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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our previous studies suggested that a part of bone extracellular matrix (ECM) molecules are degraded and remodeled during embryonic bone formation. In contrast, little is known about ECM remodeling in postnatal appositional bone formation. The present study was designed to investigate expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) during experimentally initiated appositional bone formation in rats. Expressions of ECM molecules, MMPs, and TIMPs were examined using in situ hybridization. Osteoblasts and osteocytes expressed MMP2 and -8, TIMP1, -2, and -3, as well as type I collagen, osteopontin, and osteocalcin in the course of the appositional bone formation, while they showed few transcripts of MMP13. The results indicated that while osteoblasts and osteocytes in the apposed bone produce ECM molecules, they degrade ECM molecules with MMPs and regulate the degradation by inhibiting the activity of MMPs using TIMPs. Osteoblasts and osteocytes may reorganize the ECM composition to mature the bone matrix in appositional bone formation.
Anat Rec A Discov Mol Cell Evol Biol 2004 Apr
PMID:Osteoblasts and osteocytes express MMP2 and -8 and TIMP1, -2, and -3 along with extracellular matrix molecules during appositional bone formation. 1505 53

Endothelial cell survival and antiapoptotic pathways, including those stimulated by extracellular matrix, are critical regulators of vasculogenesis, angiogenesis, endothelial repair, and shear-stress-induced endothelial activation. One of these pathways is mediated by alpha(v)beta(3) integrin ligation, downstream activation of nuclear factor-kappaB, and subsequent up-regulation of osteoprotegerin (OPG). In this study, the mechanism by which OPG protects endothelial cells from death was examined. Serum-starved human microvascular endothelial cells (HMECs) plated on the alpha(v)beta(3) ligand osteopontin were protected from cell death. Immunoprecipitation experiments indicated that OPG formed a complex with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in HMECs under these conditions. Furthermore, inhibitors of TRAIL, including recombinant soluble TRAIL receptors and a neutralizing antibody against TRAIL, blocked apoptosis of serum-starved HMECs plated on the nonintegrin attachment factor poly-d-lysine. Whereas TRAIL was unable to induce apoptosis in HMECs plated on osteopontin, the addition of recombinant TRAIL did increase the percentage of apoptotic HMECs plated on poly-d-lysine. This evidence indicates that OPG blocks endothelial cell apoptosis through binding TRAIL and preventing its interaction with death-inducing TRAIL-receptors
Mol Biol Cell 2004 Jun
PMID:The role of osteoprotegerin and tumor necrosis factor-related apoptosis-inducing ligand in human microvascular endothelial cell survival. 1506 58

We have used in vitro oligodendrocyte differentiation and the in vivo remyelination model, the cuprizone model, to identify genes regulating oligodendrocyte function and remyelination. One of the genes we identified, osteopontin (opn), is a secreted glycoprotein with cytokine-like, chemotactic, and anti-apoptotic properties that contains an Arg-Gly-Asp (RGD) cell adhesion motif-mediating interactions with several integrins. Both microglia and astrocytes in demyelinating brain regions of cuprizone-fed mice expressed OPN protein. Recombinant OPN protein produced in a baculovirus expression system induced proliferation of both the rat CG-4 and the mouse Oli-neu oligodendrocyte precursor (OLP)-like cell lines in a dose-dependent manner. In addition, recombinant OPN treatment stimulated both myelin basic protein (MBP) synthesis and myelin sheath formation in mixed cortical cultures from embryonic mouse brain, an in vitro primary culture model of myelination. Interestingly, myelinating mixed cultures prepared from OPN(-/-) mice contained significantly less MBP compared to wild-type cultures after 17 days in culture. We propose that in the central nervous system, OPN may act as a novel regulator of myelination and remyelination.
Mol Cell Neurosci 2004 Apr
PMID:Osteopontin is upregulated during in vivo demyelination and remyelination and enhances myelin formation in vitro. 1508 Aug 98

Osteopontin (OPN) is a secreted glycosylated phosphoprotein that is responsive to oxidative stress and inflammation and controls cytokine production, inducible nitric oxide synthase (iNOS) expression and apoptotic cell death. In this study, we demonstrate the presence of OPN in the rat basal ganglia. Using reverse transcriptase polymerase chain reaction (RT-PCR), OPN cDNA was found in the substantia nigra, and striatum. The presence of OPN mRNA was demonstrated in the same areas of the basal ganglia, using in situ hybridisation. OPN protein was found in the SN, using Western blotting and confirmed by immunohistochemistry. The protein was localised to neurones but not to microglia or astroglia. This is the first report of the presence of OPN in the basal ganglia where it may be involved in the maintenance of neuronal viability.
Brain Res Mol Brain Res 2004 Dec 06
PMID:Osteopontin (Eta-1) is present in the rat basal ganglia. 1554 30

Osteoclast differentiation factor (ODF)/receptor activator of NF-kappaB ligand is essential for inducing the differentiation of mature osteoclasts. We find that nuclear factor Y (NF-Y) binds to the CCAAT box on the ODF promoter and regulates its basal transcriptional activity. The CCAAT box on the ODF gene is required for its transcriptional induction by vitamin D3, suggesting that NF-Y coregulates this promoter along with VDR. Chromatin immunoprecipitation analysis reveals that NF-Y is required for the recruitment of RNA polymerase II (RNAPII) and TATA box binding protein on the ODF promoter. Stimulation with vitamin D3 facilitates the recruitment of VDR and p300 onto the ODF promoter, resulting in acetylation of histone H4 in an NF-Y-independent manner. ODF gene induction by parathyroid hormone or prostaglandin E is also dependent on NF-Y. Furthermore, NF-Y is essential for the recruitment of RNAPII onto other CCAAT box-containing promoters, such as those of osteopontin, CYP24, and E2F1. These results suggest that NF-Y recruits RNAPII and general transcription factors onto various CCAAT box-containing promoters in response to various inductions to permit strong transcriptional activation independently of histone modifications.
Mol Cell Biol 2005 Jan
PMID:NF-Y is essential for the recruitment of RNA polymerase II and inducible transcription of several CCAAT box-containing genes. 1560 70

Northern blotting, RT-PCR, and Western blotting techniques were used to characterize the matrix constituents of avian cortical and medullary bone. Extracts of bone tissue were found to contain multiple isoforms of bone sialoprotein (BSP), osteopontin (OPN), osteonectin (ON), osteocalcin (OC), and dentin matrix protein-1 (DMP-1). Only single transcripts were observed with Northern blotting; therefore it was concluded that the isoforms were due to differences in post-translational modifications. Since medullary bone is rich in keratan sulfate (KS), RT-PCR was used to investigate the expression of known keratan sulfate-containing proteoglycans (KSPGs). Although this tissue was found to express lumican and osteoglycin/mimecan, there was little evidence to suggest that these proteoglycans were a major source of the keratan sulfate glycosaminoglycans. Treatment of medullary bone extracts with keratanase resulted in the appearance of a BSP immunoactive band of approximately 59 kDa. However, it was not possible to isolate and identify the intact keratan sulfate proteoglycan.
Comp Biochem Physiol B Biochem Mol Biol 2005 Apr
PMID:Characterization of the non-collagenous proteins in avian cortical and medullary bone. 1576 22

Following a severe ischemic injury or myocardial infarction, the extracellular matrix (ECM) of the heart is involved in pathophysiological conditions such as dilatation and cardiac dysfunction. Osteopontin (OPN) has been shown to interact with fibronectin suggesting its possible role in matrix organization, stability and wound healing. There is increased expression of OPN in several tissues in response to injury. Therefore, we tested the hypothesis that acute ischemia (2 h), followed by reperfusion (4 h) may induce early OPN and fibronectin in an isolated hemoperfused working porcine heart model. Twenty hearts were prepared and connected to a perfusion system. After 1 h of perfusion, these hearts were randomized to two groups: ten infarcted (MI, ramus circumflexus) and ten non-infarcted hearts (C). In addition, cardiac fibroblasts derived from infarcted, remote and control myocardium were investigated. In both groups, the heart rate, electrolytes, pH, blood gases, and lactate remained similar. The LVEDP and perfusion pressure of MI hearts increased significantly (P<0.05). The total fibronectin and OPN volume contents were clearly elevated in the infarct area. The matrix metalloproteinases (MMP-1 and MMP-8), fibronectin, OPN, TGF-beta1 proteins and the mRNAs for fibronectin, TGF-beta1, and OPN were significantly elevated in the infarct area as compared to the remote area and the non-infarcted hearts. Simultaneously, circulating carboxyterminal propeptide of type I procollagen (PICP) was released in the perfusion medium (threefold versus C). Fibroblast-like cells originating from the infarct area exhibited an enhanced OPN and fibronectin gene and protein expression compared to fibroblasts derived from control myocardium. Our data demonstrate the early appearance of the MMPs (increased collagen degrading enzymes) and PICP (a collagen synthesis marker) following ischemia and reperfusion. Moreover, OPN, fibronectin and TGF-beta1 protein and gene expression are elevated after ischemia and reperfusion in the ex vivo working hemoperfused porcine heart model.
J Mol Med (Berl) 2005 Aug
PMID:Increase of fibronectin and osteopontin in porcine hearts following ischemia and reperfusion. 1577 Apr 97

Tumor progression is a multistep process, which enables cells to evolve from benign to malignant tumors. This progression has been suggested to depend on six essential characteristics identified as the "hallmarks of cancer," which include: self-sufficiency in growth signals, insensitivity to growth-inhibitory signals, evasion of apoptosis, limitless replicative potential, sustained angiogenesis, and tissue invasion and metastasis. Osteopontin (OPN) is an integrin-binding protein that has been shown to be associated with the progression of several cancer types, and to play an important functional role in various aspects of malignancy, particularly tissue invasion and metastasis. Here we studied genes regulated by OPN in a model of human breast cancer using oligonucleotide microarray technology by comparing the gene-expression profiles of 21NT mammary carcinoma cells transfected to overexpress OPN versus mock-transfected control cells. From over 12,000 human genes, we identified 99 known human genes differentially regulated by OPN whose expression changed by at least 1.5-fold and showed statistically significant differences in mean expression levels between groups. Functional classification of these genes into the hallmarks of cancer categories showed that OPN can affect the expression of genes involved in all six categories in this model. Furthermore, we were able to validate the expression of 18/19 selected candidate genes by quantitative real-time PCR, further supporting our microarray findings. This study provides the first evidence that OPN can lead to numerous gene expression changes that influence multiple aspects of tumor progression and malignant growth.
Mol Carcinog 2005 Aug
PMID:Osteopontin induces multiple changes in gene expression that reflect the six "hallmarks of cancer" in a model of breast cancer progression. 1586

Vascular calcification is a regulated process of biomineralization resembling osteogenesis. Many bone-related factors, including resorptive osteoclast-like cells, although in low abundance, have been found in calcified atherosclerotic lesions. The regulatory mechanisms governing them in the vasculature, however, are not clear. Previously, we found that calcifying vascular cells (CVC), a subpopulation of bovine aortic smooth muscle cells (BASMC), undergo osteoblastic differentiation and form mineralized nodules. Since osteoblasts and marrow stromal preosteoblasts regulate osteoclastic differentiation in bone, we hypothesized that vascular cells also regulate differentiation of osteoclastic precursors in the artery wall. Peripheral blood monocytes, which are osteoclast precursors, were co-cultured with CVC or BASMC. Results showed that monocytes co-cultured with both of the vascular cells yielded fewer resorption pits than monocytes cultured alone. Furthermore, monocytes co-cultured with CVC had fewer resorption pits than those co-cultured with BASMC. Conditioned media from the vascular cells also inhibited resorptive activity of monocytes suggesting that the inhibitory effect was mediated in part by soluble factors. Compared with BASMC, CVC had lower mRNA expression for osteopontin, which promotes osteoclast attachment, but greater mRNA expression for the soluble inhibitory cytokine, IL-18. Increased osteoclastic differentiation was observed when neutralizing antibody to IL-18 receptor was added to the cultures of preosteoclasts with CVC conditioned media. Osteoprotegerin, another osteoclast inhibitory cytokine, was expressed at similar levels in both cultures. These results suggest that vascular cells inhibit osteoclastic differentiation, and that CVC have greater inhibitory effects than BASMC.
J Mol Cell Cardiol 2005 Aug
PMID:Regulation of RANKL-induced osteoclastic differentiation by vascular cells. 1589 66

To study the complex interaction between oxidative injury and the pathogenesis of vascular disease, vascular gene expression was examined in male Sprague-Dawley rats given 35 or 70 mg/kg allylamine, a synthetic amine converted to acrolein and hydrogen peroxide within the vascular wall. Vascular lesions and extensive vascular remodeling, coupled to increased production of 8-epi-PGF2alpha, nuclear localization of NFkappaB, and alterations in glutathione homeostasis, were observed in animals treated with allylamine for up to 20 days. Transcriptional profiling, immunohistochemistry, and in situ hybridization showed that genes involved in adhesion and extracellular matrix (ECM) (alpha(1) integrin, collagen), cytoskeletal rearrangements (alpha-smooth muscle actin, alpha-tropomyosin), and signal transduction (NFkappaB, osteopontin, and LINE) were altered by oxidant treatment. To evaluate mechanisms of gene dysregulation, cultured aortic smooth muscle cells were challenged with allylamine or its metabolites and processed for molecular analysis. These agents increased formation of reactive oxygen species and elicited changes in gene expression similar to those observed in vivo. Oxidative stress and changes in gene expression were inhibited by N-acetyl cysteine, a precursor of glutathione. These results indicate that genes along the ECM-integrin-cytoskeletal axis, in addition to LINE, are molecular targets in oxidant-induced vascular injury.
J Mol Cell Cardiol 2005 Jun
PMID:Novel genomic targets in oxidant-induced vascular injury. 1591 Aug 82


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