Regulatory effect of endogenous zinc and inhibitory action of toxic metal ions on calcium accumulation by matrix vesicles in vitro

Sauer, Glenn R.; Adkisson, H. Davis; Genge, Brian R.; Wuthier, Roy E.

doi:10.1016/0169-6009(89)90080-9

Cited by 50 publications

(44 citation statements)

References 23 publications

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“…Such studies should provide insight into how these aspects of MV mineralization are regulated. Kinetic studies of MV-induced mineralization typically reveal a lag period during which minimal Ca 2ϩ accumulation occurs (28,29), followed by a rapid uptake period, and finally a slower plateau phase during which apatitic crystalline mineral forms (29,30). Studies on nascent MV reveal the presence of a nucleational core that contains PS complexed with non-crystalline calcium phosphate (14).…”

Section: Discussionmentioning

confidence: 99%

Changes in Phospholipid Extractability and Composition Accompany Mineralization of Chicken Growth Plate Cartilage Matrix Vesicles

Wu¹,

Genge²,

Kang³

et al. 2002

Journal of Biological Chemistry

101

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Matrix vesicles are lipid bilayer-enclosed structures that initiate extracellular mineral formation. Little attention has been given to how newly formed mineral interacts with the lipid constituents and then emerges from the lumen. To explore whether specific lipids bind to the incipient mineral and if breakdown of the membrane is involved, we analyzed changes in lipid composition and extractability during vesicle-induced calcification. Isolated matrix vesicles were incubated in synthetic cartilage lymph to induce mineral formation. At various times, samples of the lipids were taken for analysis, extracted both before and after demineralization to remove deposited mineral. Phosphatidylserine and phosphatidylinositol both rapidly disappeared from extracts made before decalcification, indicating rapid degradation. However, extracts made after demineralization revealed that phosphatidylserine had become complexed with newly forming mineral. Concomitantly, its levels actually increased, apparently by base-exchange with phosphatidylethanolamine. Though partially complexed with the mineral, phosphatidylinositol was nevertheless rapidly broken down. Sphingomyelin and phosphatidylethanolamine also underwent rapid breakdown, but phosphatidylcholine was degraded more slowly, all accompanied by a buildup of free fatty acids. The data indicate that phosphatidylserine forms complexes that accompany mineral formation, while degradation of other membrane phospholipids apparently enables egress of crystalline mineral from the vesicle lumen. Matrix vesicles (MV)1 are extracellular microstructures released by calcifying cells that initiate mineral formation in newly forming bone (1-4). MV are enclosed by a lipid bilayer membrane that is enriched in selected phospholipids, especially phosphatidylserine (PS) (5-6), a lipid with known high affinity for Ca 2ϩ (7)(8). Initially, PS is largely confined to the inner leaflet of the MV membrane (9). Previous transmission electron microscopic (TEM) studies have shown that the first mineral formed in MV is associated with the inner aspect of the membrane (10). Later, the crystals appear to emerge through the membrane and trigger formation of radial clusters of mineral centered on the remnant of the original vesicle. How the crystals penetrate the MV membrane is currently unknown. While it is possible that simple physical force mediates this process (11), there is indirect evidence that latent lipolytic enzymes become activated during Ca 2ϩ accumulation and facilitate breakdown of the membrane. To explore this latter possibility, the composition of lipids in MV was analyzed during the course of MV-mediated mineralization in vitro.Since previous work had shown that not all lipids were readily extracted from mineralizing tissues (12-13), resident MV lipids were extracted both before and after demineralization using both neutral and acidic lipid solvents. Lipid composition was analyzed qualitatively by high performance thin layer chromatography (HPTLC) and quantitatively by high performance liq...

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Section: Discussionmentioning

confidence: 99%

Changes in Phospholipid Extractability and Composition Accompany Mineralization of Chicken Growth Plate Cartilage Matrix Vesicles

Wu¹,

Genge²,

Kang³

et al. 2002

Journal of Biological Chemistry

101

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“…Because MV are enclosed by a membrane, channel proteins are required to mediate the influx of mineral ions into these particles. Previous findings from our and other laboratories, showed that chymotrypsin treatment, which removes most of the annexins from MV, and zinc treatment, which inhibits annexin-mediated Ca 2ϩ influx into phosphatidylserine (PS)-enriched liposomes, diminished MV Ca 2ϩ uptake (12)(13)(14)(15), suggesting that annexins II, V, and VI serve as ion channels in MV, enabling Ca 2ϩ loading of the vesicles during the initial phase of mineralization.…”

mentioning

confidence: 99%

The Roles of Annexins and Types II and X Collagen in Matrix Vesicle-mediated Mineralization of Growth Plate Cartilage

Kirsch

Harrison

Golub

et al. 2000

Journal of Biological Chemistry

193

187

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Annexins II, V, and VI are major components of matrix vesicles (MV), i.e. particles that have the critical role of initiating the mineralization process in skeletal tissues. Furthermore, types II and X collagen are associated with MV, and these interactions mediated by annexin V stimulate Ca 2؉ uptake and mineralization of MV. However, the exact roles of annexin II, V, and VI and the interaction between annexin V and types II and X collagen in MV function and initiation of mineralization are not well understood. Annexins are a family of proteins that has in common the ability to bind to acidic phospholipids in the presence of Ca 2ϩ (1, 2). The family consists of at least 12 members, and three of them, annexins II, V, and VI, are highly expressed in calcifying cartilage and bone (3, 4). Annexin II and V each contain four 70 -80 amino acids repeats with an annexin consensus sequence. Annexin VI contains eight such repeats. These four or eight repeats form the conserved core region, which is responsible for the Ca 2ϩ -dependent binding of the proteins to phospholipids. In contrast, the N-terminal regions of the annexins are highly variable and may contribute to the specific functions of the various annexins (1, 2).Annexins II, V, and VI are major components of matrix vesicles (MV), 1 which are particles that, after being released from the plasma membrane of hypertrophic chondrocytes or osteoblasts, have the critical role of initiating the mineralization process in cartilage and perhaps in bone (3, 5). Three independent lines of evidence indicate that annexin II, V, and VI exhibit distinct Ca 2ϩ ion channel properties. First, when inserted into artificial phosphatidylserine bilayers they form voltage-dependent Ca 2ϩ ion channels (6 -8). Second, the crystal structures of these annexins are largely ␣-helical with parallel barrels of ␣-helical domains forming a hydrophilic, charged pore through the center of the protein (6, 8, 9). Third, annexin II, V, and VI are able to mediate Ca 2ϩ influx into artificial liposomes (10;11). It was shown that annexin-mediated Ca 2ϩ influx into liposomes is rapid during the first 20 min and then reaches a plateau after 20 min (10, 11).The initial phase of MV-mediated mineralization is characterized by the uptake of mineral ions by these particles and the formation and growth of the first mineral phase inside the vesicles (5). Because MV are enclosed by a membrane, channel proteins are required to mediate the influx of mineral ions into these particles. Previous findings from our and other laboratories, showed that chymotrypsin treatment, which removes most of the annexins from MV, and zinc treatment, which inhibits annexin-mediated Ca 2ϩ influx into phosphatidylserine (PS)-enriched liposomes, diminished MV Ca 2ϩ uptake (12-15), suggesting that annexins II, V, and VI serve as ion channels in MV, enabling Ca 2ϩ loading of the vesicles during the initial phase of mineralization.Previous studies have revealed that collagen types II and X are associated with the outer surface of MV (16). We...

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“…Although Hsu et al reported that Zn 2ϩ stimulated Ca 2ϩ uptake by rachitic rat MVs, Sauer et al provided evidence that Zn 2ϩ inhibited Ca 2ϩ influx into MVs isolated from chick hypertrophic cartilage. (16,22) Here, we provide evidence that Zn 2ϩ inhibits mineralization mediated by chick MVs by interfering with the functions of annexins II, V, and VI, and Ca 2ϩ -P i -phospholipid complexes. MVs isolated from human thyroid cartilage also contain annexins II, V, and VI and Ca 2ϩ -P i -phospholipid complexes (our unpublished observations).…”

Section: Figmentioning

confidence: 99%

“…(22) In contrast, Sauer et al demonstrated a decreased Ca 2ϩ influx into chick MVs and concluded that Zn 2ϩ might decrease initial Ca 2ϩ entry through ion channels and/or might inhibit the activity of Ca 2ϩ -P i -phospholipid complexes. (16) Thus, the exact role of Zn 2ϩ in the MVmediated mineralization process remains to be established.…”

Section: Introduction Bmentioning

confidence: 99%

“…(15)(16)(17) Experimental Zn 2ϩ deficiencies have been demonstrated to result in abnormal cartilage development, irregular and increased cartilage mineralization, and bone deformities. (18)(19)(20) On the other hand, increased levels of Zn 2ϩ are associated with decreased mineralization, which results in a disease known as osteochondrosis.…”

Section: Introduction Bmentioning

confidence: 99%

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Regulatory Roles of Zinc in Matrix Vesicle-Mediated Mineralization of Growth Plate Cartilage

Kirsch

Harrison

Worch

et al. 2000

Journal of Bone and Mineral Research

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Zinc (Zn 2؉ ) has long been known to play important roles in mineralization and ossification of skeletal tissues, but the mechanisms of Zn 2؉ action are not well understood. In this study we investigated the effects of Zn 2؉ on mineralization in a cell culture system in which terminal differentiation and mineralization of hypertrophic growth plate chondrocytes was induced by retinoic acid (RA) treatment. Addition of Zn 2؉ to RA-treated cultures decreased mineralization in a dose-dependent manner without affecting alkaline phosphatase (APase) activity. Characterization of matrix vesicles (MVs), particles that initiate the mineralization process, revealed that vesicles isolated from RA-treated and RA/Zn 2؉ -treated cultures showed similar APase activity, but vesicles from RA/Zn 2؉ -treated cultures contained significantly less Ca 2؉ and P i . MVs isolated from RA-treated cultures were able to take up Ca 2؉ and mineralize in vitro, whereas vesicles isolated from RA/Zn 2؉ -treated cultures were not able to do so. Detergent treatment, which ruptures the MV membrane and exposes preformed intravesicular Ca 2؉ -P i -phospholipid complexes, did not restore the Ca 2؉

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Regulatory effect of endogenous zinc and inhibitory action of toxic metal ions on calcium accumulation by matrix vesicles in vitro

Cited by 50 publications

References 23 publications

Changes in Phospholipid Extractability and Composition Accompany Mineralization of Chicken Growth Plate Cartilage Matrix Vesicles

Changes in Phospholipid Extractability and Composition Accompany Mineralization of Chicken Growth Plate Cartilage Matrix Vesicles

The Roles of Annexins and Types II and X Collagen in Matrix Vesicle-mediated Mineralization of Growth Plate Cartilage

Regulatory Roles of Zinc in Matrix Vesicle-Mediated Mineralization of Growth Plate Cartilage

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