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At least 847 records · Page 47Linked to original sources
PubMed2000

Clonal analysis of NK cell development from bone marrow progenitors in vitro: orderly acquisition of receptor gene expression.

In the mouse, two families of MHC class I-specific receptors, namely Ly49 and CD94/NKG2, have been identified on NK cells. Individual NK cells can express several Ly49 molecules as well as members of the CD94/NKG2 family. The expression of multiple receptors with different specificities for MHC class I is thus thought to generate NK cells with diverse recognition patterns. To delineate the mechanism by which NK cells begin to express different patterns of Ly49 and CD94/NKG2 molecules, we developed a clonal assay in which NK1.1(-), IL-2/ IL-15 receptor beta+ NK precursors generated by culture of multipotential Lin(-), c-kit+ progenitors in IL-7, stem cell factor and flt3 ligand are induced to differentiate into NK1.1+ , Ly49+ NK cells. Examination of the clonal populations thus generated revealed heterogeneity in the pattern of Ly49 and CD94/NKG2 gene expression. In addition, a distinct kinetic pattern of expression was observed. CD94, NKG2A, NKG2C and Ly49B were expressed first followed by Ly49G, then Ly49C and I and finally, Ly49A, D, E and F. The data suggest a stochastic but ordered acquisition of class I receptors on NK cells in which developing NK cells become capable of expressing distinct receptors at different times but show no absolute prerequisite to express the receptors that are acquired early in NK development for the expression of those that are acquired later.

Animals↗
PubMed2003

Zoledronic acid treatment of 5T2MM-bearing mice inhibits the development of myeloma bone disease: evidence for decreased osteolysis, tumor burden and angiogenesis, and increased survival.

Multiple myeloma is characterized by the growth of plasma cells in the bone marrow and the development of osteolytic bone disease. Myeloma cells are found closely associated with bone, and targeting this environment may therefore affect both the bone disease and the growth of myeloma cells. We have investigated the effect of the potent bisphosphonate, zoledronic acid, on the development of bone disease, tumor burden, and disease-free survival in the 5T2MM model of myeloma. 5T2MM murine myeloma cells were injected intravenously into C57BL/KaLwRij mice. After 8 weeks, all animals had a paraprotein. Animals were treated with zoledronic acid (120 microg/kg, subcutaneously, twice weekly) or vehicle, from the time of tumor cell injection or from paraprotein detection for 12 or 4 weeks, respectively. All animals injected with tumor cells developed osteolytic lesions, a decrease in cancellous bone volume, an increase in osteoclast perimeter, and a decrease in bone mineral density. Zoledronic acid prevented the formation of lesions, prevented cancellous bone loss and loss of bone mineral density, and reduced osteoclast perimeter. Zoledronic acid also decreased paraprotein concentration, decreased tumor burden, and reduced angiogenesis. In separate experiments, Kaplan-Meier analysis demonstrated a significant increase in survival after treatment with zoledronic acid when compared with control (47 vs. 35 days). A single dose of zoledronic acid was also shown to be effective in preventing the development of osteolytic bone disease. These data show that zoledronic acid is able to prevent the development of osteolytic bone disease, decrease tumor burden in bone, and increase survival in a model of established myeloma.

Animals↗
PubMed1995

Hydroxyapatite-clay bone fixation for loaded implants.

A clay containing hydroxyapatite (HA clay), which was made by mixing HA granules (range of sizes: 0.1-0.3 mm) and a saline solution of sodium alginate, was inserted into the medullary canal of an osteotomized rabbit's tibia with a Ti-6Al-4V titanium alloy implant. Each implant had a conical portion for bearing load. The shear strength of the bone-implant interface for the implant with HA clay was significantly greater than that for the implant without HA clay 3 months postoperatively (P < .02), while there was no significant difference between the two strengths 1 week postoperatively. Under microscopic observation, the percentage of area of newly developed bone was also significantly greater for the implant with HA clay than for the implant without HA clay 3 months postoperatively (P < .04). This study suggests that HA clay encouraged adequate bone fixation of the loaded implant in 3 months, while the clay was not effective for immediate fixation.

Alloys↗
PubMed2000

Parathyroid hormone-related peptide and Indian hedgehog.

Normal endochondral bone development requires temporal and spatial coordination of various cell types. Parathyroid hormone-related peptide and Indian hedgehog interact with each other and form a feedback loop that plays a major role in this coordination. Defects in the signalling of either of the two molecules cause severe bone malformations.

Animals↗
PubMed2003

Deletion of the P2X7 nucleotide receptor reveals its regulatory roles in bone formation and resorption.

The P2X7 nucleotide receptor is an ATP-gated ion channel expressed widely in cells of hematopoietic origin. Our purpose was to explore the involvement of the P2X7 receptor in bone development and remodeling by characterizing the phenotype of mice genetically modified to disrupt the P2X7 receptor [knockout (KO)]. Femoral length did not differ between KO and wild-type (WT) littermates at 2 or 9 months of age, indicating that the P2X7 receptor does not regulate longitudinal bone growth. However, KO mice displayed significant reduction in total and cortical bone content and periosteal circumference in femurs, and reduced periosteal bone formation and increased trabecular bone resorption in tibias. Patch clamp recording confirmed expression of functional P2X7 receptors in osteoclasts from WT but not KO mice. Osteoclasts were present in vivo and formed in cultures of bone marrow from KO mice, indicating that this receptor is not essential for fusion of osteoclast precursors. Functional P2X7 receptors were also found in osteoblasts from WT but not KO mice, suggesting a direct role in bone formation. P2X7 receptor KO mice demonstrate a unique skeletal phenotype that involves deficient periosteal bone formation together with excessive trabecular bone resorption. Thus, the P2X7 receptor represents a novel therapeutic target for the management of skeletal disorders such as osteoporosis.

Animals↗
PubMed1986

Retinoic acid enhances and depresses in vitro development of cartilaginous bone anlagen in embryonic mouse limbs.

Forelimbs of Day 11 and Day 12 embryonic mice were excised and cultured for 3 d in the presence of either 0.25 microgram (8 X 10(-7) M), 0.5 microgram (1.7 X 10(-6) M), or 1.0 microgram (3.3 X 10(-6) M) of all-trans retinoic acid (RA) per milliliter of culture medium. Cultured limbs were fixed, stained, and mounted whole on glass slides and evaluated with computerized optical image analysis for RA-induced effects on the area and shape of the total limb and individual bone anlagen. Relative effects of RA on total bone, soft tissue, long bone, and paw regions were also examined. With Day 11 forelimbs total bone area was increased by 10.5% by the low dose of RA. The increase was mostly in long bones and at the expense of soft tissue. Total bone area was increased 9.3% with Day 12 forelimbs. This increase was primarily in the paw. The high dose of RA decreased Day 11 forelimb area, primarily affecting long bones. Day 12 forelimbs were not significantly affected by the high dose of RA. Effects of the intermediate dose were primarily limited to reduction in soft tissue area. Long bone:paw and soft tissue:bone ratios reflected these effects. The high dose produced a consistent rounding or shortening of Day 11 forelimb bones. On Day 12 0.5 microgram/ml RA produced an inconsistent pattern of rounding of bone anlagen. Treatment with the high dose on Day 12 produced angular rather than rounded contours in many cases, as indicated by shape factor values closer to zero than obtained with controls. These data show that direct exposure to RA can affect both the size and shape of bone anlagen of the developing limb; the low dose enhances and the high dose depresses development. The results support previous studies which suggest that RA may play a critical role in the control of cell activities such as cell migration, proliferation, and cytodifferentiation in the development of the cartilaginous bone anlagen.

Animals↗
PubMed1984

Bone metastases in primary operable breast cancer. The role of serial scintigraphy.

In 1978 and 1979, 1060 Danish patients with primary operable breast cancer were bone-scanned for osseous metastases before entering a nationwide therapeutical trial. A re-reading group interpreted the scans produced in 12 participating hospitals. As a consequence standardized guide-lines for interpretation were agreed upon from 1979. The frequency of positive bone scans suggesting bone metastases fell abruptly from 1978 to 1979, as read both locally and by the re-reading group. As measured statistically the difference between the interpretation of the local and the re-reading groups remained unchanged. Of the 1060 patients 760 were followed by repeated pre-scheduled scans 6 and 12 months after surgery until any kind of recurrence was diagnosed. Only 37 of the 760 patients (4.9%) developed bone metastases verified by radiology or autopsy during the first 2 yr after surgery. A single positive scan, especially performed 6 or 12 months after surgery, as well as two or three scans repeatedly staying or becoming positive increase significantly the risk of developing bone metastases within 12 months after the latest scan. In 13 of the 37 patients with otherwise subsequently proven bone metastases the latest scan(s) were negative. It is concluded that a fixed schedule of repeated bone scans in patients with breast cancer is not warranted.

Bone Neoplasms↗
PubMed2001

Osteoprotegerin inhibits the development of osteolytic bone disease in multiple myeloma.

Multiple myeloma is a B-cell malignancy characterized by the accumulation of plasma cells in the bone marrow and the development of osteolytic bone disease. The present study demonstrates that myeloma cells express the critical osteoclastogenic factor RANKL (the ligand for receptor activator of NF-kappa B). Injection of 5T2MM myeloma cells into C57BL/KaLwRij mice resulted in the development of bone disease characterized by a significant decrease in cancellous bone volume in the tibial and femoral metaphyses, an increase in osteoclast formation, and radiologic evidence of osteolytic bone lesions. Dual-energy x-ray absorptiometry demonstrated a decrease in bone mineral density (BMD) at each of these sites. Treatment of mice with established myeloma with recombinant osteoprotegerin (OPG) protein, the soluble decoy receptor for RANKL, prevented the development of lytic bone lesions. OPG treatment was associated with preservation of cancellous bone volume and inhibition of osteoclast formation. OPG also promoted an increase in femoral, tibial, and vertebral BMD. These data suggest that the RANKL/RANK/OPG system may play a critical role in the development of osteolytic bone disease in multiple myeloma and that targeting this system may have therapeutic potential.

Animals↗
PubMed2003

Expression of NG2 proteoglycan during endochondral and intramembranous ossification.

We have used immunohistochemistry to study the distribution of the NG2 proteoglycan during bone development in the mouse. At embryonic day 15.5, NG2 was strongly detected in the immature cartilage of developing limbs. After transient down-regulation in mature chondrocytes, NG2 was up-regulated during primary ossification, colocalizing with alkaline phosphatase and tenascin C. In the epiphyseal growth plates of newborn mouse tibia, NG2 and alkaline phosphatase exhibited overlapping patterns of expression by hypertrophic chondrocytes and by osteoblasts surrounding newly formed bone trabeculae. NG2 was down-regulated after puberty, being only faintly detectable in the tibial growth plates of 3-month-old mice. In cranial sutures, NG2 was strongly labeled in osteogenic bone fronts and in the suture matrix. Our results indicate that NG2 expression is up-regulated during both endochondral and intramembranous ossification, but is down-regulated as ossification is completed.

Alkaline Phosphatase↗
PubMed1997

Effect of enzyme replacement therapy on bone formation in a feline model of mucopolysaccharidosis type VI.

A range of skeletal abnormalities are evident in mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome) including short stature and dysostosis multiplex, resulting from a deficiency in the lysosomal hydrolase N-acetylgalactosamine-4-sulphatase (4S). In this article, bone pathology was assessed in a feline model of MPS VI to evaluate the efficacy of enzyme replacement therapy (ERT) as a treatment modality for this genetic disorder. Osteopenia is clearly evident in MPS VI animals, with bone mineral volume (BV/TV) falling well below that of normal animals (4.39% vs. 20.11%, respectively). Trabecular bone architecture was also affected in MPS VI with fewer, thinner, and more widely spaced trabeculae apparent. Bone formation rate (BFR/BS) was also lower in MPS VI animals than controls (0.0011 mm3/mm2 per day vs. 0.008 mm3/mm2 per day, respectively). Vertebral and tibial bone length in MPS VI animals progressively fell behind normal values with increasing age, as did cortical bone thickness. Vertebral body shape was also altered. ERT with recombinant human 4S (rh4S) resulted in a vertebral BV/TV of 8.23% in animals treated with an intravenous enzyme dose of 1 mg/kg and a BV/TV of 14.33% in animals treated with a dose of 5 mg/kg. BFR/BS also increased to 0.0034 mm3/mm2 per day in animals treated with enzyme doses of either 1.0 or 5.0 mg/kg rh4S. All other affected histomorphometric parameters also improved with ERT to a level intermediate between MPS VI untreated animals and normals. However, individual animals treated with 0.2 mg/kg rh4S intravenously or 1.0 mg/kg rh4S administered subcutaneously did not exhibit an improvement over untreated MPS VI animals. Vertebral and tibial bone lengths, tibial cortical bone thickness, and vertebral body shape also responded to ERT, with a trend away from the untreated group. Thus, ERT had a positive effect on bone development in MPS VI animals that was dependent upon the dose of enzyme administered and the route of administration.

Animals↗
PubMed1988

Immunohistochemical localization of native and denatured collagen types I and II in fetal and adult rat long bones.

Collagen turnover during rat long bone development and growth was investigated using immunofluorescence methods with specific polyclonal antibodies against native (triple helix) and denatured (breakdown products) forms of type I and II collagen. Labeling of cryostat sections with anti-native and denatured collagen type II antibodies resulted in a positive staining throughout the cartilage matrix of fetal and adult long bones. Likewise, native and denatured type I collagen could be detected in mineralized and non-mineralized bone matrix. Moreover, labeling with anti-denatured type I antibody evoked a strong intracellular staining of osteoblasts, but not of osteocytes. Denatured type I was also localized intra-pericellularly in the small chondrocytes comprising the primitive cartilage cores and the epiphyses of older long bones. On the other hand, apart from its localization in the cartilage matrix, denatured type II collagen was found specifically within the chondrocytes. These observations indicate that a continuous turnover of the major collagen types takes place in fetal and adult rat long bone tissue. Degradation of collagen apparently occurs intra- and extracellularly, and is mainly independent of the presence and activity of osteoclasts. The presence of denatured type I collagen in cartilage suggests that chondrocytes synthesize small amounts of type I collagen, which is immediately degraded to a denatured form.

Animals↗
PubMed2006

Early lymphocyte development in bone marrow and thymus.

Haematopoietic stem cells (HSCs), a very rare cell type in the bone marrow, are responsible for the life-long production of all cells of the blood including T and B cells. Until recently, it was thought that the differentiation of HSCs into the various haematopoietic cells was rather hierarchical in that differentiation along a given lineage was associated with a progressive loss of potential to give rise to other blood cell lineages. The recent development of very sensitive and quantitative in vitro assays, together with the identification of new progenitor subpopulations, has challenged this idea. Thus, lymphocyte progenitors can be shown to keep their developmental potential to give rise to myeloid, dendritic and NK cells until just prior to their final commitment stage. Here we review these new findings and concepts.

Animals↗
PubMed1977

Effects of protein deficiency, pair-feeding, or diet supplementation on maternal, fetal and placental growth in rats.

The effects of feeding, throughout gestation, a diet deficient in protein, of pair-feeding, and of supplementing the deficient diet late in gestation on maternal body weight and weights of the products of conception were investigated in the rat. Protein deprivation resulted in net loss of maternal body weight, smaller and thinner placentas with decreased DNA content and placental labyrinth size, reduced uterine tissue weight, and smaller fetuses with retarded bone development. Pair-feeding caused a less severe reduction in maternal, uterine, placental, and fetal weights. Placentas from pair-fed dams had normal cell numbers with reduced cell size. Diet supplementation late in gestation resulted in increased net and total maternal body weight and uterine, placental, and fetal fetal weights, and an apparent partial recovery in fetal bone development. Placental cell size also increased significantly. The results suggest that placental and uterine development in protein-deficient dams is not the limiting factor in fetal development. Availability of protein may be the primary limiting factor, and energy deficit may play a secondary role.

Animals↗
PubMed1993

Transplant of bone marrow and muscle-derived connective tissue cultures in diffusion chambers for bioassay of bone morphogenetic protein.

To promote a high concentration gradient, syngeneic bone marrow and muscle connective tissue cell cultures and subcultures were exposed to bone morphogenetic protein and associated noncollagenous bone matrix proteins (BMP/NCP) in vitro, transferred to diffusion chambers, and then transplanted into the anterior abdominal wall of isogeneic rats. Both muscle- and marrow-derived cells differentiated into cartilage and chondroosteoid on the inside of diffusion chambers. New bone developed on the vascularized outside surfaces in juxtaposition to avascular tissue on the inside. Levels of glycosaminoglycans (GAGs) and DNA synthesis in tissues inside the chambers were sharply elevated. These data, correlated with histologic observations, demonstrate that the BMP/NCP recruits mesenchymal-type cells for a skeletal tissue pathway of development. Muscle-derived cells, as distinguished from marrow-derived cells, originate in a nonosseous environment but differentiate into osteoprogenitor (osteogenic stem) cells and display levels of DNA synthesis almost as high as marrow stroma-derived cells. The rise in DNA synthesis was maximal in the interval from two to three weeks after transplantation. Whether the bone marrow stroma mesenchymal cell target for BMP is only the osteogenic stem cell population or also includes colony-forming units fibroblasts (CFU-F) remains to be investigated by experiments on established cell lines.

Animals↗
PubMed2004

To go or not to go: Migration of human mesenchymal progenitor cells stimulated by isoforms of PDGF.

The recruitment of mesenchymal progenitor cells (MPCs) and their subsequent differentiation to osteoblasts is mandatory for bone development, remodeling, and repair. To study the possible involvement of platelet-derived growth factor (PDGF) isoforms, primary human MPCs and osteogenic differentiated progenitor cells (dOB) were examined for chemotaxic response to homodimeric human platelet-derived growth factor AA, -BB, and heterodimeric PDGF-AB. The role of PDGF receptors was addressed by preincubation with PDGF receptor alpha and beta chain specific antibodies. Migration of MPCs, dOB, and primary osteoblasts (OB) was stimulated by the addition of rhPDGF-AA, rhPDGF-BB, and rhPDGF-AB. The effect was highest in MPCs and for rhPDGF-BB, and declining with osteogenic differentiation. Preincubation with the receptor alpha specific antibody decreased the CI to borderline values while pretreatment with the receptor beta specific antibody led to a complete loss of chemotactic response to PDGF isoforms. In control experiments, basal migration values and rhBMP-2 as well as rxBMP-4 induced chemotaxis of MPC were not influenced by the addition of receptor alpha or beta antibodies. Interestingly, without preincubation the parallel exposure of MPC to rhTGF-beta1 instantaneously leads to a selective loss of migratory stimulation by rhPDGF-AA. The chemotactic effect of PDGF isoforms for primary human MPCs and the influence of osteogenic differentiation suggest a functional role for recruitment of MPCs during bone development and remodeling. Moreover, these observations may be useful for novel approaches towards guided tissue regeneration or tissue engineering of bone.

Adult↗
PubMed1983

Ammonium polyphosphate versus dicalcium phosphate as a phosphorus supplement for growing-finishing swine.

A totaL of 160 crossbred pigs were fed a sorghum-soybean meal diet with ammonium polyphosphate (APP) or dicalcium phosphate (DiCa) as supplemental phosphorus (P) sources for growing-finishing swine. The diets contained P levels of .5 and .4% for the grower phase and .4 and .33% for the finisher phase. Ammonium polyphosphate was evaluated on the basis of pig performance and bone development and compared with DiCa as a standard. The first rib and third and fourth metacarpals were removed from eight barrows from each of the four treatments. Replacement of DiCa with APP as the P supplement did not affect (P greater than .05) average daily gain, average daily feed and feed:gain ratio of growing-finishing pigs. No effect on bone variables examined on the first rib and third and fourth metacarpals was obtained between pigs fed APP or DiCa. Pigs on the lower supplemental P levels had lower (P less than .05) dry fat-free weight and percentage ash for all three bones. The breaking force of the first rib was less (P less than .05) for the pigs fed the lower P supplements of APP and DiCa than for pigs fed the higher level of DiCa. A trend was observed for an apparent decreased P availability from APP than DiCa when fed at the lower level of supplementation, but this trend was not observed when APP was added to provide a P level to meet National Research Council requirements. Ammonium polyphosphate as a P supplement for growing-finishing swine was satisfactory for performance and bone mineralization as compared with DiCa.

Animals↗
PubMed1999

Dietary carbohydrates and fat influence radiographic bone mineral content of growing foals.

Hydrolyzable carbohydrate intake in horse diets may become excessive when rapidly growing pastures are supplemented with grain-based concentrates. The substitution of fat and fiber for hydrolyzable carbohydrate in concentrates has been explored in exercising horses but not in young, growing horses. Our objective was to compare bone development in foals that were fed pasture and concentrates rich in sugar and starch (corn, molasses) or fat and fiber (corn oil, beet pulp, soybean hulls, oat straw). Forty foals were examined, 20 each in 1994 and 1995. In each year, 10 mares and their foals were fed a corn and molasses supplement (SS) and 10 others were fed a corn oil and fiber supplement (FF). The concentrates were formulated to be isocaloric and isonitrogenous, and mineral content was balanced to complement the pastures and meet or exceed NRC requirements. Dorsopalmar radiographs were taken of the left third metacarpal monthly from birth to weaning and then every other month until 1 yr of age. Bone density was estimated using imaging software and an aluminum stepwedge. Radiographic examination indicated differences in medial, lateral, and central bone mineral content of the metacarpal III. Bone mineral content increased with age, and a plateau was observed during winter. Bone mineral content was lower in weanlings and yearlings fed the FF supplement than in those fed SS. Subjective clinical leg evaluations indicated differences in physitis, joint effusion, and angular and flexural limb deformities in response to age, and possibly to season. Regression analysis indicated positive relationships between bone mineral content and body weight, age, and body measurements. Nutrient and chemical interactions, such as the binding of calcium by fat and fiber, may alter the availability of elements necessary for bone development.

Animal Feed↗