Decreased bone mineral density in experimental myasthenia gravis in C57BL/6 mice.

Experimental autoimmune myasthenia gravis (EAMG), an animal model of myasthenia gravis (MG), can be induced in C57BL/6 (B6, H-2 b) mice by 2-3 injections with Torpedo californica AChR (tAChR) in complete Freund's adjuvant. Some EAMG mice exhibit weight loss with muscle weakness. The loss in body weight, which is closely associated with bone structure, is particularly evident in EAMG mice with severe muscle weakness. However, the relationship between muscle weakness and bone loss in EAMG has not been studied before. Recent investigations on bone have shed light on association of bone health and immunological states. It is possible that muscle weakness in EAMG developed by anti-tAChR immune responses might accompany bone loss. We determined whether reduced muscle strength associates with decreased bone mineral density (BMD) in EAMG mice. EAMG was induced by two injections at 4-week interval of tAChR and adjuvants in two different age groups. The first tAChR injection was either at age 8 weeks or at 15 weeks. We measured BMD at three skeletal sites, including femur, tibia, and lumbar vertebrae, using dual energy X-ray absorptiometry. Among these bone areas, femur of EAMG mice in both age groups showed a significant decrease in BMD compared to control adjuvant-injected and to non-immunized mice. Reduction in BMD in induced EAMG at a later-age appears to parallel the severity of the disease. The results indicate that anti-tAChR autoimmune response alone can reduce bone density in EAMG mice. BMD reduction was also observed in adjuvant-injected mice in comparison to normal un-injected mice, suggesting that BMD decrease can occur even when muscle activity is normal. Decreased BMD observed in both tAChR-injected and adjuvant-injected mice groups were discussed in relation to innate immunity and bone-related immunology involving activated T cells and tumour necrosis factor-related cytokines that trigger osteoclastogenesis and bone loss.

Rod-shaped and substituted hydroxyapatite nanoparticles stimulating type 1 and 2 cytokine secretion.

A Th1 immune response is required for modern vaccines as the most commonly used alum adjuvant has weak capacity for inducing Th1 immune response. Herein, rod-shaped hydroxyapatite (HA), magnesium-substituted HA (MgHA) and zinc-substituted HA (ZnHA) nanoparticles with irregular nanopores were synthesized and used as immunoadjuvants. Magnesium and zinc substitution in HA showed no influence on morphology, particle size, zeta potential and surface area of the nanoparticles. The rod-shaped MgHA and ZnHA nanoparticles promoted the cellular uptake of a molecular immunopotentiator, stimulated both type 1 and 2 cytokine secretion in vitro that relate to Th1 and Th2 immunity of bone marrow dentritic cells, respectively. The MgHA and ZnHA nanoparticles may be useful as immunoadjuvants for human.

Long-term resveratrol treatment prevents ovariectomy-induced osteopenia in rats without hyperplastic effects on the uterus.

Resveratrol (Res), a polyphenol that is abundant in many medicinal plants and is a selective oestrogen receptor modulator, exhibits multiple biological activities. In the present study, we determined whether Res prevents oestrogen deficiency-induced osteopenia and whether Res administration decreases pathological changes in the endometrium and lumen of the uterus compared with oestradiol replacement therapy (ERT). A total of sixty 3-4-month-old female Wistar rats were randomly divided into a sham-operated group (Sham) and five ovariectomy (OVX) subgroups, i.e. OVX rats as a control group (OVX); OVX rats receiving oestradiol valerate (ERT, 0·8 mg/kg); and OVX rats receiving Res 20, 40 and 80 mg/kg. Daily oral administration was initiated at week 2 after OVX for 12 weeks. A dose-response difference was observed in the effects of Res on bone mineral density (BMD) and trabecular microarchitecture. Only at the highest dose, bone loss was almost equivalent to that observed in the ERT group. The dose-response effects of Res on the biochemical parameters (alkaline phosphatase, IL-6, TNF-α and transforming growth factor-ß1 concentrations in the serum as well as urinary Ca and P excretion) and the expressions of receptor activator of nuclear factor κB ligand (RANKL) and the RANKL:osteoprotegerin protein ratio in the femur were also observed. Furthermore, the thickening of the endometrium and the infiltration of lymphocytes were prevented in all the three Res-treated groups compared with the ERT group. In conclusion, Res treatment not only improves BMD and trabecular microarchitecture but also does not affect the uterus and Res might be a potential remedy for the treatment of postmenopausal osteoporosis.

Silicon deprivation does not significantly modify the acute white blood cell response but does modify tissue mineral distribution response to an endotoxin challenge.

An experiment with rats was conducted to determine whether silicon deprivation affects the acute-phase immune response to an endotoxin challenge. Weanling female rats were assigned to two weight-matched groups of 24; one group was fed a basal diet containing about 1.9 microg Si/kg; the other group was fed the basal diet supplemented with 35 microg Si/kg as arginine silicate inositol complex. After being fed their respective diets for 8 weeks, 12 rats in each group were injected subcutaneously with 1 mg lipopolysaccharide (LPS)/kg body weight; the other 12 rats in each group were injected with deionized water. Two hours after injection, the rats were anesthetized with ether for collection of blood (for plasma), liver and femurs, and then euthanized by decapitation. LPS injection decreased total white blood cell, lymphocyte, monocyte, eosinophil, and basophil counts by 80-90%, but did not affect neutrophil counts. LPS injection also increased plasma tumor necrosis factor-alpha and osteopontin and decreased plasma hyaluronic acid. Silicon deprivation did not significantly affect any of these responses to LPS. Silicon in liver and silicon, iron, and zinc in femur were increased by LPS injection only in silicon-deprived rats. Silicon deprivation also increased monocyte counts and osteopontin and decreased femur zinc in rats not injected with LPS. The findings indicate that silicon deprivation does not affect the acute-immune phase decrease in inflammatory cell numbers and increase in inflammatory cytokines in response to an endotoxin challenge. Silicon deprivation, however, apparently causes slight chronic inflammation and might influence inflammatory cell proliferation in the chronic-phase inflammatory response.