Category Archives: Supplements

Inositol is Essential for Osteogenesis and Bone Formation in Mice

Abstract

Sodium/myo-inositol cotransporter 1 and myo-inositol are essential for osteogenesis and bone formation.

myo-Inositol (MI) plays an essential role in several important processes of cell physiology, is involved in the neural system, and provides an effective treatment for some psychiatric disorders. Its role in osteogenesis and bone formation nonetheless is unclear. Sodium/MI cotransporter 1 (SMIT1, the major cotransporter of MI) knockout (SMIT1(-/-)) mice with markedly reduced tissue MI levels were used to characterize the essential roles of MI and SMIT1 in osteogenesis. SMIT1(-/-) embryos had a dramatic delay in prenatal mineralization and died soon after birth owing to respiratory failure, but this could be rescued by maternal MI supplementation. The rescued SMIT1(-/-) mice had shorter limbs, decreased bone density, and abnormal bone architecture in adulthood. Deletion of SMIT1 resulted in retarded postnatal osteoblastic differentiation and bone formation in vivo and in vitro. Continuous MI supplementation partially restored the abnormal bone phenotypes in adult SMIT1(-/-) mice and strengthened bone structure in SMIT1(+/+) mice. Although MI content was much lower in SMIT1(-/-) mesenchymal cells (MSCs), the I(1,4,5)P(3) signaling pathway was excluded as the means by which SMIT1 and MI affected osteogenesis. PCR expression array revealed Fgf4, leptin, Sele, Selp, and Nos2 as novel target genes of SMIT1 and MI. SMIT1 was constitutively expressed in multipotential C3H10T1/2 and preosteoblastic MC3T3-E1 cells and could be upregulated during bone morphogenetic protein 2 (BMP-2)-induced osteogenesis. Collectively, this study demonstrated that deficiency in SMIT1 and MI has a detrimental impact on prenatal skeletal development and postnatal bone remodeling and confirmed their essential roles in osteogenesis, bone formation, and bone mineral density (BMD) determination.

Dai Z, Chung SK, Miao D, Lau KS…
J. Bone Miner. Res. Mar 2011
PMID: 20818642

Furosin Suppresses Osteoclasts in Mouse Cells

Abstract

Furosin, an ellagitannin, suppresses RANKL-induced osteoclast differentiation and function through inhibition of MAP kinase activation and actin ring formation.

Phenolic compounds including tannins and flavonoids have been implicated in suppression of osteoclast differentiation/function and prevention of bone diseases. However, the effects of hydrolysable tannins on bone metabolism remain to be elucidated. In this study, we found that furosin, a hydrolysable tannin, markedly decreased the differentiation of both murine bone marrow mononuclear cells and Raw264.7 cells into osteoclasts, as revealed by the reduced number of tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells and decreased TRAP activity. Furosin appears to target at the early stage of osteoclastic differentiation while having no cytotoxic effect on osteoclast precursors. Analysis of the inhibitory mechanisms of furosin revealed that it inhibited the receptor activator of nuclear factor-kappaB ligand (RANKL)-induced activation of p38 mitogen-activated protein kinase (p38MAPK) and c-Jun N-terminal kinase (JNK)/activating protein-1 (AP-1). Furthermore, furosin reduced resorption pit formation in osteoclasts, which was accompanied by disruption of the actin rings. Taken together, these results demonstrate that naturally occurring furosin has an inhibitory activity on both osteoclast differentiation and function through mechanisms involving inhibition of the RANKL-induced p38MAPK and JNK/AP-1 activation as well as actin ring formation.

Park EK, Kim MS, Lee SH, Kim KH…
Biochem. Biophys. Res. Commun. Dec 2004
PMID: 15555594

Ellagic Acid May Be a Natural SERM

Abstract

Evaluation of estrogenic/antiestrogenic activity of ellagic acid via the estrogen receptor subtypes ERalpha and ERbeta.

Ellagic acid is a plant-derived polyphenol, possessing antioxidant, antiproliferative, and antiatherogenic properties. Whether this compound has estrogenic/antiestrogenic activity, however, remains largely unknown. To answer this question, we first investigated the ability of ellagic acid to influence the activity of the estrogen receptor subtypes ERalpha and ERbeta in HeLa cells. Cells co-transfected with an estrogen response element (ERE)-driven luciferase (Luc) reporter gene and an ERalpha- or ERbeta-expression vector were exposed to graded concentrations of ellagic acid. At low concentrations (10(-7) to 10(-9) M), this compound displayed a small but significant estrogenic activity via ERalpha, whereas it was a complete estrogen antagonist via ERbeta. Further evaluation revealed that ellagic acid was a potent antiestrogen in MCF-7 breast cancer-derived cells, increasing, like the pure estrogen antagonist ICI182780, IGFBP-3 levels. Moreover, ellagic acid induced nodule mineralization in an osteoblastic cell line (KS483), an effect that was abolished by the estrogen antagonist. Endometrium-derived epithelial cells (Ishikawa) showed no response to the natural compound by using a cell viability assay (MTT). These findings suggest that ellagic acid may be a natural selective estrogen receptor modulator (SERM).

Papoutsi Z, Kassi E, Tsiapara A, Fokialakis N…
J. Agric. Food Chem. Oct 2005
PMID: 16190622

TMG No Benefit for Bones in Homocystinuria

Abstract

The effect of oral betaine on vertebral body bone density in pyridoxine-non-responsive homocystinuria.

Five pyridoxine-non-responsive homocystinuric patients aged 5 to 32 years were treated with oral betaine, 3 g b.i.d, in a double-blind, placebo-controlled, two-year crossover study of its effect on bone mineralization. Betaine therapy significantly reduced mean plasma homocystine (36 +/- 9 (SEM) mumol L-1 to 9 +/- 4 mumol L-1), with variable increases in plasma methionine and no adverse effects. Bone density, measured by computerized tomographic scanning of vertebral bodies, was below normal in all patients at the start of the study, and was not significantly altered by betaine therapy administered according to this protocol.

Gahl WA, Bernardini I, Chen S, Kurtz D…
J. Inherit. Metab. Dis. 1988
PMID: 3148071

Why is this interesting? It’s interesting because several studies show an association between homocysteine and osteoporosis. TMG is known to lower homocysteine. Yet, in this study, there was no increase in bone density despite homocysteine being cut 75%.

Xylitol Improves Bone Strength, Elasticity, and Volume in Rats

Abstract

Improved bone biomechanical properties in rats after oral xylitol administration.

The effects of 5, 10, and 20% dietary xylitol supplementations on the biomechanical properties, histological architecture, and the contents of collagen, pyridinoline, and deoxypyridinoline in long bones of rats were studied. Tibiae were used for the three-point bending test, and femurs were used for the torsion and loading test of the femoral neck. The 10 and 20% oral xylitol administrations caused a significant increase of tibial stress, femoral shear stress, and stress of the femoral neck as compared with the controls. Parallel, but not significant, effects were also seen in the 5% xylitol supplementation group. No significant differences in strain or Young’s modulus of the tibiae were detected between the groups. An increased shear modulus of elasticity in femurs was detected in the 20% supplementation group as compared with the controls. The histomorphometrical data for the secondary spongiosa of the proximal tibia revealed that trabecular bone volume was significantly greater in all dietary xylitol supplementation groups as compared with the controls. The bone volume increased along with increasing xylitol content. No significant differences between the groups were detected concerning the amount of collagen per dry weight of organic matrix, the concentrations of pyridinoline or deoxypyridinoline in collagen, or the ratio of these crosslinks. This suggests no xylitol-dependent selective changes in these structures of bone collagen. In conclusion, dietary xylitol supplementation in rats improves the biomechanical properties of bone and increases the trabecular bone volume dose dependently.

Mattila P, Knuuttila M, Kovanen V, Svanberg M
Calcif. Tissue Int. Apr 1999
PMID: 10089228

Xylitol Improves Bone Strength in Rats

Abstract

Improved bone biomechanical properties in xylitol-fed aged rats.

Our previous studies have shown that dietary xylitol protects against weakening of bone biomechanical properties in experimental postmenopausal osteoporosis. To study whether xylitol preserves bone biomechanics also during aging, a long-term experimental study was performed with rats. Twenty-four male Sprague-Dawley rats were divided into 2 groups. The rats in the control group (NON-XYL group) were fed a basal rat and mouse no. 1 maintenance (RM1) diet, while the rats in the experimental group (XYL group) were continuously fed the same diet supplemented with 10% xylitol (wt/wt). The rats were killed after 20 months. Their femurs were prepared for biomechanical analyses and scanning analyses with peripheral quantitative computed tomography (pQCT). In 3-point bending of the femoral diaphysis, maximum load, maximum elastic load, stiffness, energy absorption, elastic energy absorption, ultimate stress, and yield stress were significantly greater in the XYL group than in the NON-XYL group. This indicates a xylitol-induced improvement of both structural and material strength properties of cortical bone. Accordingly, the maximum load of femoral neck was significantly greater in the XYL group. In the pQCT analysis of femoral diaphysis, cortical bone area, cortical thickness (CtTh) periosteal circumference, and cross-sectional moment of inertia were greater in the XYL group. The endosteal circumference was smaller in the XYL group. In the pQCT analysis of the femoral neck cortical area of the midneck was significantly greater in the XYL group. This data indicates that xylitol exerted beneficial effects on the cross-sectional architecture of the bones. In conclusion, continuous moderate dietary xylitol supplementation leads to improved bone biomechanical properties in aged rats concerning both bone structural and material strength properties.

Mattila PT, Svanberg MJ, Jämsä T, Knuuttila ML
Metab. Clin. Exp. Jan 2002
PMID: 11782878

Xylitol + Alcohol > Xylitol Alone For Bone Resorption and Density in Rats

Abstract

The effect of a simultaneous dietary administration of xylitol and ethanol on bone resorption.

Our previous studies have shown that dietary xylitol supplementation diminishes bone resorption in rats, as well as protects against ovariectomy-induced increase of bone resorption during experimental osteoporosis. Interestingly, ethanol, when given simultaneously with xylitol, is known to increase blood concentration of xylitol. On the other hand, ethanol, when given alone, has been shown to increase bone resorption. The aim of the present study was to evaluate the effects of a simultaneous dietary administration of 10% xylitol and 10% ethanol on bone resorption. Bone resorption was determined using measurement of urinary excretion of hydrogen 3 (3H) radioactivity in 3H-tetracycline prelabeled rats. Already 4 days after the beginning of dietary supplementations, excretion of 3H was about 15% lower in the xylitol group (diet supplemented with 10% xylitol) and about 25% lower in the xylitol-ethanol group (diet supplemented with 10% xylitol and 10% ethanol) as compared to the controls. The excretion of 3H in these groups remained smaller than that of the controls throughout the entire study period of 40 days. The excretion of 3 H in the xylitol-ethanol group remained also smaller than that of the xylitol group. Bone mineral density and bone mineral content were determined with a peripheral quantitative computed tomography (pQCT) system from the rat tibiae at the end of the experiment. Trabecular bone mineral density and trabecular bone mineral content were significantly greater in the xylitol group and in the xylitol-ethanol group compared to the controls. They were also greater in the xylitol-ethanol group as compared to the xylitol group. Cortical bone mineral density and cortical bone mineral content did not differ significantly between the groups. In conclusion, a simultaneous dietary supplementation with 10% xylitol and 10% ethanol seems to diminish bone resorption and to increase trabecular bone mineral density and trabecular bone mineral content in rats. These effects seem to be stronger than the effects induced by 10% xylitol supplementation alone.

Mattila PT, Kangasmaa H, Knuuttila ML
Metab. Clin. Exp. Apr 2005
PMID: 15798965

Xylitol Protects Bone in Arthritic Rats

Abstract

Dietary xylitol protects against the imbalance in bone metabolism during the early phase of collagen type II-induced arthritis in dark agouti rats.

The aim of the present study was to evaluate the changes in bone metabolism during the early phase of type II collagen-induced arthritis in rats and to evaluate whether a 10% dietary xylitol supplementation is able to protect against these changes. Arthritis was induced in female dark agouti rats by injections of type II homologous rat collagen emulsified with an equal volume of incomplete Freund adjuvant. In one group, the diet was supplemented with 10% xylitol. After 17 days, the rats were killed. Serum osteocalcin, as a marker of bone formation, and serum tartrate-resistant acid phosphatase, as a marker of bone resorption, were measured. Histologic measurements were made from Masson-Goldner trichrome-stained sections of distal tibiae. All the collagen-injected rats had arthritic symptoms at the end of the experiment. Serum osteocalcin was significantly higher in the collagen-injected rats fed a xylitol-supplemented diet (CI-X) than in the collagen-injected rats not fed xylitol (CI) and in the controls. Serum tartrate-resistant acid phosphatase was significantly higher in the CI and CI-X groups than in the controls. Trabecular bone volume was significantly lower in the CI group as compared with the CI-X and control groups. These results suggest that, at the time of the appearance of arthritic symptoms, bone resorption activity is high, but bone formation is not severely affected. Furthermore, dietary xylitol seems to protect against the imbalance of bone metabolism during the early phase of collagen type II-induced arthritis.

Kaivosoja SM, Mattila PT, Knuuttila ML
Metab. Clin. Exp. Aug 2008
PMID: 18640381

Xylitol Increases Bone Density in Rat Femur

Abstract

The effects of oral xylitol administration on bone density in rat femur.

To examine the effects of oral xylitol administration on rat femur bone density, 36 four-week-old male Wistar rats divided into three groups were fed CE-2 diet (control, n = 12) alone or supplemented with 10% (n = 12) or 20% (n = 12) dietary xylitol for 40 days. Biochemical, morphological, and histological analyses were performed. The 10% and 20% xylitol groups showed higher levels of both serum Ca and alkaline phosphatase activity and lower levels of serum tartrate-resistant acid phosphatase than the control group. Although no significant differences in the three-dimensional bone structure or trabecular bone structure of the femur were observed, both xylitol groups showed significantly higher bone density than the control group. Compared to the control group, the 10% and 20% xylitol groups showed an increase in trabeculae. Thus, oral administration of xylitol appears to affect bone metabolism, leading to increased bone density in rat femur.

Sato H, Ide Y, Nasu M, Numabe Y
Odontology Jan 2011
PMID: 21271323

Xylitol Preserves Bone in Ovariectomized Rats

Abstract

Dietary xylitol protects against weakening of bone biomechanical properties in ovariectomized rats.

The effects of dietary xylitol (xyl) on bone biomechanical properties in ovariectomized rats (ovx) were studied. Forty-two 3-mo-old female Wistar rats were divided into three groups of 14. Rats in two groups were ovariectomized, while those in the control group underwent a sham operation. All rats received a basal diet, and half of the ovx were given an additional 10 g/100 g dietary xyl supplementation. Three months later the rats were killed and their tibias, femurs and humeri were prepared. The tibias were used for analyses of bone density and trabecular bone volume (BV/TV) and for the three-point bending test. The femurs were used for the torsion test and for the loading test of the femoral neck. The humeri were used for analyses of bone ash weight and bone concentrations of calcium and phosphorus. Dietary xyl gave a significant protection against ovariectomy-caused decline of tibial stress in the three-point bending test, of femoral shear stress in the torsion test, and of stress of the femoral neck, without affecting bone elasticity values. Xyl restricted the ovariectomy-caused reduction in bone density, in bone ash weight and in concentrations of bone calcium and phosphorus. Furthermore, trabecular bone loss in ovx was significantly suppressed by dietary xyl. These results indicate that a 10% dietary supplementation of xyl in ovx has a protective effect against the weakening of bone biomechanical properties. This is related to greater BV/TV and maintained bone mineral content.

Mattila PT, Svanberg MJ, Pökkä P, Knuuttila ML
J. Nutr. Oct 1998
PMID: 9772154 | Free Full Text