2016
DOI: 10.1074/mcp.m115.049718
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Osteoblast-released Matrix Vesicles, Regulation of Activity and Composition by Sulfated and Non-sulfated Glycosaminoglycans

Abstract: Our aging population has to deal with the increasing threat of age-related diseases that impair bone healing. One promising therapeutic approach involves the coating of implants with modified glycosaminoglycans (GAGs) that mimic the native bone environment and actively facilitate skeletogenesis. In previous studies, we reported that coatings containing GAGs, such as hyaluronic acid (HA) and its synthetically sulfated derivative (sHA1) as well as the naturally low-sulfated GAG chondroitin sulfate (CS1), reduce … Show more

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Cited by 49 publications
(87 citation statements)
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References 96 publications
(97 reference statements)
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“…Two studies that have characterized the proteome in mineralizing cells have shown that PLS3 is expressed in the released matrix vesicles and in the apical microvilli from which they are produced . Lipids, which are thought to be important nucleation sites for hydroxyapatite formation, are also an important component of the matrix vesicles, as well as proteins important for proteoglycan stability . Raman microspectroscopic analysis showed in our patient reduced bone matrix lipid and glycosaminoglycan contents, the latter reflecting a decreased amount of proteoglycans.…”
Section: Discussionmentioning
confidence: 50%
“…Two studies that have characterized the proteome in mineralizing cells have shown that PLS3 is expressed in the released matrix vesicles and in the apical microvilli from which they are produced . Lipids, which are thought to be important nucleation sites for hydroxyapatite formation, are also an important component of the matrix vesicles, as well as proteins important for proteoglycan stability . Raman microspectroscopic analysis showed in our patient reduced bone matrix lipid and glycosaminoglycan contents, the latter reflecting a decreased amount of proteoglycans.…”
Section: Discussionmentioning
confidence: 50%
“…MV was previously shown to play an important role in osteoblast biology. 7 We confirmed the presence of MV by using scanning electron microscopy (SEM). An SEM image of a hBMSC-derived decellularized ECM shows spherical MV embedded in fibrous collagen network structures (Figure 2A).…”
Section: Analyses Of Ecm-associated Proteins In Cells MV and Ecmmentioning
confidence: 67%
“…Another explanation for the extracellular accumulation of FN fibrils could be a reduced enzymatic FN matrix degradation by proteolytic enzymes. Previous studies showed that synthetic sHA derivatives reduced the activity of matrix metalloproteinase-2 (MMP-2), one of the FN-cleaving proteolytic enzymes1415. This MMP reduction might be triggered by the increased sHA-induced formation of MMP inhibitor TIMP-3 (tissue inhibitor of metalloproteinase-3) that could further contribute to FN accumulation via blocking MMP-related matrix degradation15.…”
Section: Discussionmentioning
confidence: 99%
“…These artificial sGAG derivatives altered several cellular processes such as various cell signalling pathways (e.g. BMP-2 (bone morphogenetic protein-2) and TGF-ÎČ1 (transforming growth factor-ÎČ1) signalling), proteins involved in endocytosis, cell-ECM-interaction, and ECM remodelling as well as matrix vesicle formation and composition131415. Sulfation of GAG was found to be the underlying factor responsible for these effects as non-sulfated HA did not alter osteogenesis in vitro .…”
mentioning
confidence: 99%