Transglutaminase-mediated oligomerization promotes osteoblast adhesive properties of osteopontin and bone sialoprotein

Forsprecher, Jennifer; Wang, Zhemeng; Goldberg, Harvey A.; Kaartinen, Mari T.

doi:10.4161/cam.5.1.13369

Cited by 37 publications

(30 citation statements)

References 71 publications

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“…It was confirmed that both OPN and BSP serve as substrates for TG2 and that their modification by TG2 enhanced the formation of cellular extensions in osteoblast cell cultures. Similar to Factor XIII, TG2 is found to localize to osteoid, osteoblasts, and osteocytes and it is hypothesized that these two enzymes work synergistically to oligomerize substrates [34]. …”

Section: Transglutaminasementioning

confidence: 99%

SPARC/osteonectin in mineralized tissue

2016

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Secreted protein acidic and rich in cysteine (SPARC/osteonectin/BM40) is one of the most abundant non-collagenous protein expressed in mineralized tissues. This review will focus on elucidating functional roles of SPARC in bone formation building upon results from non-mineralized cells and tissues, the phenotype of SPARC-null bones, and recent discoveries of human diseases with either dysregulated expression of SPARC or mutations in the gene encoding SPARC that give rise to bone pathologies. The capacity of SPARC to influence pathways involved in extracellular matrix assembly such as procollagen processing and collagen fibril formation as well as the capacity to influence osteoblast differentiation and osteoclast activity will be addressed. In addition, the potential for SPARC to regulate cross-linking of extracellular matrix proteins by members of the transglutaminase family of enzymes is explored. Elucidating defined biological functions of SPARC in terms of bone formation and turnover are critical. Further insight into specific cellular mechanisms involved in the formation and homeostasis of mineralized tissues will lead to a better understanding of disease progression.

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Section: Transglutaminasementioning

confidence: 99%

SPARC/osteonectin in mineralized tissue

2016

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“…Several studies have demonstrated the expression of TGM2 in bone, in areas of mineralized matrix near osteoblasts and osteocytes and in hypertrophic chondrocytes [20]. TGM2 substrates in bone include multiple collagen or non-collagenous proteins, including type I collagen, fibronectin, osteopontin, bone sialoprotein, and fetuin-A [20], with cross-linking promoting cell adhesion and migration [12,21]. TGM2 cross-linking of these proteins can stabilize the extracellular matrices rendering them resistant against proteolytic degradation [14].…”

Section: Discussionmentioning

confidence: 99%

Transglutaminase 2 Accelerates Vascular Calcification in Chronic Kidney Disease

et al. 2013

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Background: Transglutaminase 2 (TGM2) is a calcium-dependent enzyme that can cross-link nearly all extracellular matrix (ECM) proteins and can facilitate cell-ECM interaction through integrins. Given the importance of the ECM in vascular calcification we tested the hypothesis that increased TGM2 activity may accelerate vascular calcification in chronic kidney disease (CKD). Methods: We utilized thoracic aortas and vascular smooth muscle cells (VSMC) from the Cy/+ rat, a model of progressive CKD that develops arterial calcification on a normal phosphorus diet, compared to normal rats. Results: VSMC isolated from CKD rats had increased expression and activity of TGM2 compared to cells from normal rats. The increased calcification and expression of alkaline phosphatase activity observed in VSMC from CKD rats compared to normal was inhibited in a dose-dependent manner with the TGM inhibitors cystamine and Z006. Matrix vesicles (MV) from CKD rat VSMC also had increased TGM2 expression and the calcification of MV on type I collagen could be inhibited with cystamine and accelerated by exogenous cross-linking of fibronectin or type I collagen with TGM2. Finally, the calcification of aorta rings from CKD rats in ex vivo cultures was inhibited with TGM2 inhibitor. Conclusion: These data demonstrate a role of TGM2 in the pathogenesis of vascular calcification in CKD through enhancement of MV-ECM calcification.

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“…Further, the covalent isopeptide bonds often alter the monomer's conformation within the polymer and unmask cryptic binding sites for other ECM components (van den Brule et al, 1998) and cell surface receptors such as integrins (Belkin et al, 2005; Khew et al, 2008; Nishimichi et al, 2009, 2011). Thus, this type of TG2-elicited modification of matrix polymers regulates ECM structure and also promotes cell–ECM adhesion and adhesion-dependent biological responses (Belkin et al, 2005; Chau et al, 2005; Forsprecher et al, 2011; Spurlin et al, 2009). The latter phenomenon gained much attention as an underlying principle in biotechnological applications of TG2-modified matrices for cell cultures (Collighan and Griffin, 2009).…”

Section: Enzymatic and Nonenzymatic Activities Of Tg2mentioning

confidence: 99%

Cellular Functions of Tissue Transglutaminase

Nurminskaya

Belkin

2012

International Review of Cell and Molecular Biology

216

255

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Transglutaminase 2 (TG2 or tissue transglutaminase) is a highly complex multifunctional protein that acts as transglutaminase, GTPase/ATPase, protein disulfide isomerase, and protein kinase. Moreover, TG2 has many well-documented nonenzymatic functions that are based on its noncovalent interactions with multiple cellular proteins. A vast array of biochemical activities of TG2 accounts for its involvement in a variety of cellular processes, including adhesion, migration, growth, survival, apoptosis, differentiation, and extracellular matrix organization. In turn, the impact of TG2 on these processes implicates this protein in various physiological responses and pathological states, contributing to wound healing, inflammation, autoimmunity, neurodegeneration, vascular remodeling, tumor growth and metastasis, and tissue fibrosis. TG2 is ubiquitously expressed and is particularly abundant in endothelial cells, fibroblasts, osteoblasts, monocytes/macrophages, and smooth muscle cells. The protein is localized in multiple cellular compartments, including the nucleus, cytosol, mitochondria, endolysosomes, plasma membrane, and cell surface and extracellular matrix, where Ca2+, nucleotides, nitric oxide, reactive oxygen species, membrane lipids, and distinct protein–protein interactions in the local microenvironment jointly regulate its activities. In this review, we discuss the complex biochemical activities and molecular interactions of TG2 in the context of diverse subcellular compartments and evaluate its wide ranging and cell type-specific biological functions and their regulation.

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Transglutaminase-mediated oligomerization promotes osteoblast adhesive properties of osteopontin and bone sialoprotein

Cited by 37 publications

References 71 publications

SPARC/osteonectin in mineralized tissue

SPARC/osteonectin in mineralized tissue

Transglutaminase 2 Accelerates Vascular Calcification in Chronic Kidney Disease

Cellular Functions of Tissue Transglutaminase

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