Kin-ya Kubo

Age-Related Changes in Trabecular and Cortical Bone Microstructure

The elderly population has substantially increased worldwide. Aging is a complex process, and the effects of aging are myriad and insidious, leading to progressive deterioration of various organs, including the skeleton. Age-related bone loss and resultant osteoporosis in the elderly population increase the risk for fractures and morbidity. Osteoporosis is one of the most common conditions associated with aging, and age is an independent risk factor for osteoporotic fractures. With the development of noninvasive imaging techniques such as computed tomography (CT), micro-CT, and high resolution peripheral quantitative CT (HR-pQCT), imaging of the bone architecture provides important information about age-related changes in bone microstructure and estimates of bone strength. In the past two decades, studies of human specimens using imaging techniques have revealed decreased bone strength in older adults compared with younger adults. The present paper addresses recently studied age-related changes in trabecular and cortical bone microstructure based primarily on HR-pQCT and micro-CT. We specifically focus on the three-dimensional microstructure of the vertebrae, femoral neck, and distal radius, which are common osteoporotic fracture sites.

Occlusal disharmony induces spatial memory impairment and hippocampal neuron degeneration via stress in SAMP8 mice

We examined the effect of occlusal disharmony in senescence-accelerated (SAMP8) mice on plasma corticosterone levels, hippocampal neuron number, and spatial performance in the water maze. The bite-raised condition was associated with an accelerated age-related decline in spatial memory, increased plasma corticosterone levels, and a decreased number of neurons in the hippocampal CA3 region. The findings suggest that the bite-raised condition in aged SAMP8 mice induces hippocampal neuron loss, thereby leading to senile memory deficits.

Molarless-induced changes of spines in hippocampal region of SAMP8 mice.

We examined the effect of the molarless condition on the dendritic spines of hippocampal pyramidal cells in SAMP8 mice in comparison to its effect on learning ability in a maze test. The molarless condition caused a decrease in the number of the spines of CA1 pyramidal cells only in the aged mice showing a reduced learning ability. The results suggest the involvement of the molarless condition in an attenuation of input activities in the hippocampal synapses.

Effects of Mandibular Deviation on Brain Activation During Clenching: An fMRI Preliminary Study

Abstract Using functional magnetic resonance imaging (fMRI) in eight healthy human subjects, the present study measured blood oxygenation level-dependent (BOLD) signals during clenching in a malocclusion model, using a custom-made splint that forced the mandible to a retrusive position and a splint of no modification for control, and compared the results to the BOLD signals during the corresponding resting conditions. An individual visual analog scale (VAS) score was also examined during clenching to evaluate the interactions between fMRI data and psychiatric changes. During both clenchings, activations in four brain regions (premotor cortex, prefrontal cortex, sensorimotor cortex, and insula) were seen. However, clenching in the malocclusion model, with psychological discomfort, increased additionally BOLD signals in the anterior cingulate cortex and the amygdala. Furthermore, there was a parallel relationship between BOLD signal intensities and VAS scores in these two regions. The findings may suggest the involvement of clenching with malocclusal conditions in the emotion and/or pain-related neural processing in the brain.

Occlusal disharmony attenuates glucocorticoid negative feedback in aged SAMP8 mice.

To evaluate the mechanism underlying impaired cognitive function due to occlusal disharmony, we examined the effect of the bite-raised condition on spatial performance and hippocampal expression of glucocorticoid receptors (GR) and glucocorticoid receptor messenger ribonucleic acid (GRmRNA) using behavioral, immunohistochemical, and in situ hybridization techniques. Learning ability in the water maze test was significantly impaired in aged bite-raised mice compared with age-matched control mice. There was no difference between control and bite-raised young and middle-aged mice. Also, immunohistochemical and in situ hybridization analysis showed that the bite-raised condition enhanced the age-related decrease in GR and GRmRNA expression in the hippocampus. In particular, GR and GRmRNA expressions were significantly decreased in aged bite-raised mice compared to age-matched control mice. These findings suggest that the bite-raised condition in aged SAMP8 mice decreases GR and GRmRNA, which impairs the hypothalamic-pituitary-adrenal feedback inhibition, thereby leading to memory deficits.

Chewing Maintains Hippocampus-Dependent Cognitive Function

Mastication (chewing) is important not only for food intake, but also for preserving and promoting the general health. Recent studies have showed that mastication helps to maintain cognitive functions in the hippocampus, a central nervous system region vital for spatial memory and learning. The purpose of this paper is to review the recent progress of the association between mastication and the hippocampus-dependent cognitive function. There are multiple neural circuits connecting the masticatory organs and the hippocampus. Both animal and human studies indicated that cognitive functioning is influenced by mastication. Masticatory dysfunction is associated with the hippocampal morphological impairments and the hippocampus-dependent spatial memory deficits, especially in elderly. Mastication is an effective behavior for maintaining the hippocampus-dependent cognitive performance, which deteriorates with aging. Therefore, chewing may represent a useful approach in preserving and promoting the hippocampus-dependent cognitive function in older people. We also discussed several possible mechanisms involved in the interaction between mastication and the hippocampal neurogenesis and the future directions for this unique fascinating research.

The osteocyte plays multiple roles in bone remodeling and mineral homeostasis

Osteocytes are the most abundant cells in bone and are the major orchestrators of bone remodeling and mineral homeostasis. They possess a specialized cellular morphology and a unique molecular feature. Osteocytes are a stellate shape with numerous long, slender dendritic processes. The osteocyte cell body resides in the bone matrix of the lacuna and the dendritic processes extend within the canaliculi to adjacent osteocytes and other cells on the bone surface. Osteocytes form extensive intercellular network to sense and respond to environmental mechanical stimulus by the lacunar–canalicular system and gap junction. Osteocytes are long-lived bone cells. They can undergo apoptosis, which may have specific regulatory effects on osteoclastic bone resorption. Osteocytes can secrete several molecules, including sclerostin, receptor activator of nuclear factor κB ligand and fibroblast growth factor 23 to regulate osteoblastic bone formation, osteoclastic bone resorption and mineral homeostasis. A deeper understanding of the complex mechanisms that mediate the control of osteoblast and osteoclast function by osteocytes may identify new osteocyte-derived molecules as potential pharmacological targets for treating osteoporosis and other skeletal diseases.

Bone three-dimensional microstructural features of the common osteoporotic fracture sites

Osteoporosis is a common metabolic skeletal disorder characterized by decreased bone mass and deteriorated bone structure, leading to increased susceptibility to fractures. With aging population, osteoporotic fractures are of global health and socioeconomic importance. The three-dimensional microstructural information of the common osteoporosis-related fracture sites, including vertebra, femoral neck and distal radius, is a key for fully understanding osteoporosis pathogenesis and predicting the fracture risk. Low vertebral bone mineral density (BMD) is correlated with increased fracture of the spine. Vertebral BMD decreases from cervical to lumbar spine, with the lowest BMD at the third lumbar vertebra. Trabecular bone mass of the vertebrae is much lower than that of the peripheral bone. Cancellous bone of the vertebral body has a complex heterogeneous three-dimensional microstructure, with lower bone volume in the central and anterior superior regions. Trabecular bone quality is a key element to maintain the vertebral strength. The increased fragility of osteoporotic femoral neck is attributed to low cancellous bone volume and high compact porosity. Compared with age-matched controls, increased cortical porosity is observed at the femoral neck in osteoporotic fracture patients. Distal radius demonstrates spatial inhomogeneous characteristic in cortical microstructure. The medial region of the distal radius displays the highest cortical porosity compared with the lateral, anterior and posterior regions. Bone strength of the distal radius is mainly determined by cortical porosity, which deteriorates with advancing age.

Dynorphin-A immunoreactive terminals on the neuronal somata of rat mesencephalic trigeminal nucleus.

Dynorphin-A-like immunoreactivity was investigated in the rat mesencephalic trigeminal nucleus (Mes 5) at the light and electron microscopic levels. Dynorphin-A immunoreactive fibers and puncta, likely representing nerve terminals, were observed throughout rostrocaudal extension of the Mes 5 at the light microscopic level. Within the rostrocaudal extension, more abundant fibers and puncta were localized in the midbrain-pontine junction and pontine areas than in the midbrain area. At the electron microscopic level, dynorphin-A immunoreactive synapses were observed on the somata of Mes 5. Dynorphin-A-like immunoreactivity tended to be restricted to dense-cored vesicles in the synapses. These results suggest that dynorphin-A-containing fiber systems affect mastication through the Mes 5.

Combined treatment with a traditional Chinese medicine, Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) and alendronate improves bone microstructure in ovariectomized rats.

ETHNOPHARMACOLOGICAL RELEVANCE Hachimi-jio-gan is one of the most common recipes in traditional Chinese, Japanese and Korean medicines and has been used for preventing and treating various diseases associated with aging, including osteoporosis. AIM OF THE STUDY The present study was performed to examine the combined effects of a traditional Chinese medicine, Hachimi-jio-gan (HJG) and antiresorptive agent, alendronate (ALN) on ovariectomy-induced bone loss in rats. MATERIALS AND METHODS Six-month-old female Sprague-Dawley rats were underwent ovariectomy (OVX) or sham operation. Eight weeks later, the OVX rats were treated either with HJG or ALN alone or in combination of both. The skeletal response was evaluated using micro-computed tomography (micro-CT), image analysis software, and biochemical markers. RESULTS This study demonstrated that treatment with HJG or ALN alone increased trabecular bone volume and bone mineral density (BMD), and partially improved bone microstructure of the proximal tibia and vertebra in OVX rats. Treatment with ALN to OVX rats resulted in significant reduction in both bone resorption and bone formation. Treatment with HJG to OVX rats inhibited bone resorption, with no marked effects on bone formation. Combined treatment of HJG and ALN significantly improved trabecular bone mass and bone microstructure, compared with either agent alone. CONCLUSIONS We conclude that the combined treatment with HJG and ALN has beneficial effects on trabecular bone mass, improving the structural properties of both tibia and vertebra in OVX rats.