Osteopontin Upregulation and Polymerization by Transglutaminase 2 in Calcified Arteries of Matrix Gla Protein-deficient Mice

Kaartinen, Mari T.; Murshed, Monzur; Karsenty, Gérard; McKee, Marc D.

doi:10.1369/jhc.6a7087.2006

Cited by 56 publications

(69 citation statements)

References 61 publications

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“…In bone, tTG2 is expressed by osteoblasts (Al-Jallad et al, 2006;Nurminskaya and Kaartinen, 2006), and its crosslinking activity plays a role in the organisation of extracellular matrix. On the contrary, a combined increased expression of tTG2 and osteopontin has been detected in calcifi ed arteries of Gla-deficient mice, a model characterised by ectopic mineral deposition: this phenomenon has been interpreted as an inducible inhibitory mechanism of calcifi cation (Kaartinen et al, 2007). In the same model, osteopontin was expressed close to macrophages, prompting the authors to suggest that osteopontin oligomers created by tTG2 may constitute a scaffold for macrophage adhesion and calcifi cation resorption (Kaartinen et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…On the contrary, a combined increased expression of tTG2 and osteopontin has been detected in calcifi ed arteries of Gla-deficient mice, a model characterised by ectopic mineral deposition: this phenomenon has been interpreted as an inducible inhibitory mechanism of calcifi cation (Kaartinen et al, 2007). In the same model, osteopontin was expressed close to macrophages, prompting the authors to suggest that osteopontin oligomers created by tTG2 may constitute a scaffold for macrophage adhesion and calcifi cation resorption (Kaartinen et al, 2007). The effect of osteopontin on resorption is further supported by the observation that, in osteopontin KO mice, administration of recombinant osteopontin induced resorption of ectopic calcifi cations (Steitz et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

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Gene expression analysis in calcific tendinopathy of the rotator cuff

Oliva

Barisani²,

Grasso³

et al. 2011

eCM

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We evaluated the expression of several genes involved in tissue remodelling and bone development in patients with calcifi c tendinopathy of the rotator cuff. Biopsies from calcifi ed and non-calcifi ed areas were obtained from 10 patients (8 women and 2 men; average age: 55 years; range: 40-68) with calcifi c tendinopathy of the rotator cuff. To evaluate the expression of selected genes, RNA extraction, cDNA synthesis and quantitative polymerase chain reaction (PCR) were performed. A signifi cantly increased expression of tissue transglutaminase (tTG)2 and its substrate, osteopontin, was detected in the calcifi c areas compared to the levels observed in the normal tissue from the same subject with calcifi c tendinopathy, whereas a modest increase was observed for catepsin K. There was also a signifi cant decrease in mRNA expression of Bone Morphogenetic Protein (BMP)4 and BMP6 in the calcifi c area. BMP-2, collagen V and vascular endothelial growth factor (VEGF) did not show signifi cant differences. Collagen X and matrix metalloproteinase (MMP)-9 were not detectable. A variation in expression of these genes could be characteristic of this form tendinopathy, since an increased level of these genes has not been detected in other forms of tendon lesions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Gene expression analysis in calcific tendinopathy of the rotator cuff

Oliva

Barisani²,

Grasso³

et al. 2011

eCM

View full text Add to dashboard Cite

show abstract

“…Kaartinen and colleagues (38) reported that MGP-deficient mice demonstrated arterial calcification, OPN upregulation, and macrophage migration and concluded that macrophages adhere to calcified elastic lamellae to promote the clearance of ectopic mineral deposits. However, there are few reports about the involvement of MGP in kidney stones.…”

Section: Discussionmentioning

confidence: 99%

Renal macrophage migration and crystal phagocytosis via inflammatory-related gene expression during kidney stone formation and elimination in mice: Detection by association analysis of stone-related gene expression and microstructural observation

Okada

Yasui

Fujii

et al. 2010

Journal of Bone and Mineral Research

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Mice have a strong ability to eliminate renal calcium oxalate crystals, and our previous examination indicated a susceptibility in which monocyte-macrophage interaction could participate in the phenomenon. To clarify the macrophage-related factors playing roles in the prevention of crystal formation in mouse kidneys, morphologic and expression studies based on microarray pathway analysis were performed. Eight-week-old male C57BL/6N mice were administered 80 mg/kg of glyoxylate by daily intraabdominal injection for 15 days, and the kidneys were extracted every 3 days for DNA microarray analysis. Based on the raw data of microarray analysis, pathway analyses of inflammatory response demonstrated macrophage activation through the increased expression of chemokine (C-X-C) ligand 1, fibronectin 1, and major histocompatability (MHC) class II. Association analysis of related gene expression values by quantitative reverse transcription polymerase chain reaction (RT-PCR) indicated the high association of chemokine (C-C) ligand 2, CD44, colony-stimulating factor 1, fibronectin 1, matrix gla protein, secreted phosphoprotein 1, and transforming growth factor b1 (TGF-b1) with the amount of both renal crystals and F4/80, a macrophage marker. Immunohistochemically, interstitial macrophages increased during the experimental course, and CD44 and MHC class II were upregulated around crystal-formation sites. Ultrastructural observation of renal macrophages by transmission electron microscopy indicated interstitial macrophage migration with the phagocytosis of crystals. In conclusion, increased expression of inflammation-related genes of renal tubular cells induced by crystal formation and deposition could induce monocyte-macrophage migration and phagocytosis via the interaction of CD44 with osteopontin and fibronectin. Such crystalremoving ability of macrophages through phagocytosis and digestion might become a new target for the prevention of stone formation. ß

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“…3 In MgpÀ/À mice, OPN initiates removal of the mineral by macrophages. 37 Of note, macrophages have also been found to be abundant near calcified areas in PXE dermis. 38 MGP has been shown to negatively regulate BMP2, a known osteoinductive protein.…”

Section: Vk-dependent Proteins In Pxe Patientsmentioning

confidence: 98%

Low serum vitamin K in PXE results in defective carboxylation of mineralization inhibitors similar to the GGCX mutations in the PXE-like syndrome

Vanakker

Martin

Schurgers

et al. 2010

Laboratory Investigation

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Soft-tissue mineralization is a tightly regulated process relying on the activity of systemic and tissue-specific inhibitors and promoters of calcium precipitation. Many of these, such as matrix gla protein (MGP) and osteocalcin (OC), need to undergo carboxylation to become active. This post-translational modification is catalyzed by the gammaglutamyl carboxylase GGCX and requires vitamin K (VK) as an essential co-factor. Recently, we described a novel phenotype characterized by aberrant mineralization of the elastic fibers resulting from mutations in GGCX. Because of the resemblance with pseudoxanthoma elasticum (PXE), a prototype disorder of elastic fiber mineralization, it was coined the PXE-like syndrome. As mutations in GGCX negatively affect protein carboxylation, it is likely that inactive inhibitors of calcification contribute to ectopic mineralization in PXE-like syndrome. Because of the remarkable similarities with PXE, we performed a comparative study of various forms of VK-dependent proteins in serum, plasma (using ELISA), and dermal tissues (using immunohistochemistry) of PXE-like and PXE patients using innovative, conformation-specific antibodies. Furthermore, we measured VK serum concentrations (using HPLC) in PXE-like and PXE samples to evaluate the VK status. In PXE-like patients, we noted an accumulation of uncarboxylated Gla proteins, MGP, and OC in plasma, serum, and in the dermis. Serum levels of VK were normal in these patients. In PXE patients, we found similar, although not identical results for the Gla proteins in the circulation and dermal tissue. However, the VK serum concentration in PXE patients was significantly decreased compared with controls. Our findings allow us to conclude that ectopic mineralization in the PXE-like syndrome and in PXE results from a deficient protein carboxylation of VK-dependent inhibitors of calcification. Although in PXE-like patients this is due to mutations in the GGCX gene, a deficiency of the carboxylation co-factor VK is at the basis of the decreased activity of calcification inhibitors in PXE.

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Osteopontin Upregulation and Polymerization by Transglutaminase 2 in Calcified Arteries of Matrix Gla Protein-deficient Mice

Cited by 56 publications

References 61 publications

Gene expression analysis in calcific tendinopathy of the rotator cuff

Gene expression analysis in calcific tendinopathy of the rotator cuff

Renal macrophage migration and crystal phagocytosis via inflammatory-related gene expression during kidney stone formation and elimination in mice: Detection by association analysis of stone-related gene expression and microstructural observation

Low serum vitamin K in PXE results in defective carboxylation of mineralization inhibitors similar to the GGCX mutations in the PXE-like syndrome

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