scholarly journals Conditional Inactivation of Noggin in the Postnatal Skeleton Causes Osteopenia

Endocrinology ◽  
2012 ◽  
Vol 153 (4) ◽  
pp. 1616-1626 ◽  
Author(s):  
Ernesto Canalis ◽  
Lisa J. Brunet ◽  
Kristen Parker ◽  
Stefano Zanotti
Keyword(s):  
Bone Formation ◽  
Bone Remodeling ◽  
Bone Morphogenetic Proteins ◽  
Detrimental Effect ◽  
Bone Volume ◽  
Developmental Defects ◽  
Femoral Length ◽  
Conditional Inactivation ◽  
Skeletal Homeostasis ◽  
Old Mice

Noggin is an antagonist of bone morphogenetic proteins (BMP), and its overexpression causes suppressed osteoblastogenesis and osteopenia. Global inactivation of Noggin results in severe developmental defects and prenatal lethality, but the consequences of the conditional inactivation of Noggin on the postnatal skeleton are not known. To study the function of noggin in osteoblasts, we generated tissue-specific null Noggin mice by mating Noggin conditional mice, where the Noggin allele is flanked by loxP sequences, with mice expressing the Cre recombinase under the control of the osteocalcin promoter (Oc-Cre). Noggin conditional null mice exhibited decreased weight, shortened femoral length, and generalized osteopenia. Bone histomorphometric and microarchitectural analyses of distal femurs revealed decreased bone volume due to a reduced number of trabeculae in 1- and 3-month-old Noggin conditional null mice. Vertebral microarchitecture confirmed the osteopenia observed in Noggin conditional null mice. Osteoclast number was increased in 1-month-old male Noggin conditional null mice, and bone formation was increased in 3-month-old mice, but female mice did not exhibit increased bone remodeling. In conclusion, Noggin inactivation causes osteopenia, suggesting that BMP in excess have a detrimental effect on bone or that noggin has a BMP-independent role in skeletal homeostasis.

scholarly journals Mice Lacking Bone Sialoprotein (BSP) Lose Bone after Ovariectomy and Display Skeletal Site-Specific Response to Intermittent PTH Treatment

Endocrinology ◽  
2010 ◽  
Vol 151 (11) ◽  
pp. 5103-5113 ◽  
Author(s):  
Ndéye Marième Wade-Gueye ◽  
Maya Boudiffa ◽  
Norbert Laroche ◽  
Arnaud Vanden-Bossche ◽  
Carole Fournier ◽  
...  
Keyword(s):  
Bone Formation ◽  
Trabecular Bone ◽  
Bone Remodeling ◽  
Bone Sialoprotein ◽  
Bone Volume ◽  
Trabecular Bone Volume ◽  
Bone Formation Rate ◽  
Trabecular Thickness ◽  
Skeletal Site ◽  
Intermittent Pth

Bone sialoprotein (BSP) belongs to the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, whose members play multiple and distinct roles in the development, turnover, and mineralization of bone and dentin. The functions of BSP in bone remodeling are not yet well established. We previously showed that BSP knockout (BSP−/−) mice exhibit a higher trabecular bone volume, concomitant with lower bone remodeling, than wild-type (BSP+/+) mice. To determine whether bone turnover can be stimulated in the absence of BSP, we subjected BSP+/+ and BSP−/− mice to catabolic [ovariectomy (OVX)] or anabolic (intermittent PTH administration) hormonal challenges. BSP−/− mice progressively develop hypocalcemia and high serum PTH between 2 and 4 months of age. Fifteen and 30 d after OVX, microtomography analysis showed a significant decrease of trabecular bone volume in tibiae of both genotypes. Histomorphometric parameters of bone formation and resorption were significantly increased by OVX. PTH treatment resulted in an increase of trabecular thickness and both bone formation and resorption parameters at all skeletal sites in both genotypes and a decrease of trabecular bone volume in tibiae of BSP+/+ but not BSP−/− mice. PTH increased cortical thickness and bone area in BSP+/+ but not BSP−/− mice and stimulated the bone formation rate specifically in the endosteum of BSP+/+ mice and the periosteum of BSP−/− mice. PTH enhanced the expression of RANKL, MEPE, and DMP1 in both genotypes but increased OPG and OPN expression only in BSP−/− mice. In conclusion, despite the low basal turnover, both catabolic and anabolic challenges increase bone formation and resorption in BSP−/− mice, suggesting that compensatory pathways are operative in the skeleton of BSP-deficient mice. Although up-regulation of one or several other SIBLINGs is a possible mechanism, further studies are needed to analyze the interplay and cross-regulation involved in compensating for the absence of BSP.

scholarly journals The Role of BMP Signaling in Osteoclast Regulation

2021 ◽  
Vol 9 (3) ◽  
pp. 24
Author(s):  
Brian Heubel ◽  
Anja Nohe
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Bone Diseases ◽  
Bmp Signaling ◽  
Bone Homeostasis ◽  
Direct Stimulation ◽  
Federal Drug Administration ◽  
Bmp Pathway ◽  
Stimulation Of

The osteogenic effects of Bone Morphogenetic Proteins (BMPs) were delineated in 1965 when Urist et al. showed that BMPs could induce ectopic bone formation. In subsequent decades, the effects of BMPs on bone formation and maintenance were established. BMPs induce proliferation in osteoprogenitor cells and increase mineralization activity in osteoblasts. The role of BMPs in bone homeostasis and repair led to the approval of BMP2 by the Federal Drug Administration (FDA) for anterior lumbar interbody fusion (ALIF) to increase the bone formation in the treated area. However, the use of BMP2 for treatment of degenerative bone diseases such as osteoporosis is still uncertain as patients treated with BMP2 results in the stimulation of not only osteoblast mineralization, but also osteoclast absorption, leading to early bone graft subsidence. The increase in absorption activity is the result of direct stimulation of osteoclasts by BMP2 working synergistically with the RANK signaling pathway. The dual effect of BMPs on bone resorption and mineralization highlights the essential role of BMP-signaling in bone homeostasis, making it a putative therapeutic target for diseases like osteoporosis. Before the BMP pathway can be utilized in the treatment of osteoporosis a better understanding of how BMP-signaling regulates osteoclasts must be established.

scholarly journals Bone health in spacefaring rodents and primates: systematic review and meta-analysis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jingyan Fu ◽  
Matthew Goldsmith ◽  
Sequoia D. Crooks ◽  
Sean F. Condon ◽  
Martin Morris ◽  
...  
Keyword(s):  
Bone Formation ◽  
Trabecular Bone ◽  
Bone Health ◽  
Volume Fraction ◽  
Meta Analysis ◽  
Bone Volume ◽  
Trabecular Bone Volume ◽  
Bone Volume Fraction ◽  
Percentage Difference ◽  
Induced Changes

AbstractAnimals in space exploration studies serve both as a model for human physiology and as a means to understand the physiological effects of microgravity. To quantify the microgravity-induced changes to bone health in animals, we systematically searched Medline, Embase, Web of Science, BIOSIS, and NASA Technical reports. We selected 40 papers focusing on the bone health of 95 rats, 61 mice, and 9 rhesus monkeys from 22 space missions. The percentage difference from ground control in rodents was –24.1% [Confidence interval: −43.4, −4.9] for trabecular bone volume fraction and –5.9% [−8.0, −3.8] for the cortical area. In primates, trabecular bone volume fraction was lower by –25.2% [−35.6, −14.7] in spaceflight animals compared to GC. Bone formation indices in rodent trabecular and cortical bone were significantly lower in microgravity. In contrast, osteoclast numbers were not affected in rats and were variably affected in mice. Thus, microgravity induces bone deficits in rodents and primates likely through the suppression of bone formation.

scholarly journals The Development of Molecular Biology of Osteoporosis

2021 ◽  
Vol 22 (15) ◽  
pp. 8182
Author(s):  
Yongguang Gao ◽  
Suryaji Patil ◽  
Jingxian Jia
Keyword(s):  
Bone Resorption ◽  
Molecular Biology ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Remodeling ◽  
Bone Cells ◽  
Cell Activity ◽  
Bone Cell ◽  
Bone Disorders ◽  
Molecular Aspects

Osteoporosis is one of the major bone disorders that affects both women and men, and causes bone deterioration and bone strength. Bone remodeling maintains bone mass and mineral homeostasis through the balanced action of osteoblasts and osteoclasts, which are responsible for bone formation and bone resorption, respectively. The imbalance in bone remodeling is known to be the main cause of osteoporosis. The imbalance can be the result of the action of various molecules produced by one bone cell that acts on other bone cells and influence cell activity. The understanding of the effect of these molecules on bone can help identify new targets and therapeutics to prevent and treat bone disorders. In this article, we have focused on molecules that are produced by osteoblasts, osteocytes, and osteoclasts and their mechanism of action on these cells. We have also summarized the different pharmacological osteoporosis treatments that target different molecular aspects of these bone cells to minimize osteoporosis.

Trabecular Bone is Increased in a Rat Model of Polycystic Ovary Syndrome

2020 ◽  
Author(s):  
Lady Katerine Serrano Mujica ◽  
Werner Giehl Glanzner ◽  
Amanda Luiza Prante ◽  
Vitor Braga Rissi ◽  
Gabrielle Rebeca Everling Correa ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Bone Formation ◽  
Type I Collagen ◽  
Polycystic Ovary ◽  
Osteoclast Differentiation ◽  
Bone Volume ◽  
Negative Regulator ◽  
Type I ◽  
Ovary Syndrome ◽  
The Impact

AbstractPolycystic ovary syndrome (PCOS) in an intricate disorder characterized by reproductive and metabolic abnormalities that may affect bone quality and strength along with the lifespan. The present study analysed the impact of postnatal androgenization (of a single dose of testosterone propionate 1.25 mg subcutaneously at day 5 of life) on bone development and markers of bone metabolism in adult female Wistar rats. Compared with healthy controls, the results of measurements of micro-computed tomography (microCT) of the distal femur of androgenized rats indicated an increased cortical bone volume voxel bone volume to total volume (VOX BV/TV) and higher trabecular number (Tb.n) with reduced trabecular separation (Tb.sp). A large magnitude effect size was observed in the levels of circulating bone formation Procollagen I N-terminal propeptide (P1NP) at day 60 of life; reabsorption cross-linked C-telopeptide of type I collagen (CTX) markers were similar between the androgenized and control rats at days 60 and 110 of life. The analysis of gene expression in bone indicated elements for an increased bone mass such as the reduction of the Dickkopf-1 factor (Dkk1) a negative regulator of osteoblast differentiation (bone formation) and the reduction of Interleukin 1-b (Il1b), an activator of osteoclast differentiation (bone reabsorption). Results from this study highlight the possible role of the developmental programming on bone microarchitecture with reference to young women with PCOS.

scholarly journals Bone Morphogenetic Proteins, Carriers, and Animal Models in the Development of Novel Bone Regenerative Therapies

Materials ◽  
2021 ◽  
Vol 14 (13) ◽  
pp. 3513
Author(s):  
Nikola Stokovic ◽  
Natalia Ivanjko ◽  
Drazen Maticic ◽  
Frank P. Luyten ◽  
Slobodan Vukicevic
Keyword(s):  
Animal Models ◽  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Animal Experiments ◽  
Inorganic Materials ◽  
New Bone Formation ◽  
Segmental Bone ◽  
Posterolateral Spinal Fusion ◽  
Regenerative Therapies ◽  
Observation Period

Bone morphogenetic proteins (BMPs) possess a unique ability to induce new bone formation. Numerous preclinical studies have been conducted to develop novel, BMP-based osteoinductive devices for the management of segmental bone defects and posterolateral spinal fusion (PLF). In these studies, BMPs were combined with a broad range of carriers (natural and synthetic polymers, inorganic materials, and their combinations) and tested in various models in mice, rats, rabbits, dogs, sheep, and non-human primates. In this review, we summarized bone regeneration strategies and animal models used for the initial, intermediate, and advanced evaluation of promising therapeutical solutions for new bone formation and repair. Moreover, in this review, we discuss basic aspects to be considered when planning animal experiments, including anatomical characteristics of the species used, appropriate BMP dosing, duration of the observation period, and sample size.

Absence of bone remodeling compartment canopies correlates with deficient bone formation in post-menopausal women

Bone ◽  
2010 ◽  
Vol 46 ◽  
pp. S67-S68
Author(s):  
Thomas Andersen ◽  
Ellen Hauge ◽  
Jens Bollerslev ◽  
Jean-Marie Delaisse
Keyword(s):  
Bone Formation ◽  
Bone Remodeling ◽  
Menopausal Women ◽  
Post Menopausal

Tissue-Level Mechanisms Responsible for the Increase in Bone Formation and Bone Volume by Sclerostin Antibody

2014 ◽  
Vol 29 (6) ◽  
pp. 1424-1430 ◽  
Author(s):  
Michael S Ominsky ◽  
Qing-Tian Niu ◽  
Chaoyang Li ◽  
Xiaodong Li ◽  
Hua Zhu Ke
Keyword(s):  
Bone Formation ◽  
Tissue Level ◽  
Bone Volume ◽  
Sclerostin Antibody

Regulation of bone repletion in rats subjected to varying low-calcium stress

1984 ◽  
Vol 246 (2) ◽  
pp. R190-R196 ◽  
Author(s):  
R. H. Drivdahl ◽  
C. C. Liu ◽  
D. J. Baylink
Keyword(s):  
Bone Formation ◽  
Formation Rate ◽  
Bone Volume ◽  
Strong Positive Correlation ◽  
Sprague Dawley ◽  
Bone Formation Rate ◽  
Osteoblast Activity ◽  
Calcium Stress ◽  
Sprague Dawley Rats ◽  
Very High

Weanling Sprague-Dawley rats subjected to varying degrees of low-Ca dietary stress (depletion) showed graded increases in the rate of endosteal bone formation when normal dietary Ca was restored (repletion). There was a strong positive correlation between the rate of bone resorption in depletion and the rate of bone formation attained after 1 wk of repletion. However, bone formation declined rapidly within the first 4 wk of repletion, despite the persistence of a substantial endosteal bone volume deficit. Furthermore the medullary area (indicative of bone volume) did not by itself determine the bone formation rate. Bone volume in test groups was restored to control levels after 6 mo of repletion, and this result could be predicted by a kinetic analysis. Thus, although very high rates of formation in early repletion decline rapidly, smaller increments relative to controls must be sustained for long periods. Our data indicate that increased formation rats at all stages of repletion are a consequence of elevations in both osteoblast number and osteoblast activity.

Effects of sialoadenectomy and exogenous EGF on molar drift and orthodontic tooth movement in rats

1994 ◽  
Vol 266 (5) ◽  
pp. E731-E738 ◽  
Author(s):  
C. Dolce ◽  
J. Anguita ◽  
L. Brinkley ◽  
P. Karnam ◽  
M. Humphreys-Beher ◽  
...  
Keyword(s):  
Bone Formation ◽  
Bone Remodeling ◽  
Alveolar Bone ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Alveolar Bone Remodeling ◽  
Tooth Roots ◽  
Epidermal Growth ◽  
Tetracycline Labeling ◽  
Distal Aspect

Effects on bone remodeling have been attributed to epidermal growth factor (EGF). Sialoadenectomy (SX) removes the major source of EGF in rodents and decreases both salivary and serum EGF levels. EGF effects on rat alveolar bone remodeling manifested by molar drift (MD) and orthodontic tooth movement (OTM) were examined using the following two approaches: 1) EGF depletion by SX and replacement by orally administered EGF (50 micrograms.animal-1.day-1); 2) sham rats supplemented with matching amounts of EGF. MD and OTM were measured using cephalometric radiographs; bone formation was measured histomorphometrically using tetracycline labeling. Normal MD was not detected after SX, and alveolar bone formation was significantly reduced both around the tooth and in nondental sites. Replacement EGF given to SX rats and supplemental EGF administered to sham rats changed the direction and enhanced the rate of MD. A mesially directed orthodontic force applied to the molars of SX animals increased bone formation on the distal aspect of the tooth roots. Supplemental EGF did not significantly affect OTM. EGF affects alveolar bone remodeling, as manifested clinically by alterations in normal maxillary MD.

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