JDR JDR Most Cited Articles
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kaartinen, M.T.
Right arrow Articles by McKee, M.D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kaartinen, M.T.
Right arrow Articles by McKee, M.D.
J Dent Res 84(7):607-612, 2005
© 2005 International and American Associations for Dental Research

RESEARCH REPORT
Biological

Transglutaminase Crosslinking of SIBLING Proteins in Teeth

M.T. Kaartinen1,*,2, W. Sun1, N. Kaipatur1, and M.D. McKee1,3

1 Division of Oral Biology, Faculty of Dentistry, McGill University, Strathcona Bldg.-Room M34, 3640 University Street, Montreal, QC, Canada H3A 2B2;
2 Division of Experimental Medicine, Department of Medicine, Faculty of Medicine, McGill University, QC, Canada; and
3 Department of Anatomy and Cell Biology, Faculty of Medicine, McGill University, Montreal, QC, Canada;

* corresponding author, mari.kaartinen{at}mcgill.ca


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 MATERIALS & METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Transglutaminase 2 (TG2), a protein-crosslinking enzyme, participates in extracellular matrix maturation and cell adhesion in cartilage and bone. We hypothesized that TG2 has similar roles in teeth. A TG activity assay and immunoblotting of rat tooth extracts showed TG activity and the presence of high-molecular-weight forms of the SIBLING (Small Integrin-Binding LIgand N-linked Glycoprotein) proteins: dentin matrix protein 1 (DMP1), dentin phosphoprotein (DPP), and bone sialoprotein (BSP). DMP1 and BSP, each containing both glutamine and lysine residues critical for crosslink formation, readily formed polymers in vitro when incubated with TG2. The ability of glutamine-lacking DPP to form polymers in vitro and in vivo demonstrates that it could act as a lysine donor for crosslinking, potentially having protein crosslinking partner(s) in teeth. Consistent with a role in cell adhesion, the TG2 isoform was co-localized by immunohistochemistry with its substrates at cell-matrix adhesion sites, including along odontoblast tubules (DMP1 and DPP), in the pericellular matrix of cementocytes (DMP1), and in predentin (BSP).

KEY WORDS: transglutaminase • crosslinking • SIBLING proteins • teeth • extracellular matrix


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
MATERIALS & METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
During the formation and maturation of extracellular matrices that mineralize, extracellular matrix (ECM) proteins are post-translationally modified and assembled into macromolecular structures that function in cell adhesion, cell differentiation, and biomineralization. In most mineralized tissues (excluding enamel), ECM maturation typically involves assembly, crosslinking, and organization of collagen fibrils into a supramolecular network, within which reside many non-collagenous proteins. Recent reports indicate that, like polymerized collagen, certain of these non-collagenous proteins, many of which belong to the SIBLING (Small Integrin-Binding LIgand N-linked Glycoprotein) protein family (Fisher and Fedarko, 2003), are also structured at the macromolecular scale. The SIBLING protein family includes dentin sialophosphoprotein (DSPP) [which is post-translationally cleaved into dentin phosphoprotein (DPP) and dentin sialoprotein (DSP)], osteopontin (OPN), bone sialoprotein (BSP), dentin matrix protein 1 (DMP1), and matrix extracellular glycoprotein (MEPE). Dentin phosphoprotein (also known as phosphophoryn and dentin matrix protein 2) can undergo calcium- and magnesium-ion-dependent ionic self-association to form large, 25-nm complexes in vitro (Stetler-Stevenson and Veis, 1983, 1987; Marsh, 1989). DMP1 has recently been reported to self-assemble and to facilitate mineral nucleation (He et al., 2003). Bone acidic glycoprotein-75 (BAG-75), which is closely related to the SIBLING proteins, has been shown to self-associate into large aggregates in the ECM that potentially sequester phosphate ions to facilitate mineral deposition (Gorski et al., 1997). Likewise, osteopontin (OPN) is known to dimerize in solution (Goldsmith et al., 2002) and to assemble, in an enzymatic process, into large polymers which undergo a conformational change that alters the binding of OPN to collagen (Kaartinen et al., 1999).

Although the mechanisms by which non-collagenous proteins arrange into high-molecular-weight assemblies are not fully known, analysis of accumulating data indicates that transglutaminase (TG) enzymes, particularly the TG2 isoform, have an important role in these processes. TG2 (also known as tissue transglutaminase) belongs to a family of Ca2+ ion-dependent enzymes that catalyze the formation of inter- and intramolecular covalent crosslinks between specific glutamine and lysine residues or primary amines (Lorand and Graham, 2003). These isopeptide bonds are resistant to normal proteolysis, and therefore their presence can increase the stability of protein complexes in a manner similar to that known for collagen and elastic fibers. TG2 has a key role in cell adhesion as a ß1 and ß3 integrin-binding co-receptor for fibronectin (Akimov et al., 2000). Moreover, many other Arg-Gly-Asp (RGD)-containing, integrin-binding cell adhesion proteins—such as vitronectin, OPN, and BSP—are substrates for TG2 (Esposito and Caputo, 2005).

There are several reports on TG2 expression and localization in the cells and extracellular matrices of cartilage and bone (Aeschlimann et al., 1996; Heath et al., 2001; Johnson et al., 2001; Kaartinen et al., 2002; Nurminskaya et al., 2003). Among these is our recent report describing TG activity in intramembranous rat bone extracts, and immunolocalization of TG2 and isopeptide bonds in osteoblasts, osteoid, and the pericellular matrix of osteocytes—observations consistent with the participation of TG2 in osteoblast and osteocyte adhesion and in the maturational events preceding mineralization (Kaartinen et al., 2002). In the same report, we also identified major non-collagenous protein substrates of TG2 in bone—namely, osteopontin (OPN), bone sialoprotein (BSP), and {alpha}2HS-glycoprotein (Kaartinen et al., 2002). In the present study, we have used similar approaches to investigate TG activity and localization in rat teeth, and report the finding of 2 novel TG substrates in vivo, DMP1 and DPP.


   MATERIALS & METHODS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS & METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Protein Extraction from Teeth
Rat teeth (whole incisors from three-month-old male CD rats; Charles River Laboratories, St. Constant, QC, Canada) were ground under liquid nitrogen, followed by sequential extraction with 4 mol/L guanidium-HCl (G1-extract), 0.5 mol/L EDTA (E-extract), and 4 mol/L guanidium-HCl (G2-extract) as described previously (Goldberg et al., 1988; Kaartinen et al., 2002). This study followed procedures approved by the Animal Care Committee of McGill University.

Transglutaminase Activity and Substrate Identification
TG activity and substrate identification were determined in vivo from tooth extracts by a combination of Western blotting, biotin-avidin-affinity chromatography, and detection of primary amine incorporation, as we described previously for E-extracts from bone (Kaartinen et al., 2002). SIBLING protein polymerization and primary amine incorporation into TG-reactive glutamines of DMP1 and DSP were performed in vitro with 2 µg of purified protein and 2 mU of guinea pig liver TG2 (Sigma, St. Louis, MO, USA) (Kaartinen et al., 2002). Purified proteins were kindly provided by Dr. A. Veis from Northwestern University, Chicago, IL (rat tooth DPP), Dr. A. George from Northwestern University, Chicago, IL (recombinant rat DMP1), and Dr. W.T. Butler from the University of Texas, Houston (rat tooth DSP).

Western Blotting of Tooth Extracts and Identification of Crosslinked Proteins
G1-, E-, and G2-extracts (10 µg protein each) from rat teeth were separated on 10% SDS-acrylamide gels under reducing conditions and subsequently transferred onto polyvinyldifluoride membranes. Western blotting was conducted as described previously for bone extracts (Kaartinen et al., 2002), with the following rabbit polyclonal antibodies in TBS-Tween 20: anti-DPP (raised against the C-terminal 245 residues of recombinant rat DSPP, courtesy of Dr. A. Veis), anti-DSPP (raised against mouse DSPP, courtesy of Dr. M. MacDougall from the University of Texas Health Sciences Center, San Antonio), anti-DSP (raised against rat DSP, courtesy of Dr. W.T. Butler), anti-DMP1 (raised against rat recombinant DMP1, courtesy of Dr. A. George), and anti-BSP (LF-100, courtesy of Dr. L.W. Fisher from the NIDCR, Bethesda, MD). TG2 was detected with the use of monoclonal anti-TG2 antibody (CB7402/TG100; Labvision/Neomarkers, Fremont, CA, USA).

Immunohistochemistry
For light microscopy and immunohistochemistry, one-month-old rat hemimandibles were fixed by overnight immersion at 4°C in periodate-lysine-paraformaldehyde fixative (2% paraformaldehyde, 0.075 mol/L lysine, and 0.01 mol/L sodium periodate, pH 6.8). This was followed by decalcification in 4.13% EDTA and dehydration; samples were embedded in paraffin and processed for immunohistochemistry as described previously (Kaartinen et al., 2002). Five-µm-thick tissue sections were stained with rabbit polyclonal anti-DMP1 (courtesy of Dr. W.T. Butler), anti-DPP and anti-BSP (LF-100), and mouse monoclonal anti-TG2 (Labvision/Neomarkers), as primary antibodies, followed by appropriate secondary biotinylated antibody (Caltag Laboratories, Burlingame, CA, USA). Sections were counterstained with methyl green. In all cases, control incubations consisted of identical procedures except for omission of the primary antibody, and these incubations showed a complete absence of immunoreaction product.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS & METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Transglutaminase Activity and Substrates in Extracts of Rat Teeth
The TG activity assay, which detects biotin-linked primary amine incorporation into TG substrates extracted from teeth and separated by SDS-PAGE (Fig. 1AGo), showed abundant endogenous TG activity in the tooth E-extracts. This was demonstrated by the incorporation of the labeled amine into proteins having molecular weights of 60, 80, 100, and > 150 kDa (high-molecular-weight [HMW] region). The band at 100 kDa represents incorporation of the label directly into the TG enzyme itself. Purification of the biotin-labeled material by avidin-affinity chromatography (Fig. 1BGo) resulted in purification of bands found at 60, 80, and 100 kDa (TG2), but a loss of the HMW material. Conventional N-terminal sequencing of this preparation revealed the N-terminal DPP sequence Asp-Asp-Pro-Asn. While DPP does not contain glutamine residues, and is therefore not labeled in this TG-primary amine reaction, it nevertheless co-purified either bound or crosslinked to other substrate proteins, or to the TG2 enzyme itself, in the preparation, although our attempts to immunodetect it were unsuccessful. Further characterization of the preparation with antibodies against other SIBLING proteins (OPN, BSP, DSP, DSPP, and DMP1) showed strong immunoreactivity only for BSP at an 80-kDa band (Fig. 1BGo), and faint staining for DMP1 with a band of ~ 60 kDa.



View larger version (40K):
[in this window]
[in a new window]
  		Figure 1. Transglutaminase (TG) activity and protein substrates in tooth EDTA extracts. (A) Western blotting TG-activity assay; 5(biotin)pentylamine (bPA) labeling of tooth substrates by endogenous TG in tooth EDTA extract (E). bPA incorporation is detected by ExtrAvidin®-HRP conjugate and occurs in proteins having molecular weights of 60 and 80 kDa, and high-molecular-weight material above 150 kDa. The band at 100 kDa in the last lane represents TG2 itself, which autolabels in the crosslinking reaction. (B) Purification of bPA-labeled material by avidin chromatography and detection of BSP and DMP1 in the preparation by Western blotting with anti-BSP and anti-DMP1 antibodies; N-terminal sequencing gave the DPP sequence Asp-Asp-Pro-Asn. EAvid, ExtrAvidin®-HRP conjugate.

 
High-molecular-weight SIBLING Proteins in Teeth
The initial identification of DPP, DMP1, and BSP as potential TG substrates in the tooth extracts led us to search for HMW polymers of these and other SIBLING proteins as an indication of crosslinking by TGs in vivo. For this, tooth extract samples (G1, E, and G2) were boiled in mercaptoethanol, and proteins were electrophoretically separated under reducing conditions to prevent thiol-bridging in the case of DPP and DSP, which contain cysteine residues (not contained in other SIBLING proteins). Immunoblotting of these samples for DPP revealed the presence of HMW DPP in the G2-extract—a preparation whose extraction conditions generally obtain proteins strongly bound to collagen (Fig. 2AGo) and which are not removed in the G1-extract. This HMW DPP cannot be DSPP (the precursor of DPP and DSP; MacDougall et al., 1997), since DSPP was found exclusively in the E-extract (Fig. 2BGo). While the absence of glutamine residues in DPP prevents it from forming homotypic DPP-DPP polymers via TG crosslinking, DPP could provide the lysines for crosslink formation if suitable glutamine-donor protein partners were available. In fact, the TG2 enzyme itself can serve as such a binding partner (Lorand and Graham, 2003), and in our work, incubation of the DPP protein with TG2 (Fig. 2CGo) and detection with the DPP antibody showed the formation of HMW DPP polymers. Further characterization of this material with use of the TG2 antibody revealed polymeric forms of TG2 (Fig. 2DGo) after incubation with DPP. The enzyme preparation used in this study (guinea pig liver TG2) has two active forms, at 100 kDa and at 75 kDa—the monoclonal antibody used in this study detects the 75-kDa TG2. It is also possible that the HMW DPP found in the G2-extract represents covalent complexes with other, as-yet-unidentified, crosslinking partners. The TableGo shows a summary of these biochemical data.



View larger version (31K):
[in this window]
[in a new window]
  		Figure 2. High-molecular-weight forms of SIBLING proteins in teeth and crosslinking by TG-Western blot analysis. (A) DPP polymers are present in the G2-extract. (B) DSPP, precursor protein for DPP and DSP, is found only in the E-extract. (C) Purified DPP forms polymers in vitro after TG2 incubation. (D) TG2 is found in HMW forms after incubation with DPP, indicating that it can serve as a crosslinking partner for DPP. (E) DMP1 polymers are found in both E- and G2-extracts. (F) Polymer formation of DMP1 after incubation with TG2, and bPA incorporation into DMP1 after TG2 incubation. (G) DSP is found only in monomeric forms in the E-extract. (H) DSP forms polymers and incorporates bPA when incubated with TG2. (I) BSP ‘dimers’ are found in both the E- and G2-extracts; similar-sized BSP forms are also found in rat and mouse bone E-extracts.

 

View this table:
[in this window]
[in a new window]
  		Table. SIBLING Proteins as Substrates for Transglutaminase
 
TG2 and SIBLING Co-localization at Cell-Matrix Adhesion Sites
Localization of TG2 in teeth by immunohistochemistry revealed strong immunostaining in the predentin and along dentinal tubules (Fig. 3AGo), and in the pericellular matrix surrounding cementocytes in cellular cementum of molars (Fig. 3BGo). Immunostaining for DPP was strong throughout the dentin and along dentinal tubules (Fig. 3AGo), whereas DMP1 staining was found only along the tubules in dentin (Fig. 3AGo) and in the pericellular matrix of cementocytes in cellular cementum of molars (Fig. 3BGo). BSP was localized mainly to the predentin and odontoblasts (Fig. 3AGo) and to cementoblasts in cellular cementum (Fig. 3BGo).



View larger version (81K):
[in this window]
[in a new window]
  		Figure 3. Immunohistochemical localization of SIBLING proteins in rat teeth. (A) TG2 and SIBLING proteins co-localize in predentin (TG2 and BSP) and along dentinal tubules (TG2, DPP, and DMP1), as represented by red/pink immunoreactivity over these tissue structures. DPP shows additional immunostaining of the intertubular dentin. (B) Immunostaining of cementocytes and their pericellular matrix in cellular cementum of molars. Od, odontoblast; PD, predentin; DEN, dentin; DT, dentinal tubules; Cc, cementocytes. Magnification bars equal 50 µm.

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS & METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
DPP and DMP1 Polymers
This study describes TG activity, TG2 localization, and analyses of SIBLING proteins as substrates for TG in rat teeth. Based on the present data for teeth, and on previous data for cartilage and bone, we report here two novel substrates for TG2 in mineralized tissues, DPP and DMP1. Like the bone-substrate proteins BSP and OPN, both DPP and DMP1 belong to the SIBLING protein family, as classified by Fisher and Fedarko (2003). Divalent ion-dependent self-assembly of DPP has been described previously (Stetler-Stevenson and Veis, 1987; Marsh, 1989). Such DPP macromolecular assemblies may be additionally crosslinked to other ECM components. In fact, our observation that glutamine-lacking DPP co-purifies by avidin chromatography with the labeled material is an indication that it can be crosslinked to other proteins via its lysines. The requirement for harsh extraction conditions to obtain DPP polymers (second guanidium-HCl extraction of the collagen-enriched residue) suggests that HMW DPP may have a non-covalent interaction with the collagen framework, which could represent an initial assembly step prior to TG-mediated crosslinking. Indeed, a DPP-collagen triple-helix interaction has been described (Stetler-Stevenson and Veis, 1986; Dahl et al., 1998) at the 680- to 750-amino-acid region in triple-helical type I collagen (Dahl et al., 1998). While the binding site was not resolved at the level of the specific {alpha}-chains, interestingly, this site in the collagen {alpha}2(I) chain harbors two RGD sequences and one glutamine residue, the latter of which could potentially serve as the donor residue for crosslink formation with DPP lysine residues.

Recently, DMP1 has been reported to form calcium-ion-dependent self-assemblies, which promote mineral nucleation (He et al., 2003). Qin and co-workers (2001) have described DMP1 (100 kDa as the full-length protein) at molecular weights above 150 kDa in purified dentin and in bone protein preparations, providing additional data consistent with our observation that DMP1 is further processed into HMW forms by TG activity. The antibody used by Qin et al.(2001) to identify HMW DMP1 was generated against a C-terminal 57-kDa fragment of DMP1, thus implicating this region in the formation of the HMW complexes. This C-terminal portion of DMP1 is also responsible for its ability to nucleate mineral (Tartaix et al., 2004). In our study, the presence of HMW DMP1 in the demineralizing E-extract indicates its association with the mineral phase and is consistent with its role as a mineral nucleator (He at al., 2003). The additional existence of HMW DMP1 in the G2-extract implies that it has affinity for insoluble ECM scaffold proteins such as collagen. At this time, it is not known whether DMP1 is crosslinked with DPP (both in the G2-extract) along the dentinal tubules, where they co-localize with TG2.

Polymerized SIBLINGs—Cell Adhesion Forms?
TG2 co-localizes with DPP, DMP1, and BSP at cell-matrix interfaces in teeth. It has long been speculated that the mineral-binding proteins typical of calcified tissues accumulate at these sites to inhibit mineralization and/or to signal from the ECM to the cells (McKee and Nanci, 1996). SIBLING proteins typically are subjected to several post-translational modifications affecting their function and interactions with other ECM components. For example, it has been shown that DMP1 requires proteolytic cleavage to be activated from a mineralization inhibitor to a mineral nucleator (57-kDa form) (Tartaix et al., 2004), and that phosphorylation of OPN is critical for its ability to bind to crystal surfaces and inhibit mineral formation (Jono et al., 2000). Based on reports demonstrating the role of TG2 in cell adhesion and its close spatial association with ß1 and ß3 integrins on the cell surface (Akimov et al., 2000), it is possible that HMW polymer forms of RGD-containing SIBLING proteins form when bound to integrins linked to TG2. Such an RGD- and TG2-mediated protein polymerization mechanism could promote integrin clustering, and thus participate in cell-matrix adhesion and/or intracellular signaling pathways. As further evidence of the role of polymerization and cell adhesion, it is noteworthy to mention that several RGD proteins—including type I collagen, fibronectin, laminin, nidogen, BSP, OPN, fibrillin-1, and microfibril-associated glycoprotein (Lorand and Graham, 2003)—as well as the SIBLING substrates from the tooth described here, all act as TG2 substrates. Moreover, TG2-mediated fibrillogenesis of fibronectin can be inhibited by both RGD peptides and by ß1 integrin antibodies, thus showing a clear link between crosslinking and integrin-binding (Darribère et al., 1990). Consistent with these observations, we have shown here that DPP, which is localized to the odontoblast-matrix interface and has no glutamine residues but an RGD sequence, is clearly found in HMW forms, and thus is potentially crosslinked by TG2 in vivo. Conversely, DSP, which is also located at the same cell-adhesion sites (D’Souza et al., 1992) and has glutamine residues but no RGD sequence, does not become crosslinked in vivo (data summarized in the TableGo). However, as shown in the present study, purified DSP experimentally incubated with TG2 in vitro readily forms polymers. In conclusion, HMW protein polymers found in bones and teeth could represent ‘activated’ cell adhesion forms of SIBLING proteins in mineralized tissues (TableGo). A similar activation process may function in non-mineralizing tissues such as salivary glands and tumors, where SIBLING proteins are also highly expressed (Lee et al., 1996; Ogbureke and Fisher, 2004).


   ACKNOWLEDGMENTS
 
We thank our collaborators for generously donating antibodies and proteins for this study, and Dr. Younan Liu for his excellent technical assistance. This study was supported by operating grants from the CIHR to MTK (MOP-62713) and MDM (MT-11360).

Received January 27, 2005; Last revision April 19, 2005; Accepted April 26, 2005


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS & METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Aeschlimann D, Mosher D, Paulsson M (1996). Tissue transglutaminase and factor XIII in cartilage and bone remodeling. Semin Thromb Hemost 22:437–443.[Medline]

Akimov SS, Krylov D, Fleischman LF, Belkin AM (2000). Tissue transglutaminase is an integrin-binding adhesion coreceptor for fibronectin. J Cell Biol 148:825–838.[Abstract/Free Full Text]

D’Souza RN, Bronckers AL, Happonen RP, Doga DA, Farach-Carson MC, Butler WT (1992). Developmental expression of a 53 KD dentin sialoprotein in rat tooth organs. J Histochem Cytochem 40:359–366.[Abstract]

Dahl T, Sabsay B, Veis A (1998). Type I collagen-phosphophoryn interactions: specificity of the monomer-monomer binding. J Struct Biol 123:162–168.[ISI][Medline]

Darribère T, Guida K, Larjava H, Johnson KE, Yamada KM, Thiery JP, et al. (1990). In vivo analyses of integrin beta 1 subunit function in fibronectin matrix assembly. J Cell Biol 110:1813–1823.[Abstract/Free Full Text]

Esposito C, Caputo I (2005). Mammalian transglutaminases. Identification of substrates as a key physiological function and physiopathological relevance. FEBS J 272:615–631.

Fisher LW, Fedarko NS (2003). Six genes expressed in bones and teeth encode the current members of the SIBLING family of proteins. Connect Tissue Res 44(S1):33–40.

Goldberg HA, Domenicucci C, Pringle GA, Sodek J (1988). Mineral-binding proteoglycans of fetal porcine calvarial bone. J Biol Chem 263:12092–12101.[Abstract/Free Full Text]

Goldsmith HL, Labrosse JM, McIntosh FA, Mäenpää PH, Kaartinen MT, McKee MD (2002). Homotypic interactions of soluble and immobilized osteopontin. Ann Biomed Eng 30:840–850.[Medline]

Gorski JP, Kremer EA, Chen Y, Ryan S, Fullenkamp C, Delviscio J, et al. (1997). Bone acidic glycoprotein-75 self-associates to form macromolecular complexes in vitro and in vivo with the potential to sequester phosphate ions. J Cell Biochem 64:547–564.[Medline]

He G, Dahl T, Veis A, George A (2003). Nucleation of apatite crystals in vitro by self-assembled dentin matrix protein 1. Nat Mater 2:552–558.[ISI][Medline]

Heath DJ, Downes S, Verderio E, Griffin M (2001). Characterization of tissue transglutaminase in human osteoblast-like cells. J Bone Miner Res 16:1477–1485.[Medline]

Johnson K, Hashimoto S, Lotz M, Pritzker K, Terkeltaub R (2001). Interleukin-1 induces promineralizing activity of cartilage tissue transglutaminase and Factor XIIIa. Am J Pathol 159:149–163.[Abstract/Free Full Text]

Jono S, Peinado C, Giachelli CM (2000). Phosphorylation of osteopontin is required for inhibition of vascular smooth muscle cell calcification. J Biol Chem 275:20197–20203.[Abstract/Free Full Text]

Kaartinen MT, Pirhonen A, Linnala-Kankkunen A, Mäenpää PH (1999). Cross-linking of osteopontin by tissue transglutaminase increases its collagen binding properties. J Biol Chem 274:1729–1735.[Abstract/Free Full Text]

Kaartinen MT, El-Maadawy S, Räsänen NH, McKee MD (2002). Tissue transglutaminase and its substrates in bone. J Bone Miner Res 12:2161–2173.

Lee CH, Lee SK, Chi JG, Park SC, Chung SI, Saitoh M, et al. (1996). Immunohistochemical evaluation of transglutaminase C in tumours of salivary glands. Eur J Cancer B Oral Oncol 32(B):401–406.

Lorand L, Graham RM (2003). Transglutaminases: crosslinking enzymes with pleiotropic functions. Nat Rev Mol Cell Biol 4:140–156.[ISI][Medline]

MacDougall M, Simmons D, Luan X, Nydegger J, Feng J, Gu TT (1997). Dentin phosphoprotein and dentin sialoprotein are cleavage products expressed from a single transcript coded by a gene on human chromosome 4. Dentin phosphoprotein DNA sequence determination. J Biol Chem 272:835–842.[Abstract/Free Full Text]

Marsh ME (1989). Self-association of calcium and magnesium complexes of dentin phosphophoryn. Biochemistry 28:339–345.[Medline]

McKee MD, Nanci A (1996). Osteopontin at mineralized tissue interfaces in bone, teeth and osseointegrated implants: ultrastructural distribution and implications for mineralized tissue formation, turnover and repair. Microsc Res Tech 33:141–164.[Medline]

Nurminskaya M, Magee C, Faverman L, Linsenmayer TF (2003). Chondrocyte-derived transglutaminase promotes maturation of preosteoblasts in periosteal bone. Dev Biol 263:139–152.[ISI][Medline]

Ogbureke KU, Fisher LW (2004). Expression of SIBLINGs and their partner MMPs in salivary glands. J Dent Res 83:664–670.[Abstract/Free Full Text]

Qin C, Brunn JC, Jones J, George A, Ramachandran A, Gorski J, et al. (2001). A comparative study of sialic acid-rich proteins in rat bone and dentin. Eur J Oral Sci 109:133–141.[ISI][Medline]

Stetler-Stevenson WQ, Veis A (1983). Bovine dentin phosphophoryn: composition and molecular weight. Biochemistry 22:4326–4335.[Medline]

Stetler-Stevenson WQ, Veis A (1986). Type I collagen shows a specific binding affinity for bovine dentin phosphophoryn. Calcif Tissue Int 38:135–141.[ISI][Medline]

Stetler-Stevenson WQ, Veis A (1987). Bovine dentin phosphophoryn: calcium ion binding properties of high molecular weight preparation. Calcif Tissue Int 40:97–102.[ISI][Medline]

Tartaix PH, Doulaverakis M, George A, Fisher LW, Butler WT, Qin C, et al. (2004). In vitro effects of dentin matrix protein-1 on hydroxyapatite formation provide insights into in vivo functions. J Biol Chem 279:18115–18120.[Abstract/Free Full Text]




This article has been cited by other articles:


Home page
 J. Histochem. Cytochem.Home page
Y. Nakano, H. F. Al-Jallad, A. Mousa, and M. T. Kaartinen
Expression and Localization of Plasma Transglutaminase Factor XIIIA in Bone
J. Histochem. Cytochem., July 1, 2007; 55(7): 675 - 685.
[Abstract] [Full Text] [PDF]

Home page
 J. Histochem. Cytochem.Home page
M. T. Kaartinen, M. Murshed, G. Karsenty, and M. D. McKee
Osteopontin Upregulation and Polymerization by Transglutaminase 2 in Calcified Arteries of Matrix Gla Protein-deficient Mice
J. Histochem. Cytochem., April 1, 2007; 55(4): 375 - 386.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (9)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kaartinen, M.T.
Right arrow Articles by McKee, M.D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kaartinen, M.T.
Right arrow Articles by McKee, M.D.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
IADR Journals Advances in Dental Research ®
Journal of Dental Research ® Critical Reviews (1990-2004)