The role of matrix vesicles in growth plate development and biomineralization

Anderson, H. Clarke; Garimella, Rama Murthy; Se, Tague

doi:10.2741/1576

Cited by 276 publications

(245 citation statements)

References 132 publications

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“…1 G and H), suggesting that HAP spherule formation may precede protein build-up and the consequent formation of this component of sub-RPE deposits. Moreover, the spherules described here differ overtly from the 100-nm matrix vesicles implicated in bone formation, which have distinct crystals of HAP enclosed within a lipid shell (34). It is also important to note that immunostaining for several sub-RPE deposit-associated proteins did not show a spherular staining pattern (35); therefore, it appears that there is a selectivity of protein binding to HAP.…”

Section: Significancementioning

confidence: 86%

Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye

Thompson

Reffatto

Bundy³

et al. 2015

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

101

113

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Accumulation of protein- and lipid-containing deposits external to the retinal pigment epithelium (RPE) is common in the aging eye, and has long been viewed as the hallmark of age-related macular degeneration (AMD). The cause for the accumulation and retention of molecules in the sub-RPE space, however, remains an enigma. Here, we present fluorescence microscopy and X-ray diffraction evidence for the formation of small (0.5–20 μm in diameter), hollow, hydroxyapatite (HAP) spherules in Bruch’s membrane in human eyes. These spherules are distinct in form, placement, and staining from the well-known calcification of the elastin layer of the aging Bruch’s membrane. Secondary ion mass spectrometry (SIMS) imaging confirmed the presence of calcium phosphate in the spherules and identified cholesterol enrichment in their core. Using HAP-selective fluorescent dyes, we show that all types of sub-RPE deposits in the macula, as well as in the periphery, contain numerous HAP spherules. Immunohistochemical labeling for proteins characteristic of sub-RPE deposits, such as complement factor H, vitronectin, and amyloid beta, revealed that HAP spherules were coated with these proteins. HAP spherules were also found outside the sub-RPE deposits, ready to bind proteins at the RPE/choroid interface. Based on these results, we propose a novel mechanism for the growth, and possibly even the formation, of sub-RPE deposits, namely, that the deposit growth and formation begin with the deposition of insoluble HAP shells around naturally occurring, cholesterol-containing extracellular lipid droplets at the RPE/choroid interface; proteins and lipids then attach to these shells, initiating or supporting the growth of sub-RPE deposits.

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Section: Significancementioning

confidence: 86%

Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye

Thompson

Reffatto

Bundy³

et al. 2015

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

101

113

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“…They were initially characterized in reference to their role in pathologic mineralization in cartilage in studies 15 which mirrored those of matrix vesicles derived from growth plate cartilage and other normally mineralizing tissues. ACVs contain enzymes, ions and substrates necessary for mineral formation [74]. The presence of these ACVs explain why cytoplasmic/membrane proteins, such as annexins, have been identified in the secretome of the chondrocytes.…”

Section: Discussionmentioning

confidence: 99%

Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis

Sanchez

Bay‐Jensen

Pap

et al. 2017

Osteoarthritis and Cartilage

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The extracellular matrix (ECM) of articular cartilage is comprised of complex networks of proteins and glycoproteins, all of which are expressed by its resident cell, the chondrocyte. Cartilage is a unique tissue given its complexity and ability to resist repeated load and deformation. The mechanisms by which articular cartilage maintains its integrity throughout our lifetime is not fully understood, however there are numerous regulatory pathways known to govern ECM turnover in response to mechanical stimuli. To further our understanding of this field, we envision that proteomic analysis of the secretome will provide information on how the chondrocyte remodels the surrounding ECM in response to load, in addition to providing information on the metabolic state of the cell. In this review, we attempt to summarize the recent mass spectrometry-based proteomic discoveries in healthy and diseased cartilage and chondrocytes, to facilitate the discovery of novel biomarkers linked to degenerative pathologies, such as osteoarthritis (OA).

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“…40 Interestingly, these proteins are recurrently identified in matrix vesicles (MV), 14,41 the organelles implicated in initiation of mineralization. 41,43 Start of mineral deposition occurs by accommodating the proper environment for crystal growth in the MV. This implicates mobilization of calcium and phosphate to form hydroxyapatite.…”

Section: Discussionmentioning

confidence: 99%

“…Other studies showed that osteoblasts overexpressing ANXA2 show enhanced mineralization. 46 ANXA2 is a calcium-dependent phospholipid binding protein located in the ECM and in MV 14,43 where they are thought to be important for Ca 2+ uptake. 47 The fact that we observed the highest expression of ANXA2 in the premineralization phase might be associated with increasing ALP activity verified at this stage and the start of Ca 2+ uptake into the MV.…”

Section: Research Articlesmentioning

confidence: 99%

Proteomic Analysis of Human Osteoblastic Cells: Relevant Proteins and Functional Categories for Differentiation

et al. 2010

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Osteoblasts are the bone forming cells, capable of secreting an extracellular matrix with mineralization potential. The exact mechanism by which osteoblasts differentiate and form a mineralized extracellular matrix is presently not fully understood. To increase our knowledge about this process, we conducted proteomics analysis in human immortalized preosteoblasts (SV-HFO) able to differentiate and mineralize. We identified 381 proteins expressed during the time course of osteoblast differentiation. Gene ontology analysis revealed an overrepresentation of protein categories established as important players for osteoblast differentiation, bone formation, and mineralization such as pyrophosphatases. Proteins involved in antigen presentation, energy metabolism and cytoskeleton rearrangement constitute other overrepresented processes, whose function, albeit interesting, is not fully understood in the context of osteoblast differentiation and bone formation. Correlation analysis, based on quantitative data, revealed a biphasic osteoblast differentiation, encompassing a premineralization and a mineralization period. Identified differentially expressed proteins between mineralized and nonmineralized cells include cytoskeleton (e.g., CCT2, PLEC1, and FLNA) and extracellular matrix constituents (FN1, ANXA2, and LGALS1) among others. FT-ICR-MS data obtained for FN1, ANXA2, and LMNA shows a specific regulation of these proteins during the different phases of osteoblast differentiation. Taken together, this study increases our understanding of the proteomics changes that accompany osteoblast differentiation and may permit the discovery of novel modulators of bone formation.

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The role of matrix vesicles in growth plate development and biomineralization

Cited by 276 publications

References 132 publications

Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye

Identification of hydroxyapatite spherules provides new insight into subretinal pigment epithelial deposit formation in the aging eye

Chondrocyte secretome: a source of novel insights and exploratory biomarkers of osteoarthritis

Proteomic Analysis of Human Osteoblastic Cells: Relevant Proteins and Functional Categories for Differentiation

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