Evidence for a role of proteinpolysaccharides in regulation of mineral phase separation in calcifying cartilage

Pita, Julio C.; Cuervo, L. A.; Madruga, Juan E.; Muller, Francisco J.; Howell, David S.

doi:10.1172/jci106437

Cited by 64 publications

(17 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, although hypocalcemia and hypophosphatemia easily account for the impairment in mineral deposition typical of rickets and osteomalacia (8), the disorganization of the chondrocyte columns seen in rachitic cartilage and the presence of abnormalities in the maturation of chondrocytes (8,9) are more difficult to attribute to this mechanism. Furthermore, changes in the physical properties of proteoglycan aggregates in rachitic rat bone (10) and a reduction in sulfate fixation in the matrix of growth plate cartilage in vitamin D-deficient rats have also been reported (11), findings that are consistent with the presence of abnormalities of sulfate metabolism in 1,25(OH) 2 D deficiency. Finally, the intestine and kidney, two of the principal target organs for 1,25(OH) 2 D action, are also known to represent the two most important tissues implicated in the regulation of extracellular concentrations of inorganic sulfate (12).…”

Section: Introductionmentioning

confidence: 70%

Abnormal sulfate metabolism in vitamin D-deficient rats.

Fernandes¹,

Hampson²,

Cahours³

et al. 1997

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 70%

Abnormal sulfate metabolism in vitamin D-deficient rats.

Fernandes¹,

Hampson²,

Cahours³

et al. 1997

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…Although both macromolecules undoubtedly influence the propagation of mineral from the MVs, in this study the effects of type II and X collagen on mineral formation by the synthetic complexes were studied because they are known to bind to MV (51) in an annexin-dependent manner (15) that has been shown to enhance mineral formation by the MV (52). The important inhibitory effects of cartilage proteoglycans on mineral formation (53,54) by MV and the biomimetic nucleation complex and their interactions with type II and X collagen will be explored in a future study.…”

mentioning

confidence: 99%

Mineralization of Annexin-5-containing Lipid-Calcium-Phosphate Complexes

Genge

Wuthier

2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

Matrix vesicles (MVs) in the growth plate bind to cartilage collagens and initiate mineralization of the extracellular matrix. Native MVs have been shown to contain a nucleational core responsible for mineral formation that is comprised of Mg 2؉ -containing amorphous calcium phosphate and lipid-calciumphosphate complexes (CPLXs) and the lipid-dependent Ca 2؉ -binding proteins, especially annexin-5 (Anx-5), which greatly enhances mineral formation. Incorporation of non-Ca 2؉ -binding MV lipids impedes mineral formation by phosphatidylserine (PS)-CPLX. In this study, nucleators based on amorphous calcium phosphate (with or without Anx-5) were prepared with PS alone, PS ؉ phosphatidylethanolamine (PE), or PS ؉ PE and other MV lipids. These were incubated in synthetic cartilage lymph containing no collagen or containing type II or type X collagen. Dilution of PS with PE and other MV lipids progressively retarded nucleation. Incorporation of Anx-5 restored nucleational activity to the PS:PE CPLX; thus PS and Anx-5 proved to be critical for nucleation of mineral. Without Anx-5, induction of mineral formation was slow unless high levels of Ca 2؉ were used. The presence of type II collagen in synthetic cartilage lymph improved both the rate and amount of mineral formation but did not enhance nucleation. This stimulatory effect required the presence of the nonhelical telopeptides. Although type X collagen slowed induction, it also increased the rate and amount of mineral formation. Both type II and X collagens markedly increased mineral formation by the MV-like CPLX, requiring Anx-5 to do so. Thus, Anx-5 enhances nucleation by the CPLXs and couples this to propagation of mineral formation by the cartilage collagens. Matrix vesicles (MVs),2 extracellular lipid bilayer-enclosed microstructures released by calcifying cells, initiate mineral formation in newly forming bone (1-4); there is little evidence that they play a role during the remainder of mineral deposition under the aegis of osteoblasts. However, MVs also appear to initiate ectopic calcification in calcific tendonitis, apatite-deposition osteoarthritis, cardiac valve calcification, and atherosclerotic lesions (5-8). MVs interact with both the matrix collagens (9 -11) and proteoglycans (12, 13) in the extracellular matrix. The interaction between MVs and the matrix collagens has been shown to be mediated by annexin 5 (14 -16), the major protein in MV (17-22). MV are enriched in phosphatidylserine (PS) (23, 24), a lipid that has high affinity for Ca 2ϩ (25,26) and is able to form complexes with both Ca 2ϩ and P i (27). Such complexes have the ability to nucleate hydroxyapatite formation (28 -32). PS is initially localized to the internal membrane of MV (33) where it is found in PS:Ca 2ϩ :P i complexes (CPLXs) (34). However, during programmed cell death (apoptosis) PS becomes externalized in a variety of cells (35,36); in fact externalization of PS is widely used to identify apoptotic cells (37,38). Although there are similarities between apoptotic bodies and MV, th...

show abstract

“…Various roles have also been proposed for lysozyme in cartilaginous tissues on the basis of its demonstrated in vitro interactions with connective tissue components [3,[30][31][32][33]. Lysozyme has been shown to interact with proteoglycan (PG) aggregates, the result be ing a reduction in both the size and quantity of aggregate [34]; lysozyme also complexes with hyaluronate (HA) [35,36], thus inter fering with the interaction of link protein and HA.…”

Section: Resultsmentioning

confidence: 99%

“…Since PG aggregates inhibit in vitro depo sition of calcium phosphate and PG mono mers do not [33,39], localization of lyso zyme at the cartilage-bone interface may re sult in enhanced mineral deposition. On this basis, a role for lysozyme has been proposed in endochondral ossification [30][31][32][33].…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Lysozyme, a Major Low-Molecular-Weight Cationic Protein of the Intervertebral Disc, Which Increases with Ageing and Degeneration

1989

View full text Add to dashboard Cite

Lysozyme was demonstrated to increase in content in the human intervertebral disc in a significant age-dependent manner. In young discs ( < 20 years) the levels were 440 U/g wet weight, whereas in older discs ( > 65 years) the concentration was 3,460 U/g wet weight. These findings contrasted with the hexuronate level (as a marker of proteoglycans) and neutral sugar content of the tissues which decreased with age. The level of lysozyme determined in the disc tissue also correlated with the morphological grade of disc degeneration.

show abstract

Evidence for a role of proteinpolysaccharides in regulation of mineral phase separation in calcifying cartilage

Cited by 64 publications

References 16 publications

Abnormal sulfate metabolism in vitamin D-deficient rats.

Abnormal sulfate metabolism in vitamin D-deficient rats.

Mineralization of Annexin-5-containing Lipid-Calcium-Phosphate Complexes

Lysozyme, a Major Low-Molecular-Weight Cationic Protein of the Intervertebral Disc, Which Increases with Ageing and Degeneration

Contact Info

Product

Resources

About