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We compared the distribution of a cysteine proteinase inhibitor, cystatin C, with that of cathepsin K in osteoclasts of the mouse tibia by immunolight and immunoelectron microscopy. Light microscopically, strong immunoreactivity for cystatin C was found extracellularly along the resorption lacuna and intracellularly in the organelles of osteoclasts. In serial sections, various patterns of cystatin...
PvuII and XbaI restriction fragment length polymorphisms (RFLPs) for the estrogen receptor gene (ERG) and its relation to bone mineral density (BMD) were examined in 454 postmenopausal Chinese women, aged 55-79 years. The RFLPs were represented as P or p (PvuII) and X or x (XbaI), with capital letters signifying the absence of and small letters the presence of restriction sites. There was no significant...
Age-related osteopenia is known to occur differently throughout the skeleton. In the present study, we examine the influence of donor age (<50 and >50 years), and bone structure (cortical vs. trabecular) on osteocalcin and vitamin D receptor (VDR) expression in primary cultures of human osteoblastic cells (hOB) cells. Cells were isolated from trabecular bone samples obtained from donors undergoing...
Among the bone morphogenetic protein (BMP) family, which plays a crucial role not only in bone formation but also in development, BMP-2, -4, and -7 participate predominantly in various aspects. To undertake complex tasks, their expression is strictly controlled. In this study we isolated and analyzed the 5'-flanking regions of the human BMP-4 and -7 genes to elucidate the mechanism of their temporally...
Estrogen's action on bone may be mediated by cytokines produced by monocytes. We have reported a decreased ratio of interleukin-1β (IL-1β) to interleukin-1 receptor antagonist (IL-1ra) produced by whole blood cultures in vivo in women taking hormone replacement therapy (HRT). Also, one study has shown an effect of estradiol on tumor necrosis factor-α (TNF-α) secretion by separated monocytes in vitro...
The exact mechanism of bone loss remains unknown in primary male osteoporosis. It has been suggested that estrogen and sex hormone binding globulin (SHBG) play a role in regulating bone turnover and bone mass in healthy men > 65 years of age. In the present study, 80 men (mean age 49.7 years) with bone mineral density >2.5 SD below the young adult value and 40 age-matched controls were recruited...
Although bone strength and modulus are known to be influenced by both volume fraction and mineral content (ash fraction), the relative influence of these two parameters remains unknown. Single-parameter power law functions are used widely to relate bone volume or ash fraction to bone strength and elastic modulus. In this study we evaluate the potential for predicting bone mechanical properties with...
Regulated intercellular signaling is essential for the maintenance of bone mass. In recent work we described how osteoblasts and osteoclasts express functional receptors for the excitatory amino acid, glutamate, indicating that a signaling pathway analogous to synaptic neurotransmission exists in bone. Here, we show that osteoblasts also express the essential molecular framework for regulated glutamate...
Levormeloxifene, a nonsteroidal selective estrogen receptor modulator (SERM), has been evaluated for its effects on bone in cynomolgus monkeys (Macaca fascicularis). Adult female monkeys were imported from Indonesia and randomized into six groups of 25-28 animals each (n = 158). Animals in one group were sham ovariectomized (sham) and received vehicle. Animals in the remaining five groups were ovariectomized...
The aim of the study was to establish a relationship between mothers' and daughters' bone status. Forty-eight postmenopausal women and their 48 premenopausal daughters were evaluated. The analysis was made for the whole group and for two subgroups: 27 healthy mothers and their 27 daughters; and 21 fractured mothers and their 21 daughters. The subgroups were matched for age and years since menopause...
It is well recognized that high-dose estrogen induces a marked osteogenic response in long bones of female mice. In light of evidence which suggests that nitric oxide synthase (NOS) plays a role in regulation of osteoblast activity, we analyzed whether NOS is involved in mediating this response. Intact female mice were administered 17β-estradiol (E 2 ) either alone or in combination with N...
Salmon calcitonin (sCT) is widely used therapeutically in the treatment of patients with postmenopausal osteoporosis, Paget's disease, and some forms of hypercalcemia. Preparations of synthetic calcitonin peptides of high purity and reproducibility are now routinely produced and physicochemical methods, particularly reverse-phase high-performance liquid chromatography (RP-HPLC), are replacing the...
In the last decade, an increased frequency of fractures among wild moose in the southernmost parts of Norway has been reported. This study focuses on bone mass, mechanical strength, and metal levels in the metacarpal bone of moose hunted in Aust-Agder (AA) County in southern Norway compared with control areas (CA) in more eastern and northern parts. Metacarpal bone with soft tissue from 106 AA and...
This study documents growth and dual-energy X-ray absorptiometry (DXA)-determined peak bone mass profiles in the rabbit model, and tests the hypothesis that rabbits show patterns of bone accretion similar to humans and thus may serve as a viable model for human bone physiology. It is also shown that dietary Ca intake affects peak bone mass and the temporal pattern of its attainment. Groups of weaned...
Osteoporosis is a common occurrence in aging men. There is currently no appropriate animal model for studying age-related bone loss in men. To determine whether male Sprague-Dawley (SD) rats experience bone loss with aging and whether this rodent model is appropriate for studying age-related bone loss in men, SD rats aged 1-27 months were examined at the L-4 vertebra, the left femoral neck, and the...
Amylin and calcitonin gene-related peptide (CGRP) are homologous 37 amino acid peptides that are found in the circulation. Both peptides belong to the calcitonin family. Similar to calcitonin, amylin and CGRP inhibit osteoclast activity, although they are much less potent than calcitonin. Calcitonin is known to act on the latter stages of osteoclast development, inhibiting the fusion of committed...
Appositional and longitudinal growth of long bones are influenced by mechanical stimuli. Using the noninvasive rat ulna loading model, we tested the hypothesis that brief-duration (10 min/day) static loads have an inhibitory effect on appositional bone formation in the middiaphysis of growing rat ulnae. Several reports have shown that ulnar loading, when applied to growing rats, results in suppressed...
A previous report of elevated dual-energy X-ray absorptiometry (DXA) bone mineral density (BMD) Z scores suggests that Hutterite females might be significantly less likely to develop osteoporosis compared with other U.S. females. In the present study, we sought to determine if high Hutterite DXA BMD Z scores were elevated because of larger bone size. Hutterites reside in isolated, self-sufficient...
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