supplementation on bone mineral density in ovariectomized rats.

This study was performed to evaluate the effect of a diet rich in taurine (2.0 g/100 g) on bone metabolism in ovariectomized (OVX) rats. All rats were fed deionized water during the experimental period. Bone mineral density (BMD) and bone mineral content (BMC) of spine and femur were measured. Serum and urinary calcium and phosphorus content were determined. The levels serum osteocalcin and alkaline phosphatase (ALP) were used to assess bone formation. The rate of bone resorption was measured by the deoxypyridinoline (DPD) crosslink immunoassay and corrected for creatinine. Urinary Ca and P excretion, serum osteocalcin content, and the crosslink value were not significantly different between the Sham groups. The taurine supplemented, Sham group had higher spinal and femur BMC than those of the untreated control group, but the difference was not statistically significant. However, the taurine supplemented, Sham group had significantly higher spine and femur BMC per weight than those of the untreated control group. Within the OVX group, the taurine supplemented group had a lower crosslink value than the casein group. The taurine supplemented, OVX group had higher femur bone mineral content per weight than those of the control, OVX group, but the difference was not statistically significant. A study examining the long-term effect of taurine supplementation in humans is warranted.

Choi MJ, DiMarco NM
Adv. Exp. Med. Biol. 2009
PMID: 19239165

Review: Nutrients Involved in Maintaining Healthy Bone

Abstract

Update on nutrients involved in maintaining healthy bone.

Osteoporosis is a leading cause of morbidity and mortality in the elderly and influences quality of life, as well as life expectancy. Currently, there is a growing interest among the medical scientists in search of specific nutrients and/or bioactive compounds of natural origin for the prevention of disease and maintenance of bone health. Although calcium and vitamin D have been the primary focus of nutritional prevention of osteoporosis, a recent research has clarified the importance of several additional nutrients and food constituents. Based on this review of the literature, supplementation with vitamins B, C, K, and silicon could be recommended for proper maintenance of bone health, although further clinical studies are needed. The results of studies on long-chain polyunsaturated fatty acids, potassium, magnesium, copper, selenium, and strontium are not conclusive, although studies in vitro and in animal models are interesting and promising.

Rondanelli M, Opizzi A, Perna S, Faliva MA
Endocrinol Nutr Apr 2013
PMID: 23273614

D-Pinitol Inhibits Osteoclasts in Rats

Abstract

D-pinitol inhibits RANKL-induced osteoclastogenesis.

Numerous studies have indicated that inflammatory cytokines play a major role in osteoclastogenesis, leading to the bone resorption that is frequently associated with osteoporosis. D-pinitol, a 3-methoxy analogue of D-chiroinositol, was identified as an active principle in soy foods and legumes. Here we found that D-pinitol markedly inhibited the receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastic differentiation from bone marrow stromal cells and RAW264.7 macrophage cells. In addition, D-pinitol also reduced RANKL-induced p38 and JNK phosphorylation. Furthermore, RANKL-mediated increase of IKK, IκBα, and p65 phosphorylation and NF-κB-luciferase activity was inhibited by D-pinitol. However, D-pinitol did not affect the proliferation and differentiation of osteoblasts. In addition, D-pinitol also prevented the bone loss induced by ovariectomy in vivo. Our data suggest that D-pinitol inhibits osteoclastogenesis from bone marrow stromal cells and macrophage cells via attenuated RANKL-induced p38, JNK, and NF-κB activation, which in turn protect bone loss from ovariectomy.

Liu SC, Chuang SM, Tang CH
Int. Immunopharmacol. Mar 2012
PMID: 22269833

D-Chiro-Inositol Inhibits Osteoclasts In Vitro

Abstract

D-chiro-inositol negatively regulates the formation of multinucleated osteoclasts by down-regulating NFATc1.

Osteoclasts (OCs) are multinucleated giant cells that resorb bone matrix. Accelerated bone destruction by OCs might cause several metabolic bone-related diseases, such as osteoporosis and inflammatory bone loss. D-pinitol (3-O-methyl-D-chiro-inositol) is a prominent component of dietary legumes and is actively converted to D-chiro-inositol, which is a putative insulin-like mediator. In this study, we analyzed the effect of D-chiro-inositol on OC differentiation.
To analyze the role of D-chiro-inositol on OC differentiation, we examined OC differentiation by the three types of osteoclastogenesis cultures with tartrate-resistant acid phosphatase (TRAP) staining and solution assay. Then, we carried out cell fusion assay with purified TRAP(+) mononuclear OC precursors. Finally, we analyzed the effect of D-chiro-inositol on OC maker expression in response to the regulation of nuclear factor of activated T cells c1 (NFATc1).
We demonstrated that D-chiro-inositol acts as an inhibitor of receptor activator of NF-κB ligand-induced OC differentiation. The formation of multinucleated OCs by cell-cell fusion is reduced by treatment with D-chiro-inositol in a dose-dependent manner. In addition, we demonstrated that D-chiro-inositol inhibits the expression of several osteoclastogenic genes by down-regulating NFATc1.
We have shown that D-chiro-inositol is negatively involved in osteoclastogenesis through the inhibition of multinucleated OC formation by cell-cell fusion. The expression of NFATc1 was significantly down-regulated by D-chiro-inositol in OCs and consequently, the expression of OC marker genes was significantly reduced. Hence, these results show that D-chiro-inositol might be a good candidate to treat inflammatory bone-related diseases or secondary osteoporosis in diabetes mellitus.

Yu J, Choi S, Park ES, Shin B…
J. Clin. Immunol. Dec 2012
PMID: 22711011

Phytate Associated with Reduced Bone Loss and Fractures in Postmenopausal Women

Abstract

Protective effect of myo-inositol hexaphosphate (phytate) on bone mass loss in postmenopausal women.

The objective of this paper was to evaluate the relationship between urinary concentrations of InsP6, bone mass loss and risk fracture in postmenopausal women.
A total of 157 postmenopausal women were included in the study: 70 had low (≤0.76 μM), 42 intermediate (0.76-1.42 μM) and 45 high (≥1.42 μM) urinary phytate concentrations. Densitometry values for neck were measured at enrollment and after 12 months (lumbar spine and femoral neck), and 10-year risk fracture was calculated using the tool FRAX(®).
Individuals with low InsP6 levels had significantly greater bone mass loss in the lumbar spine (3.08 ± 0.65 % vs. 0.43 ± 0.55 %) than did those with high phytate levels. Moreover, a significantly greater percentage of women with low than with high InsP6 levels showed more than 2 % of bone mass loss in the lumbar spine (55.6 vs. 20.7 %). The 10-year fracture probability was also significantly higher in the low-phytate group compared to the high-phytate group, both in hip (0.37 ± 0.06 % vs 0.18 ± 0.04 %) and major osteoporotic fracture (2.45 ± 0.24 % vs 1.83 ± 0.11 %).
It can be concluded that high urinary phytate concentrations are correlated with reduced bone mass loss in lumbar spine over 12 months and with reduced 10-year probability of hip and major osteoporotic fracture, indicating that increased phytate consumption can prevent development of osteoporosis.

López-González AA, Grases F, Monroy N, Marí B…
Eur J Nutr Mar 2013
PMID: 22614760

IP-6 Inhibits Osteoclastogenesis and Increases Resorption of Mature Osteoclasts In Vitro

Abstract

Inositol hexakisphosphate inhibits osteoclastogenesis on RAW 264.7 cells and human primary osteoclasts.

Inoxitol hexakisphosphate (IP6) has been found to have an important role in biomineralization and a direct effect inhibiting mineralization of osteoblasts in vitro without impairing extracellular matrix production and expression of alkaline phosphatase. IP6 has been proposed to exhibit similar effects to those of bisphosphonates on bone resorption, however, its direct effect on osteoclasts (OCL) is presently unknown. The aim of the present study was to investigate the effect of IP6 on the RAW 264.7 monocyte/macrophage mouse cell line and on human primary osteoclasts. On one hand, we show that IP6 decreases the osteoclastogenesis in RAW 264.7 cells induced by RANKL, without affecting cell proliferation or cell viability. The number of TRAP positive cells and mRNA levels of osteoclast markers such as TRAP, calcitonin receptor, cathepsin K and MMP-9 was decreased by IP6 on RANKL-treated cells. On the contrary, when giving IP6 to mature osteoclasts after RANKL treatment, a significant increase of bone resorption activity and TRAP mRNA levels was found. On the other hand, we show that 1 µM of IP6 inhibits osteoclastogenesis of human peripheral blood mononuclear cells (PBMNC) and their resorption activity both, when given to undifferentiated and to mature osteoclasts.
Our results demonstrate that IP6 inhibits osteoclastogenesis on human PBMNC and on the RAW264.7 cell line. Thus, IP6 may represent a novel type of selective inhibitor of osteoclasts and prove useful for the treatment of osteoporosis.

Arriero Mdel M, Ramis JM, Perelló J, Monjo M
PLoS ONE 2012
PMID: 22905230 | Free Full Text

IP-6 Effects on Osteoblasts are Complicated

Abstract

Differential response of MC3T3-E1 and human mesenchymal stem cells to inositol hexakisphosphate.

Inositol hexakisphosphate (IP6) has been found to have an important role in biomineralization. Because the complete mechanism of action of IP6 on osteoblasts is not fully understood and its potential use in the primary prevention of osteoporosis, we examined the direct effect of IP6 on cell viability and differentiation of MC3T3-E1 cells and on differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs). We show that IP6 has different effects depending on the origin of the cell target. Thus, while IP6 decreased gene expression of osteoblast markers and mineralization in MC3T3-E1 cells without negatively affecting cell viability and ALP activity, an increase in gene expression of ALP was observed in hUC-MSCs committed to the osteoblastic lineage. This increasing effect of IP6 on ALP mRNA expression levels was reversed by the addition of a selective inhibitor of IP6 kinase, suggesting that the effect of IP6 might be due through its pyrophosphorylated derivatives. Besides, Rankl mRNA levels were decreased after IP6 treatment in MC3T3-E1 cells, pointing to a paracrine effect on osteoclasts.
Our results indicate that IP6 has different effects on osteoblast differentiation depending on the cell type and origin. However, further studies are needed to examine the net effect of IP6 on bone formation and its potential as novel antiosteoporosis drug.

Arriero Mdel M, Ramis JM, Perelló J, Monjo M
Cell. Physiol. Biochem. 2012
PMID: 23221481

IP-6 May Impair Bioavailability of Iron, Calcium, and Zinc in Chinese

Abstract

Phytate intake and molar ratios of phytate to zinc, iron and calcium in the diets of people in China.

To assess the phytate intake and molar ratios of phytate to calcium, iron and zinc in the diets of people in China.
2002 China Nationwide Nutrition and Health Survey is a cross-sectional nationwide representative survey on nutrition and health. The information on dietary intakes was collected using consecutive 3 days 24 h recall by trained interviewers.
The data of 68 962 residents aged 2-101 years old from 132 counties were analyzed.
The median daily dietary intake of phytate, calcium, iron and zinc were 1186, 338.1, 21.2 and 10.6 mg, respectively. Urban residents consumed less phytate (781 vs 1342 mg/day), more calcium (374.5 vs 324.1 mg/day) and comparable amounts of iron (21.1 vs 21.2 mg/day) and zinc (10.6 vs 10.6 mg/day) than their rural counterparts. A wide variation in phytate intake among residents from six areas was found, ranging from 648 to 1433 mg/day. The median molar ratios of phytate to calcium, iron, zinc and phytate x calcium/zinc were 0.22, 4.88, 11.1 and 89.0, respectively, with a large variation between urban and rural areas. The phytate:zinc molar ratios ranged from 6.2 to 14.2, whereas the phytate x calcium/zinc molar ratios were from 63.7 to 107.2. The proportion of subjects with ratios above the critical values of phytate to iron, phytate to calcium, phytate to zinc and phytate x calcium/zinc were 95.4, 43.7, 23.1 and 8.7%, respectively. All the phytate/mineral ratios of rural residents were higher than that of their urban counterparts.
The dietary phytate intake of people in China was higher than those in Western developed countries and lower than those in developing countries. Phytate may impair the bioavailability of iron, calcium and zinc in the diets of people in China.

Ma G, Li Y, Jin Y, Zhai F…
Eur J Clin Nutr Mar 2007
PMID: 16929240

IP-6 Supplementation Causes Thinner Bones in Rats

Abstract

Bone and faecal minerals and scanning electron microscopic assessments of femur in rats fed phytic acid extract from sweet potato (Ipomoea batatas).

Phytic acid was extracted from sweet potato (Ipomoea batatas) and fed to Wistar rats with or without zinc for 3 weeks. Animals were then sacrificed and bone and faecal minerals were assessed. The ultra-structure of the bones was examined via scanning electron microscopy. Phytic acid extract or commercial phytic acid supplemented diets (D + Zn + PE or D + PE) displayed reduced bone calcium levels (101.27 +/- 59.11 and 119.27 +/- 45.36 g/kg) compared to the other test groups. Similarly, reduced calcium were observed in the control groups (D + Zn and D) fed formulated diets with or without zinc supplementation (213.14 +/- 15.31 and 210 +/- 6.88 g/kg) compared to the other test groups. The group fed supplemented commercial phytic acid diet (D + CP) demonstrated the lowest femur magnesium (3.72 +/- 0.13 g/kg) while the group fed phytic acid extract supplementation (D + PE) recorded the highest level (4.84 +/- 0.26 g/kg) amongst the groups. Femur iron was highest in the group fed commercial phytic acid supplemented diet (D + CP -115.74 +/- 2.41 g/kg) compared to the other groups. Faecal magnesium levels were significantly higher in the two test groups fed phytic acid extract with or without zinc (D + Zn + PE or D + PE) compared to all other groups. All the groups which had phytic acid supplemented diets had significantly thinner bone in the trabecular region, compared to the groups fed formulated diet or zinc supplemented formulated diet (D or D + Zn). These observations suggest that the consumption of foods high in phytic acid may contribute to a reduction in the minerals available for essential metabolic processes in rats.

Dilworth L, Omoruyi FO, Reid W, Asemota HN
Biometals Apr 2008
PMID: 17562130