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Biomedical subjects

W S Jee

Publications and source records attributed to W S Jee.

At least 181 records · Page 10Linked to original sources

Effects of phytohemagglutinin-P (PHA-P) on bone of the growing rat.

The effects of phytohemagglutinin-P, (PHA-P), a mitogen known to selectively stimulate cells of hematogenous or lymphoid monocytic origin, 25 and 50 mg/kg/day administered for 15 days on proximal tibiae of growing male Sprague-Dawley rats, were studied. The general effect of PHA-P was to decrease the amount of cartilage, hard tissue, and longitudinal growth in the proximal tibial metaphysis. A decrease in longitudinal bone growth, in the number of chondrocytes, in the thickness of cartilage plate, in the metaphyseal mass of hard tissue, in the percentage of calcified cartilage core, and in the number of osteoblasts per mm of bone surface was observed. Additionally, PHA-P increased the number of osteoclasts, the number of labeled osteoclastic nuclei, and the average number of nuclei per osteoclast. There was a significant decrease in the time to the first appearance of labeled osteoclastic nuclei as the dose of PHA-P increased. Thus, PHA-P treatment leads to the dominance of osteoclastic over chondroblastic and osteoblastic activity and results in a hard tissue deficit in a growing skeleton. The data indicate that PHA-P administration selectively increases osteoclast numbers by elevating osteoclastic progenitor cell proliferation and enhancing their fusion and differentiation to osteoclasts.

Animals↗

1,25-Dihydroxyvitamin D3: short- and long-term effects on bone and calcium metabolism in patients with postmenopausal osteoporosis.

We evaluated the effects of therapy with a small dose (0.5 microgram/day) of 1,25-dihydroxyvitamin D3 in 12 previously untreated patients with postmenopausal osteoporosis. Combined radiocalcium kinetic and balance studies showed that at base line, net calcium absorption (mean +/- SEM) was low (7 +/- 3%), calcium balance was negative (-59 +/- 22 mg/day), and bone resorption rate (297 +/- 40 mg/day) exceeded bone formation rate (239 +/- 36 mg/day). After short-term therapy (6-8 months), calcium absorption was normal (27 +/- 3%, P less than 0.001 for difference from base line), calcium balance had improved (+2 +/- 26 mg/day, P less than 0.05), and bone resorption rate (195 +/- 35 mg/day, P less than 0.01) had decreased more than bone formation rate (197 +/- 26 mg/day, NS). Compared with base-line values, after long-term therapy (2 years) the increased level of calcium absorption was maintained (27 +/- 3%, P less than 0.001), but calcium retention declined to a level intermediate (-27 +/- 24 mg/day, NS) between base-line and short-term treatment values, and both bone resorption rate (294 +/- 33 mg/day, NS) and bone formation rate (267 +/- 34 mg/day, NS) increased. Urinary hydroxyproline excretion was lower than before treatment (26.3 +/-2.0 mg/day) after both short-term (21.1 +/- 1.6 mg/day, P less than 0.001) and long-term (22.0 +/- 1.8 mg/day, P less than 0.01) treatments. Trabecular bone volume was 11.3 +/- 1.0% at base line and increased to 16.0 +/- 1.2% (P less than 0.01) after long-term treatment. By contrast, the eight patients studied before and after 6-8 months of placebo treatment had no significant change in any variable.

Bone and Bones↗

Excessive mineralization with growth plate closure in rats on chronic warfarin treatment.

Rats maintained for 8 months on a level of warfarin sufficient to decrease the vitamin K-dependent protein of bone (bone Gla protein) to 2% of normal have an excessive mineralization disorder characterized by complete fusion of the proximal tibial growth plate and cessation of longitudinal growth. The general features of this abnormality resemble the fetal warfarin syndrome in humans, a disorder also characterized by excessive mineralization of the growth plate. These excessive mineralization disorders may be caused by the decreased levels of bone Gla protein, a protein that potently inhibits mineralization in vitro.

Animals↗

Bone loss in the beagle tibia: influence of age, weight, and sex.

In a cross-sectional study, 154 Beagles (79 males, 74 females) ranging in age from 14 to 187 months were measured for bone mineral, bone width, and mineral-to-width ratio on the distal shaft of the right tibia using a photon absorptiometer. The measurements were evaluated with regard to age, sex and body weight. The results indicate that males were heavier than females in body weight, with weight being reduced in the older animals of both sexes. When compared on an age basis, males had more mineral, a wider tibia, and a greater mineral-to-width ratio than females. The males and females reach their peak mineral, and mineral-to-width ratio at about 6 years of age and then decline. On a body weight basis, mineral, width and mineral-to-width ratio all increase with increasing body weight, with bone width being the least affected by changes in body weight. The values for females are less than those for males in all parameters with the greatest differences occurring at the greater weights. The only variance from these observations was the greater mineral-to-width ratio in the lighter females. It is concluded that, when examining cortical bone, the Beagle is a model of age-related osteopenia, and body weight is an important consideration when explaining changes in bone mineral.

Aging↗

Variations in mineral apposition rate of trabecular bone within the beagle skeleton.

The mineral apposition rate of trabecular bone was determined in several skeletal sites of young adult beagles. Tetracycline derivatives were administered intravenously or orally on 2 separate occasions preceding the day of sacrifice in order to label actively mineralizing bone surfaces. The rate of mineral apposition was calculated by dividing the distance between the 2 tetracycline markers by the time interval between their administration. The lumbar vertebra, proximal humerus, and pelvis, each of which contains red marrow, were found to have a significantly higher (P less than 0.001) rate of mineral apposition in trabecular bone than the skeletal sites containing yellow marrow--the proximal ulna and distal humerus. The mean apposition rate in the former 3 sites was 1.3 +/- 0.3 micrometers/day, while that in the latter 2 was 0.9 +/- 0.2 micrometers/day (uncorrected for plane of sectioning). It is tempting to speculate that this finding may be a consequence of differences in vascularity between red and yellow marrow.

Animals↗

Skeletal alterations in rats during space flight.

Male Wistar rats were placed in orbit for an 18.5 day period aboard the Soviet Cosmos 1129 biological satellite. The skeletal changes which occurred during space flight were a reduced rate of periosteal bone formation in the tibial and humeral diaphyses, a decreased trabecular bone volume, and an increased fat content of the bone marrow in the proximal tibial metaphysis.

Animals↗

Effect of dichloromethane diphosphonate on cortisol-induced bone loss in young adult rabbits.

Cortisol, 2.5 mg/kg, dichloromethane diphosphonate (Cl2MDP), 0.1, 1.0 and 4.0 mg/kg, and combinations of the two were administered daily for 42 days to young adult rabbits (3.9 kg) to determine if Cl2MDP could inhibit development of cortisol-induced osteopenia. A beginning and a terminal control group were included in the experiment. In the terminal controls compared with the beginning controls, the proximal tibia lost cortical and trabecular bone, the distal femur gained cortical bone and the lumbar vertebral body lost trabecular bone. The administration of Cl2MDP alone inhibited bone resorption at those sites where bone loss was occurring. Two cortical bone sites showed gains in bone. The 1.0 mg/kg dose was most effective. In rabbits administered cortisol, bone formation was inhibited; the number of osteoclasts was markedly increased, cortical bone was lost in all the bones examined, and there was no marked effect on trabecular bone. Cl2MDP administered with cortisol partially inhibited cortisol-induced bone loss. The concomitant administration of Cl2MDP did not alter the number of osteoclasts and osteoblasts. The 1.0 mg/kg dose was most effective. The results of this study clearly demonstrated the need to evaluate several bones and different sites within individual bones if erroneous conclusions are to be avoided when studying agents that affect bone metabolism.

Aging↗

Characterization of endosteal bone-lining cells from fatty marrow bone sites in adult beagles.

Bone-lining cells cover the majority of trabecular bone surfaces in adult long-lived mammals. The morphology, ultrastructure, and population density of bone-lining cells was investigated in several fatty marrow trabecular bone sites in adult beagles of different ages. Although there is a low population density of bone-lining cells on bone surfaces, their total numbers greatly exceed the numbers of osteoblasts and osteoclasts found on these bone surfaces. In one of the bone sites studied, there are significantly fewer bone-lining cells in very old beagles (12-16 years old) when compared to young adult beagles (1.5-3 years old), otherwise there are no differences in the cell population that could be attributed to aging. Bone-lining cells are flattened against bone surfaces and have flat or sometimes ovoid-shaped nuclei which are often located adjacent to areas in the fatty marrow where capillaries are found. When viewed in the electron microscope, bone-lining cells contain few organelles, and the attenuated cytoplasm of these cells is well extended over bone surfaces. The bone-lining cell cytoplasm does not appear to form a continuous layer over the bone surface, as numerous gaps and spaces are seen. Bone-lining cell processes are frequently joined by junctions morphologically similar to gap junctions. Between the lamina limitans of the bone matrix and the bone-lining cell, as well as between the bone-lining cell and the adjacent fat cells, there are layers of connective tissue containing collagenous fibers and other amorphous material. These findings are discussed in relation to the possible role of bone-lining cells in the regulation of mineral homeostasis.

Aging↗

A quantitative histologic analysis of the growing long bone metaphysis.

The purpose of this work was to analyze the proximal tibial metaphysis of the 170 g rat in a quantitative histologic fashion which would allow some relation to tissue age to be established. Stained 3 micrometers thick tissue sections were analyzed with the aid of a Merz grid on an eyepiece reticule and a light microscope. Tissue mass and cell distribution were studied in all areas. The rate of change in tissue mass during aging of the metaphysis was calculated. Two regions of the metaphysis were identified. One, corresponding to the primary spongiosa, less than 4.45 days of age, is a region of high turnover of hard tissue and high numbers of osteoblasts and osteoprogenitor cells. The other, corresponding to the secondary spongiosa, is a region of relatively low net tissue turnover and low numbers of osteoblasts and osteoprogenitor cells. Osteoclasts were found relatively more uniformly distributed through the metaphysis than were osteoblasts and osteoprogenitor cells. The rate of bone formation in the primary spongiosa is 50 times that found in the Haversian bone of the rib of 5-year-old humans and about 500 times that found at the cortical-endosteal surface of ribs of 5-year-old humans. It is argued that both cell distribution and tissue distribution in the metaphysis support the concept that osteoblasts and osteoclasts, rather than osteocytes, are responsible for the maturation of the metaphysis. The inhomogeneous distribution of both cells and tissue in the metaphysis has definite meaning for the interpretation of findings concerning the incorporation of radionuclides into the skeleton.

Aging↗

Bone cell kinetics during longitudinal bone growth in the rat.

The purpose of this work was to provide futher knowledge about bone cell kinetics in the metaphysis of the growing long bone. Seventy rats were sacrificed from 1 to 120 h after injection of tritiated thymidine. Autoradiographs of 3 micrometers thick sections of the proximal tibial metaphysis were studied in a manner which allowed evaluation of labeled cell nuclei as a function of increasing age of metaphyseal tissue. A cell cycle duration study for osteoprogenitor cells was done. Labeled osteoprogenitor cells and osteoblasts first appeared at 1 h post-injection. The great majority of all labeled osteoprogenitor cells and osteoblasts was found within 1 mm of the growth cartilage-metaphyseal junction (GCMJ) at all times, apparently migrating with the moving GCMJ. In contrast, labeled osteoclast nuclei first appeared at 24 h post-injection within 0.3 mm of the GCMJ and remained always with the area of bone surface with which they were first associated, even as the GCMJ migrated away. By 5 days post-injection, the source of new labeled osteoclast nuclei in the metaphysis near the GCMJ was depleted, whereas that for the osteoblasts remained. The existence of two kinetically different, as well as ultrastructurally different, members of the metaphyseal osteoprogenitor cells population is postulated. A cell cycle time of 39 +/- 18 h was found for the osteoprogenitor cell population, but has limited meaning. A schema for metaphyseal bone cell movements during longitudinal bone growth is presented.

Aging↗

The effect of dichloromethylene diphosphonate, a pyrophosphate analog, on bone and bone cell structure in the growing rat.

Dichloromethylene diphosphonate (Cl2MDP) is a synthetic compound related in structure to inorganic pyrophosphate but is resistant to enzymatic and chemical degradation and is known to be a potent inhibitor of bone resorption. The administration of 20 mg/kg/day of Cl2MDP for ten days to growing rats results in marked increases in metaphyseal mineralized tissue mass due to slowed bone resorption. There was an increase in resorption areas covering anorganic bone viewed by scanning electron microscopy (SEM), however, the resorption pits, or Howship's lacunae, in these resorption areas were smaller and less defined than those encountered in controls. The appearance of these large areas of poorly delineated resorption pits is likely due to an inhibition of bone resorption coupled with slow bone formation. Administration of Cl2MDP to growing rats also results in an increase in the numbers and size of osteoclasts. Because this would appear to be a histological paradox, in view of the ability of Cl2MDP to slow bone resorption, the osteoclasts were examined by transmission electron microscopy (TEM). The ruffled borders and associated cytoplasmic vacuoles were generally less extensive in the Cl2MDP-treated osteoclasts than in controls, even though clear zones were frequently seen. Examination of undecalcified light microscope sections reveal that the area of bone being degraded by adjacent osteoclasts was generally much smaller in the Cl2MDP-treated animals than in controls. Thus the collaborating TEM observations of smaller ruffled borders, with the SEM observations of smaller, less-defined resorption pits, with the light microscope observations of smaller bone areas being degraded by individual osteoclasts provide a morphological basis for the observed decreases in bone resorption following Cl2MDP administration.

Animals↗