C-type Natriuretic Peptide Increases Bone Resorption in 1,25-Dihydroxyvitamin D3-stimulated Mouse Bone Marrow Cultures

Holliday, L. Shannon; Dean, Alan D.; Greenwald, James E.; Gluck, Stephen L.

doi:10.1074/jbc.270.32.18983

Cited by 64 publications

(72 citation statements)

References 39 publications

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“…Immunoprecipitation and Immunoblots-Osteoclasts were generated from primary mouse marrow cultures as previously described (24). RAW 264 cells were cultured in RPMI medium (Life Technologies, Inc.) containing 10% fetal calf serum (Life Technologies) and osteoprotegerin ligand (Sigma).…”

Section: Methodsmentioning

confidence: 99%

Interaction between Aldolase and Vacuolar H+-ATPase

Lu¹,

Holliday²,

Zhang³

et al. 2001

Journal of Biological Chemistry

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173

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Vacuolar H؉ -ATPases (V-ATPases) are essential for acidification of intracellular compartments and for proton secretion from the plasma membrane in kidney epithelial cells and osteoclasts. The cellular proteins that regulate V-ATPases remain largely unknown. A screen for proteins that bind the V-ATPase E subunit using the yeast two-hybrid assay identified the cDNA clone coded for aldolase, an enzyme of the glycolytic pathway. The interaction between E subunit and aldolase was confirmed in vitro by precipitation assays using E subunit-glutathione S-transferase chimeric fusion proteins and metabolically labeled aldolase. Aldolase was isolated associated with intact V-ATPase from bovine kidney microsomes and osteoclast-containing mouse marrow cultures in co-immunoprecipitation studies performed using an anti-E subunit monoclonal antibody. The interaction was not affected by incubation with aldolase substrates or products. In immunocytochemical assays, aldolase was found to colocalize with V-ATPase in the renal proximal tubule. In osteoclasts, the aldolase-V-ATPase complex appeared to undergo a subcellular redistribution from perinuclear compartments to the ruffled membranes following activation of resorption. In yeast cells deficient in aldolase, the peripheral V 1 domain of V-ATPase was found to dissociate from the integral membrane V 0 domain, indicating direct coupling of glycolysis to the proton pump. The direct binding interaction between V-ATPase and aldolase may be a new mechanism for the regulation of the V-ATPase and may underlie the proximal tubule acidification defect in hereditary fructose intolerance. Vacuolar Hϩ -ATPases (V-ATPases) 1 are large multisubunit proteins that are evolutionarily related and structurally similar to the F-ATPases (for a review, see Ref. 1). V-ATPases function in the acidification of a variety of intracellular compartments in eukaryotic cells (2) and in proton secretion from the plasma membrane of some specialized cells in higher organisms (3, 4). V-ATPases are required for maintaining the acidity of endosomes, lysosomes, Golgi-derived vesicles, chromaffin granules, the central vacuoles of yeast and plants, and some clathrin-coated vesicles (2). In some specific cells of the proximal tubule and collecting duct of the kidney, V-ATPases are present at high densities on the plasma membrane and have a central role in maintaining the acid-base balance of the organism (3). In osteoclasts, cells that are essential for bone remodeling, densely packed V-ATPases reside in a specialized domain of the apical plasma membrane known as the ruffled membrane, where they acidify an extracellular compartment at the site of attachment to bone (5). Osteoclast proton secretion is required both for dissolution of bone mineral and for efficient degradation of bone matrix proteins by acid cysteine proteinases (6).During the past decade, much effort has been devoted to isolating genes that encode the subunits of V-ATPases, determining how V-ATPase genes are regulated, and identifying interactions among...

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Section: Methodsmentioning

confidence: 99%

Interaction between Aldolase and Vacuolar H+-ATPase

Lu¹,

Holliday²,

Zhang³

et al. 2001

Journal of Biological Chemistry

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173

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“…Mouse Marrow Cultures-Osteoclasts were generated from primary mouse marrow cultures (12). 8 -20 g Swiss-Webster mice were killed by * This work was supported by an Arthritis Investigator Award from the Arthritis Foundation (to L. S. H.) and National Institutes of Health Grants RO1 DK52131 (to B. S. L.), RO1 DK38848 (to S. L. G.), and PO1 AR32087.…”

Section: Methodsmentioning

confidence: 99%

“…Bone Resorption Assays-Assays were performed essentially as described previously (12) with slight modifications to allow immunoprecipitations to be performed from bone resorptive cells. Mouse marrow cultures were grown to maturity in tissue culture plates, then scraped and loaded onto 8-cm 2 dentine slices in 6-well plates.…”

Section: Methodsmentioning

confidence: 99%

“…When cultured in medium containing 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ), mouse marrow cells develop into osteoclasts (11,12) that contain most of the V-ATPase in the cultures (13). Osteoclasts from 1,25-(OH) 2 D 3 -treated cultures plated on bone or dentine slices undergo a transformation to the activated phenotype, in which actin rings form, V-ATPase is polarized to the ruffled membrane, and bone is resorbed (1,2,5).…”

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Interaction between Vacuolar H+-ATPase and Microfilaments during Osteoclast Activation

Lee

Gluck

Holliday

1999

Journal of Biological Chemistry

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112

123

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Normal bone remodeling requires precise control over the rates of bone formation by osteoblasts and degradation by osteoclasts. Bone degradation entails the activation of osteoclasts to a highly polarized state, with formation of a specialized ruffled membrane at their bone attachment site that confers the ability to resorb bone. The osteoclast ruffled membrane is bounded by a ring of actin filaments and associated proteins on the cytoplasmic face of the plasma membrane, localized to the zone on the cell surface that is adherent to bone (2-4). The adherence zone forms a tightly sealed extracellular compartment that is acidified by densely packed proton-transporting V-ATPases 1 in the ruffled membrane (1, 5); acidification of this compartment promotes dissolution of bone mineral and degradation of bone matrix protein by cysteine proteinases secreted by the osteoclast (6 -8).In osteoclasts actively resorbing bone, most of the cellular V-ATPase is polarized to the ruffled membrane (1). Polarization of V-ATPases to discrete plasmalemmal domains in epithelial cells is dependent on the microtubules in the cytoskeleton (9). The involvement of actin filaments in polarization is not yet clear, although actin filament binding to V-ATPasedense vesicles has been observed in proton-transporting epithelial cells of toad urinary bladder (10).When cultured in medium containing 1,25-dihydroxyvitamin D 3 (1,25-(OH) 2 D 3 ), mouse marrow cells develop into osteoclasts (11, 12) that contain most of the V-ATPase in the cultures (13). Osteoclasts from 1,25-(OH) 2 D 3 -treated cultures plated on bone or dentine slices undergo a transformation to the activated phenotype, in which actin rings form, V-ATPase is polarized to the ruffled membrane, and bone is resorbed (1, 2, 5). In contrast, osteoclasts from identical cultures placed on glass coverslips fail to form ruffled membranes and do not have physiologically detectable plasma membrane V-ATPase (14, 15).Recent studies suggest that V-ATPase is associated with the cytoskeleton in osteoclasts cultured in vitro (16, 17). V-ATPase was found in a detergent-insoluble (cytoskeletal) fraction of osteoclast-containing bone marrow cultures from normal mice (16). In contrast, in osteoclasts from osteosclerotic (oc Ϫ /oc Ϫ ) mice, which are unable to form ruffled membranes, the amount of V-ATPase in the detergent-insoluble fraction was reduced (16), prompting speculation that V-ATPase binding to the cytoskeleton might be involved in ruffled membrane formation. In addition, genetic studies from yeast point toward an association between V-ATPase and the actin cytoskeleton (18). These authors (18) postulated that alterations in the actin cytoskeleton and cytoskeletal processes caused by mutation of V-ATPase subunits are the result of indirect effects resulting, perhaps, from changes in intracellular pH affecting cytoskeletal organization.Here, we examine the interaction between the Triton-insoluble cytoskeleton and V-ATPase in mouse marrow osteoclasts. We show that V-ATPase binds actin filaments dir...

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“…Several studies using primary cultures of osteoblast-like cells and chondrocytes, and osteoclast-containing bone marrow cultures, or cultured cell lines such as osteoblastic MC3T3-E1 cells have suggested that natriuretic peptides modulate the proliferation and differentiation of osteoblasts, chondrocytes, and osteoclasts in vitro (15)(16)(17)(18). However, whether natriuretic peptides can regulate bone formation in vivo has remained to be elucidated.…”

mentioning

confidence: 99%

Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide

Suda

Ogawa

Tanaka

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

156

101

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Longitudinal bone growth is determined by the process of endochondral ossification in the cartilaginous growth plate, which is located at both ends of vertebrae and long bones and involves many systemic hormones and local regulators. Natriuretic peptides organize a family of three structurally related peptides: atrial natriuretic peptide, brain natriuretic peptide (BNP), and C-type natriuretic peptide. Atrial natriuretic peptide and BNP are cardiac hormones that are produced predominantly by the atrium and ventricle, respectively. C-type natriuretic peptide occurs in a wide variety of tissues, where it acts as a local regulator. These peptides can inf luence body f luid homeostasis and blood pressure control through the activation of two guanylyl cyclase (GC)-coupled natriuretic peptide receptor subtypes-GC-A and GC-B. We report here marked skeletal overgrowth in transgenic mice that overexpress BNP. Transgenic mice with elevated plasma BNP concentrations exhibited deformed bony skeletons characterized by kyphosis, elongated limbs and paws, and crooked tails. Bone abnormalities resulted from a high turnover of endochondral ossification accompanied by overgrowth of the growth plate. Studies using an in vitro organ culture of embryonic mouse tibias revealed that BNP increases the height of cartilaginous primordium directly, thereby stimulating the total longitudinal bone growth. The present study demonstrates that natriuretic peptides can affect the process of endochondral ossification.

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C-type Natriuretic Peptide Increases Bone Resorption in 1,25-Dihydroxyvitamin D3-stimulated Mouse Bone Marrow Cultures

Cited by 64 publications

References 39 publications

Interaction between Aldolase and Vacuolar H+-ATPase

Interaction between Aldolase and Vacuolar H+-ATPase

Interaction between Vacuolar H+-ATPase and Microfilaments during Osteoclast Activation

Skeletal overgrowth in transgenic mice that overexpress brain natriuretic peptide

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