Production of 8-nitro-cGMP in osteocytic cells and its upregulation by parathyroid hormone and prostaglandin E2.

Osteocytes regulate bone remodeling, especially in response to mechanical loading and unloading of bone, with nitric oxide reported to play an important role in that process. In the present study, we found that 8-nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP), a second messenger of nitric oxide in various types of cells, was produced by osteocytes in bone tissue as well as cultured osteocytic Ocy454 cells. The amount of 8-nitro-cGMP in Ocy454 cells increased during incubation with parathyroid hormone or prostaglandin E2, both of which are known to upregulate receptor activator of nuclear factor-κB ligand (RANKL) mRNA expression in osteocytes. On the other hand, exogenous 8-nitro-cGMP did not have effects on either the presence or absence of these bioactive substances. Furthermore, neither an inhibitor of nitric oxide synthase nor 8-bromo-cGMP, a cell-permeable analog of cGMP, showed remarkable effects on mRNA expression of sclerostin or RANKL. These results indicate that neither nitric oxide nor its downstream compounds, including 8-nitro-cGMP, alone are sufficient for induction of functional changes in osteocytes.

The Criteria of Thickened Liquid for Dysphagia Management in Japan.

In Japan, the viscosity of thickened liquids is different among hospitals and nursing homes. In order to standardize viscosity of thickened liquids, the dysphagia diet committee of the Japanese Society of Dysphagia Rehabilitation developed the Japanese Dysphagia Diet 2013 (JDD2013). To decide on a definition of thickened liquids, the committee reviewed categories from other countries. Especially, the criteria of the USA and Australia were used as references. The definition had three levels: mildly thick, moderately thick, and extremely thick. Then a sensory evaluation by health care workers was carried out to decide the viscosity range of each level, and a draft document was made. After collecting public comments, follow-up experiments using thickened water with thickeners using xanthan gum were performed, and the JDD2013 (Thickened Liquid) was determined. The JDD2013 (Thickened Liquid) evaluated the drinking properties, visual properties, and viscosity values of each level. The shear rate of 50 s-1 was adopted to measure the viscosity with a cone and plate type viscometer to duplicate the measurement criteria used by the USA. We also set the values of the JDD2013 with the Line Spread Test to promote the use of guidelines in clinical practice. We believe the JDD2013 standards help hospitals and other settings that care for people with dysphagia to use the same thickness level and the same labels. In the future, the JDD2013 levels will be compared with new international guidelines to help with international understanding of the JDD2013 levels.

Nanoindentation time-dependent deformation/recovery suggestive of methylglyoxal induced glycation in calcified nodules.

Although empirical findings have indicated increase in bone fracture risk in type 2 diabetes patients, that has yet to be proven by results obtained at the material level. Here, we report evidence showing nanoscale time-dependent deformation/recovery of in vitro calcified nodules mimicking bone turnover in type 2 diabetes in respect to methylglyoxal (MG)-induced glycation. Nanoindentation test results revealed that calcified nodules cultured with MG did not show adequate dimensional recovery, despite a large creep rate during constant load indentation testing. This lesser recovery is likely based on the linear matrix polymerization network formed by advanced glycation end products (AGEs) as a secondary product of MG. Since elevated serum MG and abnormal bone turnover related to the amount of AGEs are observed in cases of type 2 diabetes, this time-dependent behavior may be one of the factors of the bone fracture mechanism at the material level in affected patients.

Effects of antibody to receptor activator of nuclear factor κ-B ligand on inflammation and cartilage degradation in collagen antibody-induced arthritis in mice.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory disease that leads to destruction of both articular cartilage and bone tissues. In rheumatic joints, synoviocytes and T-lymphocytes as well as bone cells produce the receptor activator of nuclear factor κ-B (RANK) ligand (RANKL), which binds to RANK on the surface of osteoclasts and their precursor cells to induce differentiation and activation of osteoclasts. Hence, inhibition of RANKL may be a promising approach to suppress osteolysis in RA. On the other hand, RANKL production by lymphocytes indicates the possibility that its inhibition would be effective to suppress inflammation in RA. In addition, it has been reported that cathepsin K, a predominant cysteine protease in osteoclasts, is involved in cartilage destruction in RA model mice. Here, we evaluated the effects of an anti-RANKL antibody on inflammation in footpads and degradation of articular cartilage in RA model mice. RESULTS: We induced arthritis in mice by injection of anti-type II collagen antibodies and lipopolysaccharide (LPS). Inhibition of RANKL by an anti-RANKL antibody (OYC1, Oriental Yeast, Tokyo, Japan) was confirmed by increased bone volume in the metaphysis of tibias. Swelling in either limb until day 14 was seen in 5 of 6 mice injected with anti-collagen antibodies and LPS without treatment with OYC1, while that was seen in 4 of 5 mice treated with OYC1. The average arthritis scores on day 14 in those groups were 2.17 and 3.00, respectively, indicating that OYC1 did not ameliorate inflammation in the limbs. Histological analyses indicated that OYC1 does not protect articular cartilage from destruction in mice with arthritis. CONCLUSIONS: Our present study failed to show the effectiveness of an anti-RANKL antibody to ameliorate inflammation in the limbs or protect articular cartilage from degradation in a collagen antibody-induced arthritis mouse model.