scholarly journals Loss of Osteoblast Runx3 Produces Severe Congenital Osteopenia

2015 ◽  
Vol 35 (7) ◽  
pp. 1097-1109 ◽  
Author(s):  
Omri Bauer ◽  
Amnon Sharir ◽  
Ayako Kimura ◽  
Shay Hantisteanu ◽  
Shu Takeda ◽  
...  
Keyword(s):  
Bone Mineralization ◽  
Osteoblastic Cell ◽  
Human Infants ◽  
Bone Demineralization ◽  
Primary Osteoblast ◽  
Autonomous Function ◽  
Mineral Deposition ◽  
Signaling Components ◽  
Deficient Mice ◽  
Chromosome 1P36

Congenital osteopenia is a bone demineralization condition that is associated with elevated fracture risk in human infants. Here we show thatRunx3, likeRunx2, is expressed in precommitted embryonic osteoblasts and that Runx3-deficient mice develop severe congenital osteopenia. Runx3-deficient osteoblast-specific (Runx3fl/fl/Col1α1-cre), but not chondrocyte-specific (Runx3fl/fl/Col1α2-cre), mice are osteopenic. This demonstrates that an osteoblastic cell-autonomous function of Runx3 is required for proper osteogenesis. Bone histomorphometry revealed that decreased osteoblast numbers and reduced mineral deposition capacity in Runx3-deficient mice cause this bone formation deficiency. Neonatal bone and cultured primary osteoblast analyses revealed a Runx3-deficiency-associated decrease in the number of active osteoblasts resulting from diminished proliferation and not from enhanced osteoblast apoptosis. These findings are supported by Runx3-null culture transcriptome analyses showing significant decreases in the levels of osteoblastic markers and increases in the levels of Notch signaling components. Thus, while Runx2 is mandatory for the osteoblastic lineage commitment, Runx3 is nonredundantly required for the proliferation of these precommitted cells, to generate adequate numbers of active osteoblasts. HumanRUNX3resides on chromosome 1p36, a region that is associated with osteoporosis. Therefore, RUNX3 might also be involved in human bone mineralization.

Nanomechanics of Knockout Mouse Bones

2006 ◽  
Vol 975 ◽  
Author(s):  
N Beril Kavukcuoglu ◽  
Adrian B. Mann
Keyword(s):  
Mechanical Properties ◽  
Knockout Mice ◽  
Bone Mineralization ◽  
Bone Matrix ◽  
Wild Type ◽  
Knock Out ◽  
Bone Matrix Proteins ◽  
Fibrillin 1 ◽  
Deficient Mice ◽  
Radial Axis

ABSTRACTOsteocalcin (OC) and osteopontin (OPN) are among the most abundant non-collagenous bone matrix proteins. Both have drawn interest from investigators studying their function in osteoporosis and it is known that mutations of these proteins can also have dramatic effects on the properties of bone. Other proteins including fibrillin 1 and 2 (FBN2) have been less widely studied, but can be mutated in some individuals resulting in connective tissue disorders. It has been reported that abnormal fibrillin may play a role in decreased bone mass. In this study bones from osteopontin (OPN), osteocalcin (OC) and fibrillin-2 (FBN2) knockout mice have been investigated. The study has identified how these proteins affect the bone's nanomechanical properties (hardness and elastic modulus). Nanoindentation tests were performed on the radial axis of cortical femora bones from the knockout mice and their wildtype controls. The results showed that young (age< 12 weeks) OPN knock-out bones have significantly lower mechanical properties than wild-type bones indicate a crucial role for OPN in early bone mineralization. After 12 weeks of age, the OPN knockout and wild-type control bones did not show any statistical difference. In OC deficient mice the mechanical properties were found to increase in the cortical mid-shaft of femora from 1 year old mice, suggesting an increase in bone mineralization, but 3 month old FBN2 deficient mice bones showed a decrease in mechanical properties across the cortical radial axis of the mid- femora.

scholarly journals The effects of synthetic 19-norprogestins on osteoblastic cell function are mediated by their non-phenolic reduced metabolites

2007 ◽  
Vol 193 (3) ◽  
pp. 493-504 ◽  
Author(s):  
Juana Enríquez ◽  
Ana Elena Lemus ◽  
Jesús Chimal-Monroy ◽  
Higinio Arzate ◽  
Gustavo A García ◽  
...  
Keyword(s):  
Cell Function ◽  
Bone Cells ◽  
Neonatal Rat ◽  
Osteoblastic Cell ◽  
Osteoblast Proliferation ◽  
Mineral Deposition ◽  
Proliferation And Differentiation ◽  
Derivatives Of ◽  
Rat Osteoblasts

The key role of estrogens on osteoblastic cell function is well documented; however, the role of progesterone (P) and synthetic progestins remains controversial. While several reports indicate that P has no significant effects on bone cells, a number of clinical studies have shown that 19-norprogestins restore postmenopausal bone loss. The mechanisms by which 19-norprogestins induce estrogen-like effects on bone cells are not fully understood. To assess whether the actions of 19-norprogestins on osteoblasts are mediated by their non-phenolic metabolites, we studied the effects of norethisterone (NET), levonorgestrel (LNG), and two of their A-ring reduced derivatives upon cell proliferation and differentiation in neonatal rat osteoblasts. Osteoblast function was assessed by determining cell DNA, cell-associated osteocalcin and calcium content, alkaline phosphatase activity, and mineral deposition. P failed to induce changes on osteoblasts, while NET and LNG exerted a number of actions. The most striking finding was that the 3β,5α- and 3α,5α-tetrahydro derivatives of NET and LNG induced osteoblast proliferation and differentiation with higher potency than those exerted by their parent compounds, mimicking the effects of estradiol. Interestingly, osteoblast differentiation and mineral deposition induced by NET and LNG were abolished by finasteride, a 5α-reductases inhibitor, while the potent effect on osteoblast proliferation induced by progestin derivatives was abolished by a steroidal antiestrogen. Results demonstrate that A-ring reduced derivatives of NET and LNG exhibit intrinsic estrogen-like potency on rat osteoblasts, offering a plausible explanation for the mechanism of action of 19-norprogestins in bone restoration in postmenopausal women and providing new insights for hormone replacement therapy research.

Two-Armed Activation of Bone Mineral Deposition by the Flavones Baicalin and Baicalein, Encapsulated in Polyphosphate Microparticles

2017 ◽  
Vol 45 (03) ◽  
pp. 533-555 ◽  
Author(s):  
Xiao-Hong Wang ◽  
Yue-Wei Guo ◽  
Emad Tolba ◽  
Maria Kokkinopoulou ◽  
Matthias Wiens ◽  
...  
Keyword(s):  
Bone Mineralization ◽  
Osteoporosis Prevention ◽  
Calcium Efflux ◽  
Scutellaria Baicalensis Georgi ◽  
Calcium Polyphosphate ◽  
Mineral Deposition ◽  
Primary Human Osteoblasts ◽  
Intracellular Vesicles ◽  
New Applications ◽  
Hydroxyapatite Formation

In this study, we investigated the effect of the two flavonoids, baicalin (baicalein 7-O-[Formula: see text]- d-glucuronic acid) and its aglycone, baicalein (5,6,7-trihydroxyflavone), after encapsulation into amorphous calcium polyphosphate (Ca-polyP) microparticles on mineralization of primary human osteoblasts (phOSB). Both flavonoids, which come from root extracts of Scutellaria baicalensis Georgi, are used in Traditional Chinese Medicine, and are nontoxic in cells up to a concentration of 3[Formula: see text][Formula: see text]g/ml. The morphogenetically active, energy-rich Ca-polyP particles with a stoichiometric P:Ca ratio of 1:2 are degraded by cellular alkaline phosphatase (ALP) to ortho-phosphate used for bone hydroxyapatite formation. Here we show that the flavone-loaded Ca-polyP microparticles are readily taken up by phOSB, resulting in the accumulation of polyP around the nuclei and the formation of intracellular vesicles containing the ALP. In addition, we demonstrate that baicalin/baicalein causes a rise of the intracellular calcium [Ca[Formula: see text]]i a level which markedly is augmented after encapsulation into Ca-polyP, through activation of the phospholipase C. Moreover, both flavones, either alone or associated with Ca-polyP microparticles, upregulate the expression of the osteoblast calcium efflux channel, the plasma membrane Ca[Formula: see text]-ATPase (PMCA), while the expression of ALP, which promotes bone mineralization, is induced by Ca-polyP and by the flavones only if present in the Ca-polyP-microparticle-associated form. As a result, the extent of bone mineralization is markedly enhanced. Based on the two-armed activating function, new applications of baicalin/baicalein as a component of nutriceuticals for osteoporosis prevention or bone implants can be envisaged.

scholarly journals Increased Osteopontin Contributes to Inhibition of Bone Mineralization in FGF23-Deficient Mice

2014 ◽  
Vol 29 (3) ◽  
pp. 693-704 ◽  
Author(s):  
Quan Yuan ◽  
Yan Jiang ◽  
Xuefeng Zhao ◽  
Tadatoshi Sato ◽  
Michael Densmore ◽  
...  
Keyword(s):  
Bone Mineralization ◽  
Deficient Mice

scholarly journals Altered distribution of bone matrix proteins and defective bone mineralization in klotho-deficient mice

Bone ◽  
2013 ◽  
Vol 57 (1) ◽  
pp. 206-219 ◽  
Author(s):  
Muneteru Sasaki ◽  
Tomoka Hasegawa ◽  
Tamaki Yamada ◽  
Hiromi Hongo ◽  
Paulo Henrique Luiz de Freitas ◽  
...  
Keyword(s):  
Bone Mineralization ◽  
Bone Matrix ◽  
Matrix Proteins ◽  
Bone Matrix Proteins ◽  
Defective Bone ◽  
Deficient Mice

scholarly journals The Optical Coherence Tomography and Raman Spectroscopy for Sensing of the Bone Demineralization Process

Sensors ◽  
2021 ◽  
Vol 21 (19) ◽  
pp. 6468
Author(s):  
Maciej J. Głowacki ◽  
Aleksandra M. Kamińska ◽  
Marcin Gnyba ◽  
Jerzy Pluciński ◽  
Marcin R. Strąkowski
Keyword(s):  
Raman Spectroscopy ◽  
Optical Coherence Tomography ◽  
Bone Mineralization ◽  
Optical Methods ◽  
Optical Coherence ◽  
Bone Demineralization ◽  
Raman Measurement ◽  
Preliminary Study ◽  
Optical Examination ◽  
Bone Condition

The presented research was intended to seek new optical methods to investigate the demineralization process of bones. Optical examination of the bone condition could facilitate clinical trials and improve the safety of patients. The authors used a set of complementary methods: polarization-sensitive optical coherence tomography (PS-OCT) and Raman spectroscopy. Chicken bone samples were used in this research. To stimulate in laboratory conditions the process of demineralization and gradual removal of the hydroxyapatite, the test samples of bones were placed into 10% acetic acid. Measurements were carried out in two series. The first one took two weeks with data acquired every day. In the second series, the measurements were made during one day at an hourly interval (after 1, 2, 3, 5, 7, 10, and 24 h). The relation between the content of hydroxyapatite and images recorded using OCT was analyzed and discussed. Moreover, the polarization properties of the bones, including retardation angles of the bones, were evaluated. Raman measurement confirmed the disappearance of the hydroxyapatite and the speed of this process. This work presents the results of the preliminary study on the possibility of measuring changes in bone mineralization by means of the proposed methods and confirms their potential for practical use in the future.

Effect of Physical Activity on Skeletal Integrity and its Implications for Calcium Requirement Studies

1987 ◽  
Vol 5 (1-2) ◽  
pp. 53-60
Author(s):  
Brian J. Westrich
Keyword(s):  
Physical Activity ◽  
General Population ◽  
Bone Mineralization ◽  
Primary Role ◽  
Activity Profile ◽  
Bone Demineralization ◽  
Calcium Requirement ◽  
Prevention Of Osteoporosis ◽  
Skeletal Integrity

A major task confronting those who establish calcium recommendations is the determination of a minimum level of calcium intake that will promote bone mineralization and/or reduce bone demineralization sufficiently to aid in the prevention of osteoporosis. The evidence reviewed here indicates that physical activity plays a primary role in the maintenance of skeletal integrity. Thus, to obtain data on calcium recommendations that are relevant to the general population, it is essential that calcium requirement studies use subjects whose physical activity profile is representative of the general population. Of all the factors known to shift the [bone] remodeling process in favor of formation, perhaps the most important, after growth, is mechanical stress… Heaney (1982)

scholarly journals Histological and elemental analyses of impaired bone mineralization in klotho-deficient mice

2008 ◽  
Vol 212 (3) ◽  
pp. 275-285 ◽  
Author(s):  
Hironobu Suzuki ◽  
Norio Amizuka ◽  
Kimimitsu Oda ◽  
Masaki Noda ◽  
Hayato Ohshima ◽  
...  
Keyword(s):  
Bone Mineralization ◽  
Elemental Analyses ◽  
Deficient Mice

scholarly journals Lgr6 marks nail stem cells and is required for digit tip regeneration

2015 ◽  
Vol 112 (43) ◽  
pp. 13249-13254 ◽  
Author(s):  
Jessica A. Lehoczky ◽  
Clifford J. Tabin
Keyword(s):  
Stem Cells ◽  
Nail Plate ◽  
Sweat Glands ◽  
Genetic Lineage ◽  
Human Infants ◽  
Direct Role ◽  
Stem Cell Populations ◽  
G Protein Coupled ◽  
Deficient Mice ◽  
Eccrine Sweat Glands

The tips of the digits of some mammals, including human infants and mice, are capable of complete regeneration after injury. This process is reliant on the presence of the overlaying nail organ and is mediated by a proliferative blastema. Epithelial Wnt/β-catenin signaling has been shown to be necessary for mouse digit tip regeneration. Here, we report on Lgr5 and Lgr6 (leucine-rich repeat-containing G protein-coupled receptor 5 and 6), two important agonists of the Wnt pathway that are known to be markers of several epithelial stem cell populations. We find that Lgr5 is expressed in a dermal population of cells adjacent to the specialized epithelia surrounding the keratinized nail plate. Moreover, Lgr5-expressing cells contribute to this dermis, but not the blastema, during digit tip regeneration. In contrast, we find that Lgr6 is expressed within cells of the nail matrix portion of the nail epithelium, as well as in a subset of cells in the bone and eccrine sweat glands. Genetic lineage analysis reveals that Lgr6-expressing cells give rise to the nail during homeostatic growth, demonstrating that Lgr6 is a marker of nail stem cells. Moreover, Lgr6-expressing cells contribute to the blastema, suggesting a potential direct role for Lgr6-expressing cells during digit tip regeneration. This role is confirmed by analysis of Lgr6-deficient mice, which have both a nail and bone regeneration defect.

Abstract 210: Liver Expression of Proinflammatory Cytokines in Adiponectin Deficient Mice

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Arshi Jha ◽  
Esther Yu ◽  
Jayabala Pamidimukkala
Keyword(s):  
Angiotensin Ii ◽  
Proinflammatory Cytokines ◽  
Liver Tissue ◽  
Tissue Expression ◽  
Inflammatory Conditions ◽  
Dose Infusion ◽  
Chronic Infusion ◽  
Signaling Components ◽  
Deficient Mice

Adiponectin is one of the few peptides secreted by fat known to have anti-inflammatory properties. Obesity in humans is associated with low levels of circulating adiponectin. Adiponectin deficiency could potentially lead to a proinflammatory milieu, increasing susceptibility to progression of cardiovascular diseases and other inflammatory conditions. Previous studies from our lab have shown that adiponectin deficiency in mice did not lead to statistically significant increases in circulating levels of proinflammatory cytokines under basal conditions or in response to low dose infusion of Angiotensin II (ANGII). The present study evaluates the effect of chronic ANGII infusion on expression of cytokines in the livers of female C57BL/6J and adiponectin deficient mice (Adipo -/-). Female mice (24-28wks), were implanted with osmotic pump containing either ANG II (800 ng/Kg /min) or saline. Blood samples and tissue were collected at the end of 14 days. Liver tissue expression of the cytokines were quantified using real-time PCR (BioRad CFX 96 thermocycler) and SYBR Green mastermix. Data was normalized to the expression of GAPDH. Expression of cytokines IL6, IL8, IL17a was undetectable in the liver tissue of C57BL/6J and Adiponectin deficient mice. Angiotensin II infusion did not produce detectable changes in cytokine expression in either group. Expression of TNFα, TGF β , and adhesion molecules such as E-Selectin, VCAM1, Collagen1a1 in Adipo-/- mice were comparable to that of C57BL/6J mice. ANGII infusion did not produce statistically significant changes in these biomarkers either. Finally, expression of ANGII signaling components such as Angiotensin type 1 receptor (AT 1 ), NFκB and PPARγ were robustly expressed in both C57BL/6J and adiponectin deficient mice. In conclusion, chronic infusion of ANGII in Adiponectin deficiency did not result in a significant increases in expression of markers of proinflammatory milieu in the liver tissue.

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