Cathepsin K Deficiency Suppresses Disuse-Induced Bone Loss.

Unloading induces bone loss and causes disuse osteoporosis. However, the mechanism underlying disuse osteoporosis is still incompletely understood. Here, we examined the effects of cathepsin K (CatK) deficiency on disuse osteoporosis induced by using sciatic neurectomy (Nx) model. After 4 weeks of surgery, CatK KO and WT mice were sacrificed and subjected to analyses. For cancellous bone rich region, Nx reduced the bone mineral density (BMD) compared to the BMD in the sham operated side in wild type mice. In contrast, CatK deficiency suppressed such Nx-induced reduction of BMD in cancellous bone. Nx also reduced BMD in the mid shaft cortical bone compared to the BMD in the corresponding region on the sham operated side in wild type mice. In contrast, CatK deficiency suppressed such Nx-induced reduction of BMD in the mid shaft cortical bone. Bone volume (BV/TV) was reduced by Nx in WT mice. In contrast, Cat-K deficiency suppressed such reduction in bone volume. Interestingly, CatK deficiency suppressed osteoclast number and osteoclast surface in the Nx side compared to sham side. When bone marrow cells obtained from Nx side femur of CatK-KO mice were cultured, the levels of the calcified area in culture were increased. Further examination of gene expression indicated that Nx suppressed the expression of genes encoding osteoblast-phenotype-related molecules such as Runx2 and alkaline phosphatase in WT mice. In contrast, CatK deficiency suppressed such reduction. These data indicate that CatK is involved in the disuse-induced bone mass reduction.

Frontal dysfunctions of ALS-PBP patients in relation to their bulbar symptoms and rCBF decline.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive and fatal disease characterized by progressive degeneration of spinal and bulbar motor neurons. However up to 50% ALS patients may also have cognitive dysfunction which has not been fully examined. METHODS: 35 ALS patients [23 patients presenting with limb-type ALS (ALS-limb) and 12 patients presenting with primary bulbar palsy (PBP)-type ALS (ALS-PBP)] and 5 Spinal and Bulbar Muscular Atrophy (SBMA) patients have participated. To assess cognitive function mini-mental state examination (MMSE), Hasegawa dementia scale-revised (HDS-R), and frontal assessment battery (FAB) were performed. Additionally the time to complete card flipping with a computerized touch panel-type screening test was also examined. To investigate regional cerebral blood flow (rCBF), single-photon emission computed tomography (SPECT) using a (99m)Tc labeled ethyl cysteinate dimer ((99m)Tc-ECD) were performed. Statistical image analysis was performed using the easy Z-score imaging system (eZIS). RESULTS: HDS-R and FAB scores were significantly lower in the ALS-PBP group than in age- and gender-matched control subjects or ALS-limb groups (p<0.01). The time to complete card flipping was significantly longer in the ALS-PBP group than in the control and ALS-limb groups (p<0.01). Although MMSE, HDS-R and FAB scores and the time to complete card flipping had no correlation with ALS functional rating scale-revised (ALSFRS-R) or Norris-limb scale scores, FAB score (r=0.63, p <0.01) and the time to complete card flipping (r=-0.66, p<0.01) were strongly correlated with Norris-bulbar score. The eZIS showed that rCBF of the frontal lobe was more severely declined in ALS-PBP patients than in ALS-limb patients (p<0.05). CONCLUSION: These results suggest a selective decline of frontal cerebral functions in the ALS-PBP group in relation to their bulbar symptoms and rCBF decline.

Monochromatic synchrotron radiation muCT reveals disuse-mediated canal network rarefaction in cortical bone of growing rat tibiae.

The purpose of this study was to demonstrate the ability of computed microtomography based on monochromatic synchrotron radiation (SRmuCT) in microstructural analysis of cortical bone. Tibial diaphyses of growing rats (14 wk, n = 8) undergoing unilateral sciatic neurectomy 8 wk before study were imaged with spatial volume resolution of 5.83 x 5.83 x 5.83 microm3 by SRmuCT (20 keV) at the synchrotron radiation facility (SPring-8). Reconstructed image data were translated into local mineral densities by using a calibrated linear relationship between linear absorption coefficients and concentrations of homogeneous K2HPO4 solution. Pure bone three-dimensional images, produced by simple thresholding at a bone mineral density of 0.82 g/cm3, were analyzed for macro- and microscopic structural properties. In neurectomized hindlimbs, cortical canal network rarefaction as well as bone atrophy were found. The former was characterized by 30% smaller porosity, 11% smaller canal density in transverse section, and 38% smaller canal connectivity density than those in contralateral bone. On the other hand, no difference was found in bone mineral density between neurectomized and intact hindlimbs (1.37 vs. 1.36 g/cm3). In conclusion, SRmuCT is a promising method for the three-dimensional analysis of cortical microstructure and the degree of mineralization in small animals.

Unilateral fibroadipose degeneration of the masticatory muscles.

A unique case of fatty replacement of the masticatory muscles, causing progressive limitation of mouth opening, is presented. Both CT and MRI revealed an almost total substitution of the masticatory muscles with fatty tissue, confirmed by the histopathology at surgery. Myotomy of masseter and internal pterygoid muscles and coronoidotomy improved his symptoms. There is no known cause of fibroadipose replacement of muscle fibres.