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  • 1
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    CXCL12/CXCR4 signaling in the osteoblast regulates the mesenchymal stem cell and osteoclast lineage populations [Research Communications] (2013)
    The Federation of American Societies for Experimental Biology (FASEB)
    Details
    Publication Date: 2013-08-30
    Description: The chemokine CXCL12 and its receptor CXCR4 play a key role in regulation of hematopoietic stem cells and cell migratory function during morphogenesis. Osteoblasts express both the ligand and the receptor, but little is known about the role of CXCL12-CXCR4 signaling in maintaining skeletal homeostasis. Using Cre-Lox technology to delete CXCR4 in mature osteoblasts in mice, we show here a significant decrease in bone mass and alterations in cancellous bone structure. CXCR4 gene ablation increased the number of colony-forming units (CFU), CFU-positive for alkaline phosphatase (CFU-AP + ), and mineralizing nodules in bone marrow stromal cell (BMSC) cultures. The adipocyte precursor population decreased in BMSCs harvested from the KO animals. The nonadherent population of BMSCs harvested from the long bone diaphysis of KO animals formed more osteoclasts, a finding that was associated with increased circulatory levels of pyridinoline, a marker of bone resorption. Our data show that osteoblast-specific CXCR4 deletion has profound effects on the mesenchymal stem cell pool and allocation to the osteoblastic and adipocytic cell lineages. They also show that CXCL12/CXCR4 signaling in the mature osteoblast can feedback to regulate the osteoclast precursor pool size and play a multifunctional role in regulating bone formation and resorption.—Shahnazari, M., Chu, V., Wronski, T. J., Nissenson, R. A., Halloran, B. P. CXCL12/CXCR4 signaling in the osteoblast regulates the mesenchymal stem cell and osteoclast lineage populations.
    Print ISSN: 0892-6638
    Electronic ISSN: 1530-6860
    Topics: Biology
    Published by The Federation of American Societies for Experimental Biology (FASEB)
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  • 2
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    Soluble IL-6 Receptor Signaling and PTH in Marrow [Metabolism] (2013)
    The American Society for Biochemistry and Molecular Biology (ASBMB)
    Details
    Publication Date: 2013-03-09
    Description: Both PTH and IL-6 signaling play pivotal roles in hematopoiesis and skeletal biology, but their interdependence is unclear. The purpose of this study was to evaluate the effect of IL-6 and soluble IL-6 receptor (sIL-6R) on hematopoietic and skeletal actions of PTH. In the bone microenvironment, PTH stimulated sIL-6R protein levels in primary osteoblast cultures in vitro and bone marrow in vivo in both IL-6+/+ and IL-6−/− mice. PTH-mediated hematopoietic cell expansion was attenuated in IL-6−/− compared with IL-6+/+ bone marrow, whereas sIL-6R treatment amplified PTH actions in IL-6−/− earlier than IL-6+/+ marrow cultures. Blocking sIL-6R signaling with sgp130 (soluble glycoprotein 130 receptor) inhibited PTH-dependent hematopoietic cell expansion in IL-6−/− marrow. In the skeletal system, although intermittent PTH administration to IL-6+/+ and IL-6−/− mice resulted in similar anabolic actions, blocking sIL-6R significantly attenuated PTH anabolic actions. sIL-6R showed no direct effects on osteoblast proliferation or differentiation in vitro; however, it up-regulated myeloid cell expansion and production of the mesenchymal stem cell recruiting agent, TGF-β1 in the bone marrow microenvironment. Collectively, sIL-6R demonstrated orphan function and mediated PTH anabolic actions in bone in association with support of myeloid lineage cells in the hematopoietic system.
    Print ISSN: 0021-9258
    Electronic ISSN: 1083-351X
    Topics: Biology , Chemistry and Pharmacology
    Published by The American Society for Biochemistry and Molecular Biology (ASBMB)
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  • 3
    Electronic Resource
    Electronic Resource
    Skeletal effects of withdrawal of estrogen and diphosphonate treatment in ovariectomized rats (1993)
    Springer
    Calcified tissue international 53 (1993), S. 210-216 
    Details
    ISSN: 1432-0827
    Keywords: Ovariectomy ; Bone Histomorphometry ; Osteopenia ; Estrogen ; Diphosphonates
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary The study was designed to determine the skeletal effects of withdrawal of estrogen and diphosphonate treatment in the estrogen-deplete state. Groups of ovariectomized (OVX) rats were treated with vehicle alone, estrogen, or the diphosphonates etidronate or risedronate for a 180-day period. A group of sham-operated control rats was treated for 180 days with vehicle alone. All treatments were then terminated, followed by sequential sacrifice of rats at 0, 35, 90, 180, and 360 days after withdrawal of treatment. The proximal tibia from each animal was processed undecalcified for quantitative bone histomorphometry. At the end of the treatment period, vehicle-treated OVX rats were characterized by cancellous osteopenia and increased bone turnover relative to vehicle-treated control rats. Treatment of OVX rats with estrogen or diphosphonates depressed bone turnover and protected against cancellous osteopenia. During the withdrawal period, OVX rats previously treated with estrogen exhibited rapid bone loss associated with increased bone turnover. The bone protective effect of the hormone in OVX rats was nearly completely lost by 90 days of withdrawal. In contrast, OVX rats maintained low levels of bone turnover and normal cancellous bone mass at 180 days of withdrawal from diphosphonate treatment. The results suggest that estrogen-deplete women who are withdrawn from estrogen replacement are at high risk for subsequent bone loss. They further suggest that widely spaced periods of intermittent diphosphonate treatment may be sufficient to prevent the development of osteopenia in postmenopausal and oophorectomized women.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01321840
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  • 4
    Electronic Resource
    Electronic Resource
    Calcitonin Provides Complete Protection Against Cancellous Bone Loss in the Femoral Neck of Ovariectomized Rats (1997)
    Springer
    Calcified tissue international 60 (1997), S. 457 -461 
    Details
    ISSN: 1432-0827
    Keywords: Key words: Cancellous bone — Histomorphometry — Calcitonin — Femoral neck — Ovariectomy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Abstract. Calcitonin (CT) has been found to partially prevent cancellous bone loss in the proximal tibia of ovariectomized (OVX) rats. The current study was designed to determine whether CT has similar bone protective effects in the femoral neck, a skeletal site with a slower rate of bone loss after ovariectomy than the proximal tibia. Female Sprague Dawley rats were sham-operated or ovariectomized at 3 months of age. Groups of OVX rats were injected s.c. with vehicle or CT at a dose of 16 U/kg body weight on alternate days for 30, 60, or 90 days. Sham-operated control rats were treated with vehicle alone on alternate days. The proximal femur from each rat was processed undecalcified for quantitative bone histomorphometry. Cancellous bone volume in the femoral neck of vehicle-treated OVX rats was significantly less than that of vehicle-treated control rats at all time points. This cancellous osteopenia induced by ovariectomy was associated with increased indices of bone turnover such as osteoclast surface, osteoblast surface, and bone formation rate (tissue level, total surface referent). In contrast, cancellous bone volume in the femoral neck of CT-treated OVX rats was nearly identical of that of vehicle-treated control rats throughout the study. In addition, CT treatment of OVX rats decreased all indices of bone turnover to near the level of vehicle-treated control rats. The results indicate that CT treatment depresses bone turnover and provides complete protection against moderate cancellous osteopenia in the femoral neck of OVX rats. Since previous studies have shown that CT only partially protects against more pronounced cancellous bone loss in the proximal tibia of OVX rats, our findings suggest that CT has a greater bone protective effect at a skeletal site with a slower rate of cancellous bone loss (femoral neck) than at a skeletal site with a rapid rate of cancellous bone loss (proximal tibia).
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002239900262
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  • 5
    Electronic Resource
    Electronic Resource
    Variations in mineral apposition rate of trabecular bone within the beagle skeleton (1981)
    Springer
    Calcified tissue international 33 (1981), S. 583-586 
    Details
    ISSN: 1432-0827
    Keywords: Tetracycline ; Trabecular bone ; Mineral apposition rate ; Bone marrow ; Vascularity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine , Physics
    Notes: Summary 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〈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±0.3µm/day, while that in the latter 2 was 0.9±0.2µm/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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02409495
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  • 6
    Electronic Resource
    Electronic Resource
    Long-term osteopenic changes in cancellous bone structure in ovariectomized rats (1993)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 236 (1993), S. 433-441 
    Details
    ISSN: 0003-276X
    Keywords: Bone ; Cancehous bone ; Osteopenia ; Ovariectomy ; Morphometry ; Rats ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Cancellous bone mass decreases following ovariectomy in rodents, providing a useful model for post-menopausal bone loss in humans. This study describes and quantifies the longer-term changes in cancellous bone structure in the ovariectomized (OVX) rat. Rats were OVX or sham-OVX at 100 days of age and bones were collected 540 days later. Lumbar vertebral bodies were prepared for microradiography and structural analyses (nodal analyses and star volume analyses) of cancellous bone. Proximal humerii were prepared for scanning electron microscopy (SEM). Microradiography confirmed the loss of cancellous bone from the central spongiosa regions of the vertebral bodies and the humerii in the OVX rats. Changes in trabecular structural elements included relative increases in the number of free to free, cortical to free, cortical to node struts and decreases in the node to node struts in the OVX animals compared with controls. There were increases in average lengths of the node to free, node to node, and free to free trabecular struts in the OVX animals. The marrow star volume was increased in the OVX animals indicating a greater trabecular separation in these animals compared with controls. Viewed by SEM, metaphyseal trabeculae in the controls consisted of rods and plates but in the OVX animals the remaining trabeculae were mostly longitudinal rods with smaller transverse connecting rods. The remaining bone in the OVX animals was found in the lateral metaphyseal areas and is consistent with maintenance of the structural capacity of the bone. These long-term changes in cancellous bone structure are likely due to the continuation of functional skeletal loading but a decrease in gonadal hormones resulting in a decreased necessity to maintain a skeletal mineral store for reproduction (e.g., pregnancy and lactation). © 1993 Wiley-Liss, Inc.
    Additional Material: 10 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1092360303
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