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At least 577 records · Page 32Linked to original sources
PubMed1992

Influence of short-term aluminum exposure on demineralized bone matrix induced bone formation.

The effects of aluminum exposure on bone formation employing the demineralized bone matrix (DBM) induced bone development model were studied using 4-week-old Sprague-Dawley rats injected with a saline (control) or an aluminum chloride (experimental) solution. After 2 weeks of aluminum treatment, 20-mg portions of rat DBM were implanted subcutaneously on each side in the thoracic region of the control and experimental rats. Animals were killed 7, 12, or 21 days after implantation of the DBM and the developing plaques removed. No morphological, histochemical, or biochemical differences were apparent between plaques from day 7 control and experimental rats. Plaques from day 12 control and experimental rats exhibited cartilage formation and alkaline phosphatase activity localized in osteochondrogenic cells, chondrocytes, osteoblasts, and extracellular matrix. Unlike the plaques from control rats that contained many osteoblastic mineralizing fronts, the plaques from the 12-day experimental group had a preponderance of cartilaginous tissue, no evidence of mineralization, increased levels of alkaline phosphatase activity, and a reduced calcium content. Plaques developing for 21 days in control animals demonstrated extensive new bone formation and bone marrow development, while those in the experimental rats demonstrated unmineralized osteoid-like matrix with poorly developed bone marrow. Alkaline phosphatase activity of the plaques continued to remain high on day 21 for the control and experimental groups. Calcium levels were significantly reduced in the experimental group. These biochemical changes correlated with histochemical reductions in bone calcification.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed2002

Lumican is a major proteoglycan component of the bone matrix.

MC3T3-E1 mouse calvaria cells are a clonal population of committed osteoprogenitors that in the presence of appropriate supplements form a mineralized bone matrix. The development of the MC3T3-E1 cells can be divided into three major stages, namely, proliferation, differentiation, and mineralization. Recently, using the cDNA microarray technology we found lumican to be abundantly expressed during the mineralization and differentiation stages of the MC3T3-E1 development and not during the proliferation stage. Lumican has been shown to play essential roles in regulating collagen fibril formation in different extracellular matrices but its expression in the developing bone matrix remains elusive. By examining the expression profile of this gene during the different stages of MC3T3-E1 development, utilizing the 'real-time' PCR technology, we observed that the expression of lumican increases as the osteoblast culture differentiates and matures, suggesting that lumican may be involved in regulating collagen fibrillogenesis in bone matrices. Using immunostaining, we observed that during the early embryonic development of mouse (E11 to E13), lumican is mainly expressed in the cartilaginous matrices. However, in the older embryos (E14 to E16), the expression of lumican is more prominent in the developing bone matrices. Our data suggest that lumican is a significant proteoglycan component of bone matrix, which is secreted by differentiating and mature osteoblasts only and therefore it can be used as a marker to distinguish proliferating pre-osteoblasts from the differentiating osteoblasts.

Animals↗
PubMed2000

Addition of the BMP4 antagonist, noggin, disrupts avian inner ear development.

Bone morphogenetic protein 4 (BMP4) is known to regulate dorsoventral patterning, limb bud formation and axis specification in many organisms, including the chicken. In the chick developing inner ear, BMP4 expression becomes localized in two cell clusters at the anterior and posterior edges of the otic epithelium beginning at stage 16/17 and is expressed in presumptive sensory tissue at later stages. This restricted spatiotemporal pattern of expression occurs just prior to the otocyst's transition to a more complex three-dimensional structure. To further analyze the role of BMP4 in avian otic morphogenesis, cells expressing BMP4 or its antagonist, noggin, were grown on agarose beads and implanted into the periotic mesenchyme surrounding the chick otocyst. Although the BMP4-producing cells had no effect on the mature inner ear structure when implanted alone, noggin-producing cells implanted adjacent to the BMP4 cell foci prevented normal semicircular canal development. Beads implanted at the anterior BMP4 focus eliminated the anterior and/or the horizontal canals. Noggin cells implanted at the posterior focus eliminated the posterior canal. Canal loss was prevented by co-implantation of BMP4 cell beads next to noggin beads. An antibody to the chick hair cell antigen (HCA) was used to examine sensory cell distribution, which was abnormal only in the affected tissues of noggin-exposed inner ears. These data suggest a role for BMP4 in the accurate and complete morphological development of the semicircular canals.

Animals↗
PubMed2006

The role of Wnts in bone metastases.

Wnts are a large family of secreted glycoproteins that mediate bone development in the embryo and promote bone production in the adult. Autocrine Wnt signaling within tumor cells has been shown to promote tumorigenesis by enhancing tumor cell proliferation and survival. We recently demonstrated that prostate cancer cells (CaP) produce Wnts which act in a paracrine fashion to induce osteoblastic activity in CaP bone metastases. The ability of tumor-derived Wnts to influence bone development is regulated by multiple families of secreted antagonists including soluble frizzled related receptors (sFrp) and dickkopfs (DKK). CaP cells appear to produce DKK-1 early in the development of skeletal metastases, which masks osteogenic Wnts and thus favors an osteolytic environment at the metastatic site. As the metastases progresses, DKK-1 expression is lost allowing for a Wnt mediated osteoblastic response which predominates CaP boney lesions. Interestingly, blocking DKK-1 expression early in CaP metastasis prevents tumor establishment within the bone suggesting that osteolysis is a required first step in the development of CaP bone metastases. In this review, we discuss our data on the Wnt inhibitor DKK-1 in CaP bone metastasis in the context of current literature evidence that demonstrate that Wnt inhibitors can function as both tumor suppressors and tumor promoters. We provide a model that the affect of Wnt inhibitors on tumor development is dependent on the tumor micro-environment and suggest that DKK-1 is a switch which transitions CaP bone metastases from osteolytic to osteoblastic.

Animals↗
PubMed1974

The effect of cells transferred into the mouse blastocyst on subsequent development.

Bone marrow cells from CBA T6T6 mice and testicular teratocarcinoma cells from 129 SvSl mice were transferred into blastocysts from random-bred Swiss albino mice. The blastocysts were allowed to develop in foster mothers and the adults resulting from these blastocysts were studied for evidence of an effect of the transferred cells. A total of 137 adults resulted from the experiments, and one of the mice that had received teratocarcinoma cells in the blastocyst stage showed several thin stripes of agouti hair. All the adult animals received grafts of skin from animals identical to those supplying the cells. In all cases the animals that resulted from blastocysts into which cells had been transferred maintained skin grafts for a significantly longer period than controls. In a number of cases the graft developed agouti hair and in two cases the graft was maintained for approximately 2 mo. These experiments indicate that the transferred cells were able to establish small colonies in the embryos and that some of these cells persisted into the adult.

Animals↗
PubMed1994

Expression of mRNA of murine bone-related proteins in ectopic bone induced by murine bone morphogenetic protein-4.

To determine whether a system of ectopic bone formation induced by osteosarcoma-derived bone-inducing substance (bone morphogenetic protein-4) can be used as a model of developing bone at the molecular level, we studied the expression of bone-related protein mRNAs in the process of ectopic bone formation using non-radioisotopic in situ hybridization. Osteonectin mRNA was detected in fibroblast-like cells, which are similar to periosteal cells from the early to middle stages of bone development. The proportion of osteonectin mRNA-expressing cells was greater than that of osteopontin mRNA-expressing cells in hypertrophic chondrocytes and osteoblast-like cells. In contrast, osteopontin mRNA was localized in a limited population of hypertrophic chondrocytes, a single layer of osteoblast-like cells adjacent to the bone trabeculae in the middle stage of bone formation, and in a limited subset of osteocytes in the late stage. A strong osteocalcin mRNA signal was detected in osteoblast-like cells from the middle to late stages and in a limited subset of osteocytes in the late stage of bone development. Since the sequential gene expression pattern of bone-related proteins in the present system is comparable to that in embryonic osteogenesis, this system may be useful as a model for studying gene expression in osteogenesis.

Animals↗
PubMed1998

[Effect of various levels of vitamin K intake on bone metabolism of rat].

OBJECTIVE: To explore the effect of various levels of vitamin K intake on bone development. METHODS: Forty weanling Wistar male rats were divided into four groups. In one group, 1% sulfadiazine was added to regular diet (vitamin K 50 micrograms/kg) to induce vitamin K deficiency. In the other three groups, the vitamin K levels in diets were 50 micrograms/kg, 300 micrograms/kg, 2,550 micrograms/kg respectively. Twelve weeks later, the rats were killed and the effects of the different levels of vitamin K intake on bone development were evaluated by the parameters of calcium metabolism, bone metabolic biochemistry, and bone mineral density (BMD). RESULTS: Vitamin K did not affect the intestinal absorption of calcium. Vitamin K deficiency led to the high levels of urinary calcium and hydroxyapatite excretion, suggesting an increase of bone absorption. Different levels of dietary vitamin K significantly affect circulating osteocalcin and OCbound content. The level of serum2 osteocalcin, OCbound and BMD elevated with the increase of dietary VK levels, whereas the parameters of PTH (thrombo plastin time) were not different between all groups. CONCLUSION: Vitamin K can enhance the bone development of rat. The rat vitamin K requirement may be higher than that of the current recommendation (50 micrograms/kg).

Animals↗
PubMed1989

Effects of 5-fluorouracil on thymidylate synthase activity and development of bone marrow grafts in spleens of irradiated mice.

The effects of 5-fluorouracil (5-FU) on thymidylate synthase activity and development of myelopoietic tissue in spleens of recipient mice grafted with bone marrow collected from untreated mice, treated with phenylhydrazine or phenylhydrazine and 5-FU were investigated. One dose of 5-FU (100 mg/kg body weight) reduced development of bone marrow grafts from all donors. The activity of thymidylate synthase sharply declined during the first three days after irradiation irrespective of bone marrow transplantation. Next, during consecutive 3 days the activity of the enzyme sharply increased both in mice untreated and treated with 5-FU. The highest thymidylate synthase activity was found in spleens of mice grafted with control bone marrow and next treated with 5-FU. That high enzyme activity appeared in spite of further reduction of spleen weight. Thus, 5-FU prevented completely development of bone marrow grafts in spleens but increased thymidylate synthase activity in a paradoxical manner. Thymidylate synthase in myelopoietic tissue developed from bone marrow, collected in the state of hyperproduction of that enzyme induced with phenylhydrazine and 5-FU, did not show increased resistant to 5-FU.

Animals↗
PubMed1985

Early B cell precursors in long-term bone marrow culture: selective development in the bone marrow of irradiated recipients.

The primary site for the growth and differentiation of B cell precursors in irradiated recipient mice was investigated. Bone marrow (BM) cells from lipopolysaccharide (LPS)-responder C57BL/6 mice were transferred into irradiated LPS-nonresponder C57BL/10ScCr mice, and the generation of donor-derived B cells in the recipient was monitored by determining the immunoglobulin-producing cells developed in the LPS-stimulated cultures of recipient's spleen cells as well as BM cells. As previously stated, the transfer of fresh BM cells resulted in the development of LPS-reactive cells both in spleen and BM simultaneously. On the other hand, when long-term cultured BM cells which were shown to be devoid of B cells and pre-B cells were used as the donor cells, the development of LPS-reactive cells was first observed only in BM, and subsequently in both BM and spleen. The failure to detect LPS-reactive cells in the spleen in the early phase, or day 11 after irradiation and reconstitution, was not attributed to the culture condition or the existence of suppressive activity in day 11 spleen cells. These results indicate that B cell precursors lodge only in the BM of irradiated recipients, grow and differentiate in the same place, and then the differentiated progeny migrate to peripheral lymphoid organs.

Animals↗
PubMed2005

Transgenic zebrafish reveal stage-specific roles for Bmp signaling in ventral and posterior mesoderm development.

Bone morphogenetic protein (Bmp) signaling is crucial for the formation and patterning of zebrafish ventral and posterior mesoderm. Mutants defective in the Bmp pathway have expanded trunk muscle, abnormal tails and severely impaired development of ventral mesodermal derivatives such as vasculature, blood and pronephros. As Bmps continue to be expressed in the ventral and posterior mesoderm after gastrulation, it is likely that Bmp signaling continues to play an important developmental role during outgrowth of the posterior body. However, because Bmp signaling plays an essential role during the gastrula stages, it has not been possible with mutants or standard disruption techniques to determine the later functions of the Bmp pathway. To study the role of Bmp signaling in the ventral and posterior mesoderm during trunk and tail outgrowth, we generated a transgenic zebrafish line containing a heatshock-inducible dominant-negative Bmp receptor-GFP fusion. Our data show that Bmps are important for tail organizer formation and for patterning the ventral mesoderm during early gastrulation. However, from mid-gastrulation to the early somitogenesis stages, Bmp signaling is important for ventral tail fin development and for preventing secondary tail formation. We conclude that the role of Bmp signaling in the ventral and posterior mesoderm changes as gastrulation proceeds.

Animals↗
PubMed1997

Differential expression of BMP receptors in early mouse development.

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor-beta family of polypeptide signaling molecules. They function via binding to two types of transmembrane serine/threonine kinase receptors, type I and type II receptors, that are both necessary for signaling. The expression patterns of the type II BMP receptor (BMPR-II) and three type I BMP receptors (ActR-I, BMPR-IA and BMPR-IB) were examined in preimplantation embryos by means of heminested reverse transcription-polymerase chain reaction (RT-PCR). BMPR-II mRNA was detected in one-cell, two-cell and blastocyst stage embryos. ActR-I exhibited a similar expression pattern. BMPR-IA mRNA however was only detected in blastocysts, whereas BMPR-IB transcripts were detected at all stages from the one-cell zygote to the uncompacted morula, but not in the compacted morula and blastocyst. If translated into proteins, this suggests that different receptor complexes can be formed at different developmental stages. Transcripts for BMPs were not detected in preimplantation embryos, but were detected in the maternal tissues surrounding the embryos. BMPR-II, BMPR-IA and BMPR-IB mRNAs were also detected in undifferentiated and differentiated embryonal carcinoma and embryonic stem cells. In postimplantation embryos BMPR-II transcripts were first detected from 6.0 days post coitum. In situ hybridization analysis revealed that BMPR-II mRNA is ubiquitously expressed in the entire embryo at least until midgestation.

Animals↗
PubMed1994

Development of hemopoietic bone marrow within the ectopic bone induced by bone morphogenetic protein.

Neogenesis of hemopoietic bone marrow was observed in the ectopic bone induced by implantation of bone morphogenetic protein (BMP) into the muscle of mice. A bone rudiment-like cartilage was formed first, which was then replaced by bone through an endochondral ossification process. Bone marrow formation occurred after the invasion of blood vessels into the cartilage, with accumulations of small lymphocyte-like cells and the appearance of large hemopoietic stem cells around the blood vessels. The stem cells proliferated and differentiated to form hemopoietic bone marrow. This process was similar to the embryogenesis of bone and bone marrow, but the hemopoietic activity of the BMP-induced bone was transient. The bone marrow was converted to fatty tissue within 2 weeks of its appearance. This study showed that implantation of BMP in the ectopic sites offers a useful model to investigate the neogenesis of ectopic bone marrow and the regulation of its activity.

Adipose Tissue↗
PubMed2002

Endogenous patterns of BMP signaling during early chick development.

Bone morphogenetic proteins (BMPs) are members of the transforming growth factor beta superfamily signaling molecules that play important roles in a wide variety of developmental processes. In this study, we have used an antibody specific for the phosphorylated and activated form of Smad1 to examine endogenous patterns of BMP signaling in chick embryos during early development. We find complex spatial and temporal distributions of BMP signaling that elucidate how BMPs may function in multiple patterning events in the early chick embryo. In the pregastrula embryo, we find that BMP signaling is initially ubiquitous and is extinguished in the epiblast at the onset of primitive streak formation. At the head process stage, BMP signaling is inactivated in prospective neural plate, while it is strongly activated at the neural plate border, a region which is populated by cells that will give rise to neural crest. During later development, we find a dynamic spatiotemporal activation of BMP signaling along the rostrocaudal axis, in the dorsal neural tube, in the notochord, and in the somites during their maturation process. We discuss the implication of our results for endogenous functions of BMP signaling during chick development.

Animals↗
PubMed1999

Evidence for a role of Smad6 in chick cardiac development.

Bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta (TGF-beta) superfamily, are obligatory growth factors for early embryogenesis and heart formation. SMAD proteins transduce signals of the TGF-beta superfamily. We isolated chicken Smad6 (cSmad6), a member of inhibitory SMADs, and found its expression to be remarkably restricted to the developing heart, eyes, and limbs. cSmad6 expression was detected in the cardiogenic region of stage 5 embryos and overlapped Nkx2-5 and bmp-2, -4, and -7 expression. Throughout development, cSmad6 was expressed strongly in the heart, primarily in the myocardium, endocardium, and endocardial cushion tissue. Myocardial expression of cSmad6 was stronger in the forming septum, where highly localized expression of bmp-2 and -4 was also observed. Ectopically applied BMP-2 protein induced the expression of cSmad6, a putative negative regulator of BMP-signaling pathway, in anterior medial mesoendoderm of stage 4-5 embryos. In addition, blocking of BMP signaling using Noggin downregulated cSmad6 in cardiogenic tissue. cSmad1, one of the positive mediators of BMP signaling, was also expressed in cardiogenic region, but was not BMP-2 inducible. Our data suggest that cSmad6 has a role in orchestrating BMP-mediated cardiac development. We propose the possible mechanism of action of cSmad6 as modulating BMP signal by keeping a balance between constitutively expressed pathway-specific cSmad1 and ligand-induced inhibitory cSmad6 in the developing heart.

Amino Acid Sequence↗
PubMed1995

Childhood malnutrition: an analysis of the effects of nutritional advice.

An analysis of malnutrition was done in 65 infants and preschool children (18 boys and 47 girls) who were under the third percentile of weight for age. Fifty-seven percent of cases has hematocrits of less than 36%, 7% had hematocrits of less than 30% and two had iron deficiency anemia which improved after iron supplement. Eosinophils of more than 400 cells/mm3 were found in 35% of cases. Eleven percent had eosinophils of more than 1,000 cells/mm3. Parasites were found on stool examination in 12.5% of cases. Bone development was retarded in 39% of 23 cases. In 7 cases with bone development delayed more than 6 months, thyroid function and trace elements were analysed and found to be within normal limits. In 5 cases with delayed bone development and height less than 5 cm/year, growth hormones showed normal levels. Proper nutritional advice resulted in improvement in body weight and height in 57% of cases, tricept skin fold in 73%, bicept skin fold in 60%, arm muscle area in 50% and arm fat area in 29% of cases. Improvement was not associated with family income or education of the people who cared for the patients.

Anthropometry↗