Mechanisms of calcium disposal from osteoclastic resorption hemivacuole

One of the most remarkable but neglected aspects of osteoclast function is its unique adaptation that allows the cell to function despite its resorbing surface being exposed to extremely high levels of ambient Ca2+. Recently our studies have provided evidence of continuous transcellular Ca2+ disposal, suggesting that osteoclasts are able to prevent Ca2+ accumulation within the resorptive hemivacuole. It has also been shown that matrix protein degradation products that accumulate within the osteoclast resorptive vacuole are also undergoing transcellular transport by transcytosis. However, both experimental evidence and theoretical considerations suggest that transcellular transport of Ca2+ and matrix protein is likely to occur via distinct routes. In light of these considerations, we are able to provide convincing explanations for the apparent anomalies of osteoclast intracellular [Ca2+] responses to a variety of endocrine stimuli. The understanding of the mechanisms involved in Ca2+ handling by osteoclasts indicates the lack of a simple link between osteoclast function and changes in overall cytosolic [Ca2+].

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Regiospecificty in the heterocyclization of β-oxonitriles to 5-substituted 4-oxothiazolidine derivatives

Journal of the Serbian Chemical Society ◽

10.2298/jsc0305383m ◽

2003 ◽

Vol 68 (4-5) ◽

pp. 383-390 ◽

Cited By ~ 1

Author(s):

Rade Markovic ◽

Zdravko Dzambaski ◽

Milovan Stojanovic ◽

Peter Steel ◽

Marija Baranac

Keyword(s):

Experimental Evidence ◽

Reasonable Explanation ◽

Theoretical Considerations ◽

Derivatives Of

Astudy on the regiospecificity of the base-catalyzed reaction of activated ?-oxonitriles 1 with diethyl mercaptosuccinate affording the title compounds 3 is reported. Other competitive heterocyclic products, that is 4-oxo-1,3-thiazinanes 4, derivatives of tetrahydrothiophene 5 and/or thiacyclohexane 6 which on the grounds of mechanistic considerations could be formed, were not observed. Spectroscopic and experimental evidence together with theoretical considerations, provides a reasonable explanation for the observed regiospecificity.

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The cell biology of osteoclast function

Journal of Cell Science ◽

10.1242/jcs.113.3.377 ◽

2000 ◽

Vol 113 (3) ◽

pp. 377-381 ◽

Cited By ~ 24

Author(s):

H.K. Vaananen ◽

H. Zhao ◽

M. Mulari ◽

J.M. Halleen

Keyword(s):

Bone Resorption ◽

Cell Biology ◽

Degradation Products ◽

Bone Matrix ◽

Organic Matrix ◽

Endosomal Membrane ◽

Multinucleated Cells ◽

Sealing Zone ◽

Ruffled Border ◽

Osteoclast Function

Osteoclasts are multinucleated cells responsible for bone resorption. They have developed an efficient machinery for dissolving crystalline hydroxyapatite and degrading organic bone matrix rich in collagen fibers. When initiating bone resorption, osteoclasts become polarized, and three distinct membrane domains appear: a ruffled border, a sealing zone and a functional secretory domain. Simultaneously, the cytoskeleton undergoes extensive re-organisation. During this process, the actin cytoskeleton forms an attachment ring at the sealing zone, the membrane domain that anchors the resorbing cell to bone matrix. The ruffled border appears inside the sealing zone, and has several characteristics of late endosomal membrane. Extensive vesicle transport to the ruffled border delivers hydrochloric acid and proteases to an area between the ruffled border and the bone surface called the resorption lacuna. In this extracellular compartment, crystalline hydroxyapatite is dissolved by acid, and a mixture of proteases degrades the organic matrix. The degradation products of collagen and other matrix components are endocytosed, transported through the cell and exocytosed through a functional secretory domain. This transcytotic route allows osteoclasts to remove large amounts of matrix-degradation products without losing their tight attachment to underlying bone. It also facilitates further processing of the degradation products intracellularly during the passage through the cell.

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THE DETERMINATION OF TERMINAL PROTEIN-BOUND FUCOSE

Canadian Journal of Biochemistry ◽

10.1139/o65-201 ◽

1965 ◽

Vol 43 (11) ◽

pp. 1807-1811 ◽

Cited By ~ 10

Author(s):

G. Gyorky ◽

J. C. Houck

Keyword(s):

Protein Degradation ◽

Spectrophotometric Determination ◽

Trichloroacetic Acid ◽

Degradation Products ◽

Dilute Acid ◽

Terminal Protein ◽

Residual Protein ◽

Color Yield ◽

Fucose Content

The spectrophotometric determination of protein-bound fucose is badly compromised by spurious chromagens developed from protein degradation products. To minimize the contribution of these spurious products to the color yield of fucose, the glycoprotein was partially hydrolyzed in dilute acid, thus releasing the terminal carbohydrate from the protein moieties, and the residual protein was removed with trichloroacetic acid. That the fucose content of this supernatant was real was confirmed by paper chromatography and spectral studies.The spurious chromagens were shown to result from the interaction of protein degradation products and galactose.

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Peroxisome-associated matrix protein degradation in Arabidopsis

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0811329106 ◽

2009 ◽

Vol 106 (11) ◽

pp. 4561-4566 ◽

Cited By ~ 62

Author(s):

M. J. Lingard ◽

M. Monroe-Augustus ◽

B. Bartel

Keyword(s):

Protein Degradation ◽

Matrix Protein ◽

Associated Matrix

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Influence of NH4CI on Polarized Release of Endogenous Protein Degradation Products and on Morphology in LLC-PK1 Cells

American Journal of Nephrology ◽

10.1159/000013561 ◽

2000 ◽

Vol 20 (1) ◽

pp. 74-81 ◽

Cited By ~ 4

Author(s):

Eva Wardelmann ◽

Hong Ling ◽

Inge Heim ◽

Harald Schlebusch ◽

August Heidland ◽

...

Keyword(s):

Protein Degradation ◽

Degradation Products ◽

Endogenous Protein

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Commonalities and Differences in the Interpretation of Predicates of Personal Taste vs. Relational Locative Expressions: Some Theoretical Considerations and Experimental Evidence

Open Library of Humanities ◽

10.16995/olh.513 ◽

2020 ◽

Vol 6 (2) ◽

Author(s):

Johanna Klages ◽

Anke Holler ◽

Elsi Kaiser ◽

Thomas Weskott

Keyword(s):

Experimental Evidence ◽

Personal Taste ◽

Predicates Of Personal Taste ◽

Locative Expressions ◽

Theoretical Considerations

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CHARACTERISTICS OF CYTOKINE REGULATION AND CARTILAGINOUS TISSUE METABOLISM AT PRIMARY AND POST-TRAUMATIC OSTEOARTHRITIS

Medical academic journal ◽

10.17816/maj191s119-21 ◽

2019 ◽

Vol 19 (1S) ◽

pp. 19-21

Author(s):

E V Gladkova ◽

A N Ivanov

Keyword(s):

Matrix Protein ◽

Degradation Products ◽

Type Ii Collagen ◽

System Level ◽

Control Group ◽

Cartilaginous Tissue ◽

Correlation Relationship ◽

Tissue Metabolism ◽

Regulatory Influence ◽

Post Traumatic

Cytokine system and cartilaginous tissue metabolism of 27 women affected by 0-1 stage of primary and 19 women affected by 0-1 stage of post-traumatic osteoarthritis (OA) have been studied as well as of 10 healthy persons of the control group. The enzyme-linked immunoassay method was used to determine the content of cartilage oligometric matrix protein (СOMP), cartilage glucoprotein (YKL-40), interleukins (ILs) 4 and 1β in blood serum, collagen fragments (CTX II) in urine. It was found that СOMP, CTX II, YKL-40 and IL-1β concentrations grew at more intensive rate in case of primary OA compared to post-traumatic OA. The diminution of correlation relationship strength in IL-1β serum concentrations is noted with the system level of cartilaginous tissue degradation products on the background of YKL-40 regulatory influence buildup which is more prominent with primary OA than it is with the post-traumatic one. Conclusions: early stages of primary OA are characterized by more prominent degenerative changes in the joint hyaline cartilage due to losses of type II collagen and hyperproduction of proinflammatory link cytokines with the background of YKL-40 regulatory influence buildup and reduction of the IL-1β influence. The changes of cartilaginous tissue metabolism with post-traumatic OA were characterized by preservation of dependence on IL-1β serum concentration with the background of reduction of YKL-40 influence.

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The quantitative determination of glycosaminoglycans in urine with Alcian Blue 8GX

Biochemical Journal ◽

10.1042/bj1310351 ◽

1973 ◽

Vol 131 (2) ◽

pp. 351-357 ◽

Cited By ~ 119

Author(s):

P. Whiteman

Keyword(s):

Quantitative Determination ◽

Experimental Evidence ◽

Alcian Blue ◽

Preceding Paper ◽

Mgcl2 Concentration ◽

Theoretical Considerations ◽

Urinary Glycosaminoglycans

1. The effect of MgCl2 concentration on the interaction of Alcian Blue 8GX and glycosaminoglycans in the urine of patients with mucopolysaccharidosis was studied by using a new quantitative micro method for the measurement of Alcian Blue–glycosaminoglycan complexes. This provided a means of measuring the critical electrolyte concentrations of urinary glycosaminoglycans. 2. Theoretical considerations based on the preceding paper (Whiteman, 1973) and experimental evidence provided here show that Alcian Blue 8GX may be used for the direct quantitative determination of total urinary glycosaminoglycans. The method is simple, requires sample volumes of 50μl or less, and gives results comparable with those obtained by other more complicated methods.

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pH dependence of bone resorption: mouse calvarial osteoclasts are activated by acidosis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2001.280.1.e112 ◽

2001 ◽

Vol 280 (1) ◽

pp. E112-E119 ◽

Cited By ~ 68

Author(s):

Sajeda Meghji ◽

Matthew S. Morrison ◽

Brian Henderson ◽

Timothy R. Arnett

Keyword(s):

Ph Dependence ◽

Critical Role ◽

Prostaglandin E ◽

Acid Base Balance ◽

Dihydroxyvitamin D ◽

Osteoclastic Resorption ◽

Base Balance ◽

Neonatal Mouse Calvaria ◽

Osteoclast Function ◽

Ph Range

We examined the effects of HCO3 − and CO2 acidosis on osteoclast-mediated Ca2+ release from 3-day cultures of neonatal mouse calvaria. Ca2+ release was minimal above pH 7.2 in control cultures but was stimulated strongly by the addition of small amounts of H+ to culture medium (HCO3 − acidosis). For example, addition of 4 meq/l H+ reduced pH from 7.12 to 7.03 and increased Ca2+ release 3.8-fold. The largest stimulatory effects (8- to 11-fold), observed with 15–16 meq/l added H+, were comparable to the maximal Ca2+ release elicited by 1,25-dihydroxyvitamin D3[1,25(OH)2D3; 10 nM], parathyroid hormone (10 nM), or prostaglandin E2 (1 μM); the action of these osteolytic agents was attenuated strongly when ambient pH was increased from ∼7.1 to ∼7.3. CO2 acidosis was a less effective stimulator of Ca2+ release than HCO3 −acidosis over a similar pH range. Ca2+ release stimulated by HCO3 − acidosis was almost completely blocked by salmon calcitonin (20 ng/ml), implying osteoclast involvement. In whole mount preparations of control half-calvaria, ∼400 inactive osteoclast-like multinucleate cells were present; in calvaria exposed to HCO3 − acidosis and to the other osteolytic agents studied, extensive osteoclastic resorption, with perforation of bones, was visible. HCO3 − acidosis, however, reduced numbers of osteoclast-like cells by ∼50%, whereas 1,25(OH)2D3 treatment caused increases of ∼75%. The results suggest that HCO3 − acidosis stimulates resorption by activating mature osteoclasts already present in calvarial bones, rather than by inducing formation of new osteoclasts, and provide further support for the critical role of acid-base balance in controlling osteoclast function.

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