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At least 181 records · Page 10Linked to original sources
PubMed1998

Control of cell cycle gene expression in bone development and during c-Fos-induced osteosarcoma formation.

We have used c-Fos transgenic mice which develop osteosarcomas to determine the expression patterns of cyclins, cyclin-dependent kinases (CDKs), and cyclin-dependent kinase inhibitors (CKIs) in different bone cell populations in order to define the potential mechanisms of c-Fos transformation. Immunohistochemical analysis in embryonic and early postnatal bone demonstrated that cyclin E and its kinase partner CDK2 were expressed specifically in bone-forming osteoblasts. Cyclin D1 expression was absent despite high levels of CDK4 and CDK6, and the CKI p27 was expressed in chondrocytes, osteoclasts, and at lower levels in osteoblasts. Following activation of the c-fos transgene in vivo and before overt tumor formation, cyclin D1 expression increased dramatically and was colocalized with exogenous c-Fos protein specifically in osteoblasts and chondrocytes, but not in osteoclasts. Prolonged activation of c-Fos resulted in osteosarcoma formation wherein the levels of cyclin D1, cyclin E, and CDKs 2, 4, and 6 were high in a wide spectrum of malignant cell types, especially in transformed osteoblasts. The CKI p27 was expressed at very high levels in bone-resorbing osteoclasts, and to a lesser extent in chondrocytes and osteoblasts. These in vivo observations suggest that cyclin D1 may be a target for c-Fos action and that elevation of cyclin D1 in osteoblasts which already express cyclin E/CDK2 and the cyclin D1 partners CDKs-4 and 6, may predispose cells to uncontrolled cell growth leading to osteosarcoma development. This study implicates altered cell cycle control as a potential mechanism through which c-Fos causes osteoblast transformation and bone tumor formation.

Animals↗
PubMed1988

The influence of a high-protein, low-carbohydrate diet on bone development in the fetuses of rat dams with streptozotocin-induced diabetes.

1. The purpose of the present study was to determine the effects of diet on the mandibles and growth centres of the long bones in the fetuses of diabetic rat dams given a normal diet compared with those given a high-protein, low-carbohydrate diet. 2. On the 9th day of gestation, the controls, groups 1 and 3, were injected with citrate buffer and given 200 and 600 g protein/kg diets respectively. Groups 2 and 4 were injected with 40 mg streptozotocin/kg body-weight and pair-fed with groups 1 and 3 respectively on the 200 and 600 g protein/kg diets. 3. On day 22, some dams were injected with either 45Ca or [14C]proline. Mandibles and long bones were removed and weighed and analysed for Ca content, 45Ca uptake, collagen and collagen synthesis. 4. The body-weights, and mandibular and long-bone weights of the fetuses in the diabetic 200 g protein/kg group were smaller than those of the non-diabetic 200 g protein/kg group, whereas those of the diabetic 600 g protein/kg group showed no difference from the non-diabetic 600 g protein/kg group. 5. The rate of collagen synthesis was higher in the fetuses of the diabetic 600 g protein/kg group than those of the non-diabetic group. Bones of the diabetic 200 g protein/kg group were lower in collagen content when compared with the non-diabetic group, whereas there was no difference between the diabetic and non-diabetic 600 g protein/kg groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Transcription factor ERG variants and functional diversification of chondrocytes during limb long bone development.

During limb development, chondrocytes located at the epiphyseal tip of long bone models give rise to articular tissue, whereas the more numerous chondrocytes in the shaft undergo maturation, hypertrophy, and mineralization and are replaced by bone cells. It is not understood how chondrocytes follow these alternative pathways to distinct fates and functions. In this study we describe the cloning of C-1-1, a novel variant of the ets transcription factor ch-ERG. C-1-1 lacks a short 27-amino acid segment located approximately 80 amino acids upstream of the ets DNA binding domain. We found that in chick embryo long bone anlagen, C-1-1 expression characterizes developing articular chondrocytes, whereas ch-ERG expression is particularly prominent in prehypertrophic chondrocytes in the growth plate. To analyze the function of C-1-1 and ch-ERG, viral vectors were used to constitutively express each factor in developing chick leg buds and cultured chondrocytes. We found that virally driven expression of C-1-1 maintained chondrocytes in a stable and immature phenotype, blocked their maturation into hypertrophic cells, and prevented the replacement of cartilage with bone. It also induced synthesis of tenascin-C, an extracellular matrix protein that is a unique product of developing articular chondrocytes. In contrast, virally driven expression of ch-ERG significantly stimulated chondrocyte maturation in culture, as indicated by increases in alkaline phosphatase activity and deposition of a mineralized matrix; however, it had modest effects in vivo. The data show that C-1-1 and ch-ERG have diverse biological properties and distinct expression patterns during skeletogenesis, and are part of molecular mechanisms by which limb chondrocytes follow alternative developmental pathways. C-1-1 is the first transcription factor identified to date that appears to be instrumental in the genesis and function of epiphyseal articular chondrocytes.

Alkaline Phosphatase↗
PubMed2001

Characterization of a novel KRAB/C2H2 zinc finger transcription factor involved in bone development.

Osteogenic differentiation involves a cascade of coordinated gene expression that regulates cell proliferation and matrix protein formation in a defined temporo-spatial manner. Here we have used differential display to identify a novel zinc finger transcription factor (AJ18) that is induced during differentiation of bone cells in vitro and in vivo. The 64-kDa protein, encoded by a 7- kilobase mRNA, contains a Krüppel-associated box (KRAB) domain followed by 11 successive C(2)H(2) zinc finger motifs. AJ18 mRNA, which is also expressed in kidney and brain, is developmentally regulated in embryonic tibiae and calvariae, with little expression in neonate and adult animals. During osteogenic differentiation in vitro AJ18 mRNA is expressed as cells approach confluence and declines as bone formation occurs. Using bacterially expressed, His-tagged AJ18 in a target detection assay, we identified a consensus binding sequence of 5'-CCACA-3', which forms part of the consensus element for Runx2, a master gene for osteogenic differentiation. Overexpression of AJ18 suppressed Runx2-mediated transactivation of an osteocalcin promoter construct in transient transfection assays and reduced alkaline phosphatase activity in bone morphogenetic protein-induced C3H10T1/2 cells. These studies, therefore, have identified a novel zinc finger transcription factor in bone that can modulate Runx2 activity and osteogenic differentiation.

Amino Acid Sequence↗
PubMed2001

Expression of the novel transcription factor OASIS, which belongs to the CREB/ATF family, in mouse embryo with special reference to bone development.

The OASIS gene, which encodes a novel CREB/ATF family member, was isolated from long-term cultured astrocytes that were employed as an in vitro gliosis model. In the present study, we examined the expression pattern of the OASIS gene in the developing mouse embryo by in situ hybridization histochemistry and compared it with the expression of osteogenesis markers. OASIS mRNA expression was most strongly detected in preosteoblasts of the outer bony cortex of the ribs. Alveolar bone also showed strong signals for OASIS gene expression. OASIS mRNA was also localized to the preodontoblast of tooth buds. Expression began at embryonic day 12 (D12.5), peaked around D14.5-16.5, and continued to D18.5. The pattern of expression was very similar to that of hXBP-1 mRNA, which encodes another CREB/ATF family member. Spatiotemporal patterns of OASIS partly overlapped that of osteopontin, osteonectin, and alpha1 type I procollagen genes. Among these, the time course of OASIS mRNA expression was most similar to that of osteopontin mRNA expression, suggesting that the OASIS protein is involved in the late phase of osteoblast differentiation, as compared to the Cbfa1 that regulates early phases of osteoblast differentiation.

Animals↗
PubMed1992

Morphological changes in long bone development in fetal akinesia deformation sequence: an experimental study in curarized rat fetuses.

In order to investigate the transverse growth of the long bones during intrauterine development in the fetal akinesia deformation sequence (FADS), we studied curarized rat fetuses. Curarization was performed by daily subcutaneous administration of D-Tubocurarine from day 17 of gestation until term. Experimental fetuses were compared with a sham-operated control group. The total area and perimeter, the absolute and relative amount of periosteum and bone trabeculae, the major and minor axes, and the elongation factor were measured from histological cross-sections of the femoral metaphysis and diaphysis using an IBAS 1 image analysis system. Curarized rat fetuses showed growth retardation, a short umbilical cord, and multiple articular contractures, a phenotype consistent with FADS. Alterations in femoral shape and transverse growth that affected the diaphysis were noted in these fetuses. These included a decrease of total cross-section area and reduction of the absolute and relative amounts of bone trabeculae with marked thinning of the periosteum. Femoral cross-sections was rounder than controls. These results evidenced an impairment of the membraneous (periosteal) ossification of long bones produced by immobilization and/or decrease of muscular strength, and support our previous clinical findings of bone hypoplasia and osteopenia in FADS.

Animals↗
PubMed2000

Bone development.

Early development of the vertebrate skeleton depends on genes that pattern the distribution and proliferation of cells from cranial neural crest, sclerotomes, and lateral plate mesoderm into mesenchymal condensations at sites of future skeletal elements. Within these condensations, cells differentiate to chondrocytes or osteoblasts and form cartilages and bones under the control of various transcription factors. In most of the skeleton, organogenesis results in cartilage models of future bones; in these models cartilage is replaced by bone by the process of endochondral ossification. Lastly, through a controlled process of bone growth and remodeling the final skeleton is shaped and molded. Significant and exciting insights into all aspects of vertebrate skeletal development have been obtained through molecular and genetic studies of animal models and humans with inherited disorders of skeletal morphogenesis, organogenesis, and growth.

Animals↗
PubMed1983

Effect of low salt, sodium, and chloride levels in poult rations on growth, bone development, and related factors.

Two 4-week trials were conducted to determine the role of sodium chloride (salt) on field rickets in poults. A comparison of added dietary salt at 0, .075, .10, .25, and .45% to a corn-soy basal with .103% salt showed significant differences (P less than .05) in body weight gains, blood calcium, magnesium and sodium, feed conversion, and adrenal gland weights among the treatments. Mortality and abnormal bone scores decreased with increasing salt. When sodium was added to the basal diet as a single element for the poults at either 0, .09, .10, .11, and .12%, or chloride at 0, .009, .01, .02, and .03% in comparison to a control group with .20% sodium and .30% chloride, significant differences were found in weekly gain, bone ash, bone breaking strength, tibia weight/body weight, and serum alkaline phosphatase levels between the sodium, chloride, and the combined element groups. Bone abnormality scores decreased with increasing levels of both sodium and chloride in diets.

Animals↗
PubMed1995

Species differences in uroepithelium-induced bone development: observations on transplants of human uroepithelium in cortisone-treated mice.

Specimens (2-3 x 3-5 mm) of human urinary tract mucosa from bladder (67 cases), ureter and renal pelvis (35 cases) were implanted intramuscularly into cortisone-treated mice in order to elucidate whether human urothelium has the potency to induce osteogenesis. Although xenogeneic epithelium survived up to 14 days after implantation, in none of the 300 implants performed was a bone or cartilage induction observed. Implantation of urinary bladder mucosa from guinea pig and dog resulted in a heterotopic bone and cartilage formation in the graft's vicinity in 28 of 39 cases. The survival of animal transitional epithelium was similar to that of human. It is concluded that human transitional epithelium does not possess osteoinductive potency. Some clinical data pointing to a link between heterotopic osteogenesis and surgical intervention on urinary tract have been reconsidered and explained by the authors' own hypothesis. In addition, data presented in this paper indicate that one should be very careful when attempting to transmit results performed on dog urinary tract to humans.

Adult↗
PubMed1988

The influence of supplemental feed on growth and bone development of nursing foals.

Thirty foals of mixed breeding, from two consecutive years, were used in two 120-d experiments to evaluate the effects of supplemental feeding (creep feed) on growth in nursing foals. At 10 d postpartum, foals were randomly assigned either to a creep-fed group (CF) or an unsupplemented group (NCF). Initial measurements of body weight (BW), height at the withers (WH), third metatarsal length (MtIII) and third metacarpal length (McIII) were made at 10 d of age and at 30-d intervals thereafter. Medial and lateral cortical peak values for radiographic bone density, cortical width and cortical area at the midpoint of the third metacarpal were used to assess bone quality. Creep feed containing National Research Council (NRC, 1978) recommended levels for all nutrients was offered at 1.5% of BW per day. When compared with unsupplemented foals, supplemented foals had greater gains in BW (P less than .05), in WH (P less than .10) and in MtIII (P less than .05). Mean gains during the trial in BW, WH, MtIII and McIII for the CF foals were 133.3 kg, 22.8 cm, 2.1 cm and 1.9 cm and for the NCF foals were 117.6 kg, 21.2 cm, 1.5 cm and 1.9 cm, respectively. The mean value for the lateral cortical peak was slightly lower (P less than .10) for the CF foals. No differences (P greater than .10) were observed for the medial cortical peak, cortical width or cortical area of the third metacarpal. The results of this study indicate that a creep feeding program that supplies NRC-recommended nutrient levels can increase the rate of skeletal growth with little decrease in quality of bone.

Animal Feed↗