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Article ; Online: Aromatase deficiency in transplanted bone marrow cells improves vertebral trabecular bone quantity, connectivity, and mineralization and decreases cortical porosity in murine bone marrow transplant recipients.

Rubitschung, Katie / Sherwood, Amber / Kapadia, Rasesh / Xi, Yin / Hajibeigi, Asghar / Rubinow, Katya B / Zerwekh, Joseph E / Öz, Orhan K

PloS one

2024 Volume 19, Issue 2, Page(s) e0296390

Abstract: Estradiol is an important regulator of bone accumulation and maintenance. Circulating estrogens are primarily produced by the gonads. Aromatase, the enzyme responsible for the conversion of androgens to estrogen, is expressed by bone marrow cells (BMCs) ... ...

Abstract	Estradiol is an important regulator of bone accumulation and maintenance. Circulating estrogens are primarily produced by the gonads. Aromatase, the enzyme responsible for the conversion of androgens to estrogen, is expressed by bone marrow cells (BMCs) of both hematopoietic and nonhematopoietic origin. While the significance of gonad-derived estradiol to bone health has been investigated, there is limited understanding regarding the relative contribution of BMC derived estrogens to bone metabolism. To elucidate the role of BMC derived estrogens in male bone, irradiated wild-type C57BL/6J mice received bone marrow cells transplanted from either WT (WT(WT)) or aromatase-deficient (WT(ArKO)) mice. MicroCT was acquired on lumbar vertebra to assess bone quantity and quality. WT(ArKO) animals had greater trabecular bone volume (BV/TV p = 0.002), with a higher trabecular number (p = 0.008), connectivity density (p = 0.017), and bone mineral content (p = 0.004). In cortical bone, WT(ArKO) animals exhibited smaller cortical pores and lower cortical porosity (p = 0.02). Static histomorphometry revealed fewer osteoclasts per bone surface (Oc.S/BS%), osteoclasts on the erosion surface (ES(Oc+)/BS, p = 0.04) and low number of osteoclasts per bone perimeter (N.Oc/B.Pm, p = 0.01) in WT(ArKO). Osteoblast-associated parameters in WT(ArKO) were lower but not statistically different from WT(WT). Dynamic histomorphometry suggested similar bone formation indices' patterns with lower mean values in mineral apposition rate, label separation, and BFR/BS in WT(ArKO) animals. Ex vivo bone cell differentiation assays demonstrated relative decreased osteoblast differentiation and ability to form mineralized nodules. This study demonstrates a role of local 17β-estradiol production by BMCs for regulating the quantity and quality of bone in male mice. Underlying in vivo cellular and molecular mechanisms require further study.
MeSH term(s)	Mice ; Animals ; Male ; Aromatase/genetics ; Aromatase/metabolism ; Bone Marrow Transplantation ; Cancellous Bone/diagnostic imaging ; Cancellous Bone/metabolism ; Porosity ; Mice, Inbred C57BL ; Estrogens ; Estradiol ; Bone Marrow Cells/metabolism ; Spine/metabolism ; Mice, Knockout ; Gynecomastia ; Infertility, Male ; Metabolism, Inborn Errors ; 46, XX Disorders of Sex Development
Chemical Substances	Aromatase (EC 1.14.14.1) ; Estrogens ; Estradiol (4TI98Z838E)
Language	English
Publishing date	2024-02-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0296390
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Article ; Online: Bone disease and hypercalciuria in children.

Zerwekh, Joseph E

Pediatric nephrology (Berlin, Germany)

2009 Volume 25, Issue 3, Page(s) 395–401

Abstract: There have been relatively few studies of bone mass in children with idiopathic hypercalciuria (IH). When performed, bone mineral density (BMD) measurements have consistently disclosed decreased Z-scores for children with IH at the lumbar spine and, to a ...

Abstract	There have been relatively few studies of bone mass in children with idiopathic hypercalciuria (IH). When performed, bone mineral density (BMD) measurements have consistently disclosed decreased Z-scores for children with IH at the lumbar spine and, to a lesser extent, at the femoral neck. Few investigations have delineated the nature of the mechanism(s) that may contribute to the bone loss in these children. Some studies have been consistent, showing increased bone resorption as the probable mechanism of bone loss. To date, there have been no reports regarding the assessment of biochemical markers specific for bone formation in children with IH. However, since most of the children with IH in these reports had demonstrated normal longitudinal growth, it seems less likely that there is an alteration in bone formation. The causes for increased bone resorption also are not firmly established, but genetics, dietary indiscretions, and altered cytokine production have been proposed as being contributory to the decreased BMD observed in these children with IH. Optimal bone mineral accretion during childhood and adolescence is important in attaining peak bone mass and may serve to prevent the development of osteoporosis in adulthood. Thus, a better understanding of bone loss in children with IH is warranted.
MeSH term(s)	Bone Density/physiology ; Bone Development/physiology ; Bone Diseases/complications ; Bone Diseases/pathology ; Bone Resorption/pathology ; Child ; Humans ; Hypercalciuria/complications ; Hypercalciuria/pathology ; Organ Size/physiology
Language	English
Publishing date	2009-11-03
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	631932-4
ISSN	1432-198X ; 0931-041X
ISSN (online)	1432-198X
ISSN	0931-041X
DOI	10.1007/s00467-009-1338-z
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Article: Bone disease and idiopathic hypercalciuria.

Zerwekh, Joseph E

Seminars in nephrology

2008 Volume 28, Issue 2, Page(s) 133–142

Abstract: Observational and epidemiologic studies alike have shown that idiopathic hypercalciuric (IH) stone-forming patients typically show bone mineral density scores that are significantly lower than those observed for age- and sex-matched normal subjects or ... ...

Abstract	Observational and epidemiologic studies alike have shown that idiopathic hypercalciuric (IH) stone-forming patients typically show bone mineral density scores that are significantly lower than those observed for age- and sex-matched normal subjects or those for nonhypercalciuric stone-forming patients. Most of these studies have relied on changes in bone mineral density and have not explored the mechanism(s) involved. There have been a small number of studies that have relied on dynamic bone histomorphometry to ascertain the nature of the bone defect in IH patients. When performed, these studies clearly have shown increased bone resorption and high bone turnover in patients with fasting hypercalciuria whereas suppressed bone formation indices are the most consistent finding in patients with the absorptive variant of IH. The causes of this apparent difference in bone remodeling between the 2 variants of IH still is uncertain. Available evidence suggests that potential mechanisms may be dependent in large part to genetic, metabolic, and nutritional causes of hypercalciuria and bone loss in patients with IH.
MeSH term(s)	Bone Density ; Bone Diseases, Metabolic/etiology ; Bone Remodeling ; Bone Resorption ; Diet/adverse effects ; Humans ; Hypercalciuria/complications ; Hypercalciuria/physiopathology ; Urolithiasis/physiopathology ; Urolithiasis/urine
Language	English
Publishing date	2008-03-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	604652-6
ISSN	1558-4488 ; 0270-9295
ISSN (online)	1558-4488
ISSN	0270-9295
DOI	10.1016/j.semnephrol.2008.01.006
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Article ; Online: Blood biomarkers of vitamin D status.

Zerwekh, Joseph E

The American journal of clinical nutrition

2007 Volume 87, Issue 4, Page(s) 1087S–91S

Abstract: In the past quarter century, more than 50 metabolites of vitamin D have been described. To date, only a few of these have been quantified in blood, but this has widened our understanding of the pathologic role that altered vitamin D metabolism plays in ... ...

Abstract	In the past quarter century, more than 50 metabolites of vitamin D have been described. To date, only a few of these have been quantified in blood, but this has widened our understanding of the pathologic role that altered vitamin D metabolism plays in the development of diseases of calcium homeostasis. Currently, awareness is growing of the prevalence of vitamin D insufficiency in the general population in association with an increased risk of several diseases. However, for many researchers, it is not clear which vitamin D metabolites should be quantified and what the information gained from such an analysis tells us. Only 2 metabolites, namely, 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D], have received the greatest attention. Of these, the need for measuring serum 1,25(OH)2D is limited, and this metabolite should therefore not be considered as part of the standard vitamin D testing regimen. On the other hand, serum 25(OH)D provides the single best assessment of vitamin D status and thus should be the only vitamin D assay typically performed. Currently, numerous formats exist for measuring serum 25(OH)D concentrations, each with its own advantages and disadvantages. This article reviews the currently available methods for serum 25(OH)D quantitation and considers important issues such as whether both the D2 and the D3 forms of the vitamin should be assayed, whether total or free concentrations are most important, and what measures should be taken to ensure the fidelity of the measurements.
MeSH term(s)	Biomarkers/blood ; Blood Chemical Analysis ; Bone Density Conservation Agents ; Calcium/metabolism ; Cholecalciferol/blood ; Clinical Laboratory Techniques ; Ergocalciferols/blood ; Humans ; Nutrition Assessment ; Nutritional Status ; Vitamin D/analogs & derivatives ; Vitamin D/analysis ; Vitamin D/blood
Chemical Substances	Biomarkers ; Bone Density Conservation Agents ; Ergocalciferols ; Vitamin D (1406-16-2) ; Cholecalciferol (1C6V77QF41) ; 25-hydroxyvitamin D (A288AR3C9H) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2007-04-18
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	280048-2
ISSN	1938-3207 ; 0002-9165
ISSN (online)	1938-3207
ISSN	0002-9165
DOI	10.1093/ajcn/87.4.1087S
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Article: The measurement of vitamin D: analytical aspects.

Zerwekh, Joseph E

Annals of clinical biochemistry

2004 Volume 41, Issue Pt 4, Page(s) 272–281

Abstract: In the past quarter of a century, our understanding of the metabolism and mechanism of action of vitamin D has been elucidated. During this period, many metabolites of vitamin D have been identified and a small proportion of these assayed in blood. The ... ...

Abstract	In the past quarter of a century, our understanding of the metabolism and mechanism of action of vitamin D has been elucidated. During this period, many metabolites of vitamin D have been identified and a small proportion of these assayed in blood. The ability to assay these vitamin D metabolites has led to a better appreciation of the pathological role that altered vitamin D metabolism plays in the development of diseases of calcium homeostasis. However, for many physicians it is not clear which vitamin D metabolites should be quantitated and what the information gained tells us. Of the four major circulating vitamin D metabolites in blood, only two, namely 25-hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D [1,25(OH)(2)D], have warranted measurement. Of these, the need for assessing serum 1,25(OH)(2)D is actually quite limited and should therefore not be considered as part of the standard vitamin D testing regimen. 25OHD, on the other hand, provides us with the single best assessment of vitamin D nutritional status and should be the only vitamin D assay typically ordered for this reason. Which of the many methods that are available should a laboratory use for quantitating either of these vitamin D metabolites? Early methods required large volumes of blood, organic solvent extractions, and extensive purification of the vitamin D metabolites prior to assay. Today, these time-consuming and costly methods have given way to a range of radioimmunoassays and enzyme-linked immunosorbent assays that can accurately and conveniently provide important information concerning an individual's vitamin D status. This review will consider when vitamin D measurements should be undertaken and how best to perform such assays.
MeSH term(s)	Blood Chemical Analysis/methods ; Blood Chemical Analysis/statistics & numerical data ; Calcitriol/analysis ; Chemistry Techniques, Analytical/methods ; Humans ; Vitamin D/analogs & derivatives ; Vitamin D/analysis ; Vitamin D/blood ; Vitamin D/metabolism
Chemical Substances	Vitamin D (1406-16-2) ; 25-hydroxyvitamin D (A288AR3C9H) ; Calcitriol (FXC9231JVH)
Language	English
Publishing date	2004-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	390309-6
ISSN	1758-1001 ; 0004-5632
ISSN (online)	1758-1001
ISSN	0004-5632
DOI	10.1258/0004563041201464
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Article: Blood biomarkers of vitamin D status

Zerwekh, Joseph E

American journal of clinical nutrition AJN. 2008 Apr., v. 87, no. 4

2008

Abstract	In the past quarter century, more than 50 metabolites of vitamin D have been described. To date, only a few of these have been quantified in blood, but this has widened our understanding of the pathologic role that altered vitamin D metabolism plays in the development of diseases of calcium homeostasis. Currently, awareness is growing of the prevalence of vitamin D insufficiency in the general population in association with an increased risk of several diseases. However, for many researchers, it is not clear which vitamin D metabolites should be quantified and what the information gained from such an analysis tells us. Only 2 metabolites, namely, 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)₂D], have received the greatest attention. Of these, the need for measuring serum 1,25(OH)₂D is limited, and this metabolite should therefore not be considered as part of the standard vitamin D testing regimen. On the other hand, serum 25(OH)D provides the single best assessment of vitamin D status and thus should be the only vitamin D assay typically performed. Currently, numerous formats exist for measuring serum 25(OH)D concentrations, each with its own advantages and disadvantages. This article reviews the currently available methods for serum 25(OH)D quantitation and considers important issues such as whether both the D₂ and the D₃ forms of the vitamin should be assayed, whether total or free concentrations are most important, and what measures should be taken to ensure the fidelity of the measurements.
Keywords	vitamin D ; biomarkers ; nutrient reserves ; nutrition assessment ; nutritional status ; blood chemistry ; humans ; vitamin metabolism ; metabolites ; 25-hydroxycholecalciferol ; 25-hydroxyergocalciferol ; calcitriol
Language	English
Dates of publication	2008-04
Size	p. 1087S-1091S.
Publishing place	American Society for Nutrition
Document type	Article
Note	In the special section: Assessment of vitamin D in population-based studies / edited by A.E. Millen, L.M. Bodnar, and M.F. Holick. Proceeding of a symposium held on May 1, 2007, in Washington, DC.
ZDB-ID	280048-2
ISSN	1938-3207 ; 0002-9165
ISSN (online)	1938-3207
ISSN	0002-9165
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Article: Nutrition and renal stone disease in space.

Zerwekh, Joseph E

Nutrition (Burbank, Los Angeles County, Calif.)

2002 Volume 18, Issue 10, Page(s) 857–863

Abstract: There is a growing body of evidence from the National Aeronautics and Space Administration and the Russian space program showing that humans exposed to the microgravity environment of space have a greater risk for developing renal stones. Increased bone ... ...

Abstract	There is a growing body of evidence from the National Aeronautics and Space Administration and the Russian space program showing that humans exposed to the microgravity environment of space have a greater risk for developing renal stones. Increased bone resorption and the attendant hypercalciuria and hyperphosphaturia contribute significantly to raising the urinary state of saturation with respect to the calcium salts, namely calcium oxalate and calcium phosphate. In addition, other environmental and dietary factors may adversely affect urine composition and increase stone formation risk during space flight. For example, reductions in urinary volume, pH, and citrate contribute to raising stone formation risk. In addition to raising the risk for calcium stone formation, this metabolic profile is conducive to the formation of uric acid stones. Although observations to date have suggested that there may actually be a reduced food intake during the early phase of flight, crew members on longer-duration flights may increase food intake and be at increased risk for stone formation. Taken together, these findings support the use of nutritional recommendations for crew members that would serve to reduce the stone-forming propensity of the urinary environment. Pharmacologic intervention should be directed at raising urinary volumes, diminishing bone losses, and preventing reductions in urinary pH and citrate. Success in reducing the risk for stone formation in astronauts would also be of potential major benefit to the estimated 20 million Americans with nephrolithiasis.
MeSH term(s)	Aerospace Medicine ; Calcium/urine ; Diet ; Humans ; Kidney Calculi/etiology ; Kidney Calculi/prevention & control ; Phosphates/urine ; Risk Factors ; Space Flight ; USSR ; United States ; United States National Aeronautics and Space Administration ; Weightlessness/adverse effects ; Weightlessness Countermeasures
Chemical Substances	Phosphates ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2002-07-10
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	639259-3
ISSN	1873-1244 ; 0899-9007
ISSN (online)	1873-1244
ISSN	0899-9007
DOI	10.1016/s0899-9007(02)00911-5
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Article: Estrogen and androgen play distinct roles in bone turnover in male mice before and after reaching sexual maturity.

Zerwekh, Joseph E / Oz, Orhan K

Bone

2007 Volume 40, Issue 2, Page(s) 553

MeSH term(s)	Androgens/physiology ; Animals ; Aromatase/genetics ; Aromatase/physiology ; Bone Density ; Bone and Bones/physiology ; Estrogens/physiology ; Male ; Mice ; Mice, Knockout ; Orchiectomy ; Osteogenesis/physiology ; Sexual Maturation
Chemical Substances	Androgens ; Estrogens ; Aromatase (EC 1.14.14.1)
Language	English
Publishing date	2007-02
Publishing country	United States
Document type	Comment ; Letter
ZDB-ID	632515-4
ISSN	1873-2763 ; 8756-3282
ISSN (online)	1873-2763
ISSN	8756-3282
DOI	10.1016/j.bone.2006.08.014
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Article ; Online: Unusual mid-shaft fractures during long-term bisphosphonate therapy.

Odvina, Clarita V / Levy, Shiri / Rao, Sudhir / Zerwekh, Joseph E / Rao, D S

Clinical endocrinology

2010 Volume 72, Issue 2, Page(s) 161–168

Abstract: Background: Bisphosphonates are the most commonly prescribed medications for the treatment of osteoporosis. Although existing evidence supports a good safety profile, there is concern that chronic administration of these agents could result in severe ... ...

Abstract	Background: Bisphosphonates are the most commonly prescribed medications for the treatment of osteoporosis. Although existing evidence supports a good safety profile, there is concern that chronic administration of these agents could result in severe suppression of bone turnover with increased risk of nonvertebral fractures. Objective: The objective of this study was to report the clinical presentation, selected bone histomorphometry and X-ray images of patients who developed mid-shaft long bone fractures during bisphosphonate therapy, six of whom had bone biopsy for histomorphometery. Results: Of the 13 patients who sustained atraumatic mid-shaft fractures, 10 were on alendronate and three were on risedronate therapy before the fractures. In addition to bisphosphonates, three patients were on oestrogen and two on tamoxifen concomitantly. Four patients with glucocorticoid-induced osteoporosis were on alendronate for 3-11 years along with glucocorticoid therapy. Bone histomorphometry showed severe suppression of bone turnover in five patients and low bone turnover in one patient. Conclusion: Long-term bisphosphonate therapy may increase the risk of unusual long bone mid-shaft fractures. This is probably due to prolonged suppression of bone turnover, which could lead to accumulation of microdamage and development of hypermineralized bone. At present, the scope of this complication in the larger context of patients receiving bisphosphonate therapy remains unknown, but appears to be small.
MeSH term(s)	Adult ; Aged ; Alendronate/adverse effects ; Alendronate/pharmacology ; Alendronate/therapeutic use ; Bone Density Conservation Agents/adverse effects ; Bone Density Conservation Agents/pharmacology ; Bone Density Conservation Agents/therapeutic use ; Bone and Bones/drug effects ; Diphosphonates/adverse effects ; Diphosphonates/pharmacology ; Diphosphonates/therapeutic use ; Etidronic Acid/adverse effects ; Etidronic Acid/analogs & derivatives ; Etidronic Acid/pharmacology ; Etidronic Acid/therapeutic use ; Female ; Fractures, Bone/chemically induced ; Humans ; Middle Aged ; Osteoporosis/drug therapy ; Risedronate Sodium
Chemical Substances	Bone Density Conservation Agents ; Diphosphonates ; Etidronic Acid (M2F465ROXU) ; Risedronate Sodium (OFG5EXG60L) ; Alendronate (X1J18R4W8P)
Language	English
Publishing date	2010-02
Publishing country	England
Document type	Journal Article
ZDB-ID	121745-8
ISSN	1365-2265 ; 0300-0664
ISSN (online)	1365-2265
ISSN	0300-0664
DOI	10.1111/j.1365-2265.2009.03581.x
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Article ; Online: Inhibition of osteoclast formation and function by bicarbonate: role of soluble adenylyl cyclase.

Geng, Weidong / Hill, Kathy / Zerwekh, Joseph E / Kohler, Thomas / Müller, Ralph / Moe, Orson W

Journal of cellular physiology

2009 Volume 220, Issue 2, Page(s) 332–340

Abstract: High [HCO(3)(-)] inhibits and low [HCO(3)(-)] stimulates bone resorption, which mediates part of the effect of chronic acidosis or acid feeding on bone. Soluble adenylyl cyclase (sAC) is a bicarbonate sensor that can potentially mediate the effect of ... ...

Abstract	High [HCO(3)(-)] inhibits and low [HCO(3)(-)] stimulates bone resorption, which mediates part of the effect of chronic acidosis or acid feeding on bone. Soluble adenylyl cyclase (sAC) is a bicarbonate sensor that can potentially mediate the effect of bicarbonate on osteoclasts. Osteoclasts were incubated in 0, 12, and 24 mM HCO(3)(-) at pH 7.4 for 7-8 days and assayed for tartrate-resistant acid phosphatase (TRAP) and vacuolar-ATPase expression, and H+ accumulation. Total number and area of TRAP (+) multinucleated osteoclasts was decreased by HCO(3)(-) in a dose-dependent manner. V-ATPase expression and H+ accumulation normalized to cell cross-sectional area or protein were not significantly changed. The HCO(3)(-) -induced inhibition of osteoclast growth and differentiation was blocked by either 2-hydroxyestradiol, an inhibitor of sAC or sAC knockdown by sAC specific siRNA. The model of HCO(3)(-) inhibiting osteoclast via sAC was further supported by the fact that the HCO(3)(-) dose-response on osteoclasts is flat when cells were saturated with 8-bromo-cAMP, a permeant cAMP analog downstream from sAC thus simulating sAC activation. To confirm our in vitro findings in intact bone, we developed a 1-week mouse calvaria culture system where osteoclasts were shown to be viable. Bone volume density (BV/TV) determined by micro-computed tomography (microCT), was higher in 24 mM HCO(3)(-) compared to 12 mM HCO(3)(-) treated calvaria. This HCO(3)(-) effect on BV/TV was blocked by 2-hydroxyestradiol. In summary, sAC mediates the inhibition of osteoclast function by HCO(3)(-), by acting as a HCO(3)(-) sensor.
MeSH term(s)	8-Bromo Cyclic Adenosine Monophosphate/metabolism ; Acid Phosphatase/metabolism ; Adenylyl Cyclases/pharmacology ; Animals ; Bicarbonates/pharmacology ; Cell Differentiation/drug effects ; Cell Differentiation/physiology ; Cell Line ; Cells, Cultured ; Estradiol/analogs & derivatives ; Estradiol/pharmacology ; Female ; Humans ; Isoenzymes/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Osteoclasts/cytology ; Osteoclasts/drug effects ; Osteoclasts/physiology ; Protons ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Skull/cytology ; Skull/drug effects ; Skull/metabolism ; Tartrate-Resistant Acid Phosphatase ; Vacuolar Proton-Translocating ATPases/metabolism
Chemical Substances	Bicarbonates ; Isoenzymes ; Protons ; RNA, Small Interfering ; 8-Bromo Cyclic Adenosine Monophosphate (23583-48-4) ; Estradiol (4TI98Z838E) ; 2-hydroxyestradiol (AYU2L67YUU) ; Acid Phosphatase (EC 3.1.3.2) ; Acp5 protein, mouse (EC 3.1.3.2) ; Tartrate-Resistant Acid Phosphatase (EC 3.1.3.2) ; Vacuolar Proton-Translocating ATPases (EC 3.6.1.-) ; Adenylyl Cyclases (EC 4.6.1.1)
Language	English
Publishing date	2009-04-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3116-1
ISSN	1097-4652 ; 0021-9541
ISSN (online)	1097-4652
ISSN	0021-9541
DOI	10.1002/jcp.21767
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