Methylglyoxal Inhibits the Binding Step of Collagen Phagocytosis

Bacterial infection-induced fibrosis affects a wide variety of tissues, including the periodontium, but the mechanisms that dysregulate matrix turnover and mediate fibrosis are not defined. Since collagen turnover by phagocytosis is an important pathway for matrix remodeling, we studied the effect of the bacterial and eukaryotic cell metabolite, methylglyoxal (MGO), on the binding step of phagocytosis by periodontal fibroblasts. Type 1 collagen was treated with various concentrations of methylglyoxal, an important glucose metabolite that modifies Arg and Lys residues. The extent of MGO-induced modifications was authenticated by amino acid analysis, solubility, and cross-linking. Cells were incubated with fluorescent beads coated with collagen, and the percentage of phagocytic cells was estimated by flow cytometry. MGO inhibited collagen binding (20% of control for 10 mm MGO) in a time- and concentration-dependent manner. MGO-induced inhibition of binding was prevented by aminoguanidine, which blocks the formation of collagen cross-links. MGO reduced collagen binding strength and blocked intracellular calcium signaling. MGO modified the Arg residue in the critical α2β1 integrin-binding recognition sequence of triple helical collagen peptides, whereas MGO-induced cross-linking of Lys residues played only a small role in binding inhibition. Thus, MGO modifications of Arg residues in collagen could be a key factor in the impaired degradation of collagen that promotes fibrosis in chronic infections, such as periodontitis. Bacterial infection-induced fibrosis affects a wide variety of tissues, including the periodontium, but the mechanisms that dysregulate matrix turnover and mediate fibrosis are not defined. Since collagen turnover by phagocytosis is an important pathway for matrix remodeling, we studied the effect of the bacterial and eukaryotic cell metabolite, methylglyoxal (MGO), on the binding step of phagocytosis by periodontal fibroblasts. Type 1 collagen was treated with various concentrations of methylglyoxal, an important glucose metabolite that modifies Arg and Lys residues. The extent of MGO-induced modifications was authenticated by amino acid analysis, solubility, and cross-linking. Cells were incubated with fluorescent beads coated with collagen, and the percentage of phagocytic cells was estimated by flow cytometry. MGO inhibited collagen binding (20% of control for 10 mm MGO) in a time- and concentration-dependent manner. MGO-induced inhibition of binding was prevented by aminoguanidine, which blocks the formation of collagen cross-links. MGO reduced collagen binding strength and blocked intracellular calcium signaling. MGO modified the Arg residue in the critical α2β1 integrin-binding recognition sequence of triple helical collagen peptides, whereas MGO-induced cross-linking of Lys residues played only a small role in binding inhibition. Thus, MGO modifications of Arg residues in collagen could be a key factor in the impaired degradation of collagen that promotes fibrosis in chronic infections, such as periodontitis. Connective tissue homeostasis is maintained by fibroblasts that can synthesize and degrade the collagenous matrix in response to changes in physiological and pathological conditions. Disruptions to the balance of matrix remodeling may lead to net loss of collagen or to disorganized overgrowth of collagen in several pathological conditions (1Birkedal-Hansen H. Moore W.G. Bodden M.K. Windsor L.J. Birkedal-Hansen B. DeCarlo A. Engler J.A. Crit. Rev. Oral Biol. Med. 1993; 4: 197-250Crossref PubMed Scopus (2639) Google Scholar). In chronic infections of connective tissues, such as periodontitis, bacterial cell metabolites (2Ferguson G.P. Booth I.R. J. Bacteriol. 1998; 180: 4314-4318Crossref PubMed Google Scholar) disrupt matrix homeostasis and promote collagen loss and fibrosis in collagen-rich tissues (1Birkedal-Hansen H. Moore W.G. Bodden M.K. Windsor L.J. Birkedal-Hansen B. DeCarlo A. Engler J.A. Crit. Rev. Oral Biol. Med. 1993; 4: 197-250Crossref PubMed Scopus (2639) Google Scholar). At least part of this loss of homeostasis has been attributed to infection-induced increase of collagen synthesis and impaired collagen degradation (3Moskow B.S. Polson A.M. J. Clin. Periodontol. 1991; 18: 534-542Crossref PubMed Scopus (32) Google Scholar, 4Chou D.H. Lee W. McCulloch C.A. J. Immunol. 1996; 156: 4354-4362PubMed Google Scholar). Although an intracellular phagocytic pathway of collagen degradation by fibroblasts is known to be important for maintaining homeostasis in mature connective tissues (5Everts V. van der Zee E. Creemers L. Beertsen W. Histochem. J. 1996; 28: 229-245Crossref PubMed Scopus (284) Google Scholar), the effect of bacterial and eukaryotic cell metabolites on collagen phagocytosis has not been defined. The recognition and binding of collagen molecules by cell surface receptors is the initial, rate-limiting step in collagen phagocytosis by fibroblasts. The principal receptor for type I fibrillar collagen is the α2β1 integrin (6Gullberg D. Gehlsen K.R. Turner D.C. Ahlen K. Zijenah L.S. Barnes M.J. Rubin K. EMBO J. 1992; 11: 3865-3873Crossref PubMed Scopus (207) Google Scholar, 7Kern A. Eble J. Golbik R. Kuhn K. Eur. J. Biochem. 1993; 215: 151-159Crossref PubMed Scopus (181) Google Scholar, 8Kapyla J. Ivaska J. Riikonen R. Nykvist P. Pentikainen O. Johnson M. Heino J. J. Biol. 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Barnes M.J. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, D.J. Barnes M.J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar, Barnes M.J. J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus Google Scholar). of collagen to bacterial and eukaryotic cell glucose metabolites affects collagen by that can the of connective tissues and matrix turnover L. 1998; PubMed Scopus Google Scholar). MGO has been in the infections J. Clin. Periodontol. PubMed Scopus Google Scholar), but the effect of MGO-induced modifications on the binding and of collagen phagocytosis on the α2β1 has not been a role for phagocytosis in of connective tissues, we the effect of MGO of collagen on the α2β1 binding step of collagen Since collagen turnover in periodontal connective tissues is in tissue studied J. J.M. PubMed Scopus Google Scholar) and periodontal fibroblasts the α2β1 integrin W. J. McCulloch C.A. J. 1996; PubMed Scopus Google Scholar), we cells the as a for the rate-limiting in collagen we that MGO-induced modifications of the in collagen the collagen binding step of a that chronic bacterial in to connective tissues collagen to loss of connective tissue beads were to MGO aminoguanidine, and were was beads were helical collagen amino the α2β1 integrin binding of collagen were Bacterial was integrin and to integrin were integrin was to the receptor 1 was to integrin was to integrin was to was The was and fibroblasts were as McCulloch C.A. J. 1991; PubMed Google Scholar). Cells were in and maintained in a and were with fibroblasts Type were and incubated in modified and receptor and fibroblasts by W. of were with 1 mm and in as of MGO-induced of tissues in of and were and with and were for The were with to the of the the of beads were as W. J. McCulloch C.A. J. 1996; PubMed Scopus Google Scholar). beads were incubated with 1 of an of type I collagen with of 1 to to formation on the and incubated for 10 is known to formation on the beads M. J. McCulloch C.A. J. 1991; PubMed Google Scholar). beads were by beads with 1 of for The beads were incubated with control or in for 10 and incubated in a was treated with or 10 mm MGO in or to In collagen was with for to collagen was in in for the beads were with in and to with of of collagen on beads was by of collagen as C.A. P.D. Lee W. L. H. J. McCulloch C.A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). of were were coated on of MGO-induced cross-linking was by of beads of of cross-linking MGO was estimated by of of collagen by of in by amino acid for mm mm was to beads or were by beads to for and the were by by and were and collagen beads fluorescent were on to the of cells a of beads with cells for cells were with and in a that beads M. McCulloch C.A. PubMed Scopus Google Scholar, Lee W. P.D. M. McCulloch C.A. J. PubMed Google Scholar). of cells were for binding by flow to the percentage of cells with fluorescent beads and the of beads or cells were with or incubated with beads for 1 with and by flow cytometry. for and integrin or was to and flow as D.H. Lee W. McCulloch C.A. J. Immunol. 1996; 156: 4354-4362PubMed Google Scholar). of collagen was as (11Arora P.D. Glogauer M. Kapus A. Kwiatkowski D.J. McCulloch C.A. Mol. Biol. Cell. PubMed Scopus Google Scholar). beads were incubated for with and was blocked by on beads was by and of and binding strength of collagen beads to cells was estimated by a D.H. Lee W. McCulloch C.A. J. Immunol. 1996; 156: 4354-4362PubMed Google Scholar, Lee W. E. McCulloch C.A. PubMed Scopus Google Scholar) in which binding of beads to cells was in Cells in were incubated with control or beads for 1 and to of with 1 to with a Cells were with for with with with and were to the of and the of beads with cell was by in a wide in the of the least cells were in and were for The was with the cells to the of the to of the the cell The on the cells can be for by the of an on a to D.J. J. 2000; Scopus Google Scholar), the the which the the cell to a by the 1 In this the is the the is the is the and is the is the a of the D.J. J. 2000; Scopus Google Scholar). In the was the flow was was estimated to be 10 and were of Thus, and in a of I fibrillar were treated with MGO or with control Cells were and for and with with with and with Cells were and and were with Cells were and surface were by beads were coated with collagen and with were to cells that were with calcium was with a P.D. McCulloch C.A. J. PubMed Scopus Google Scholar). cells that beads were were type I collagen or for cells were with and with concentrations were with the as a The of were for were on conditions and to were with for integrin or were by including and were as M. P. J. McCulloch C.A. J. PubMed Google Scholar). control and beads were to cells for 1 was and the cells were to Cells and beads were with mm mm 10 mm and 1 beads were with a with and and were in were and to concentrations in in the of were and were by as of beads were incubated with were incubated on and cross-linking was by a of and by The beads were and of collagen beads with cells was as to flow of MGO-induced of beads were treated with to MGO-induced cross-linking. beads were incubated with MGO In was by beads to MGO binding were as by with flow cytometry. beads treated with as helical collagen the α2β1 integrin binding of collagen of were in and treated with 10 mm was and in mm was to for The was with mm to an of The was to to and on a with a for were least and and were were or factor of by for was incubated collagen with MGO J. Biochem. Biol. 1999; PubMed Scopus Google Scholar) for or with for to A. PubMed Scopus Google Scholar, A. A. PubMed Scopus Google Scholar). of collagen with of inhibited collagen binding to cells of but with MGO were of for 1 mm of for 10 mm were with collagen, the were and of the MGO of collagen to beads was by amino acid of collagen concentrations of were reduced of Arg to Since MGO of Arg that to J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar), we which with concentrations of The of collagen was by by of in the of control collagen was whereas collagen and 10 of the that was in was with concentrations of MGO analysis, we for of collagen molecules MGO which is of collagen cross-linking or to MGO of in a tissue or for MGO with a to of the connective tissues to periodontal but not in tissues of of collagen reduced collagen binding to cells to of control and this effect was MGO were not to a loss of collagen of collagen by C.A. P.D. Lee W. L. H. J. McCulloch C.A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) of collagen, of MGO of in collagen of in collagen by MGO Cells were incubated with beads to the of the MGO were of cells that beads MGO of beads effect on the of cells with collagen binding was in fibroblasts as fibroblasts estimated collagen strength by the of cells that beads cells were incubated with beads (11Arora P.D. Glogauer M. Kapus A. Kwiatkowski D.J. McCulloch C.A. Mol. Biol. Cell. PubMed Scopus Google Scholar), cells a of collagen binding in that cells but a small could or in the of collagen receptors in the cell of fibroblasts incubated with control beads of cells with beads with to which binding of only that MGO may the binding strength of collagen receptors or that collagen beads may to control this binding is inhibited by in we beads to control and MGO conditions. At concentrations of beads that the conditions but the of for collagen beads was by flow 10 mm collagen the was as the of the cells to collagen beads incubated beads with cells of and was of binding were of not that collagen receptors are not a to the effect of MGO modifications on collagen we estimated the strength of cell binding to collagen D.H. Lee W. McCulloch C.A. J. Immunol. 1996; 156: 4354-4362PubMed Google Scholar, Lee W. E. McCulloch C.A. PubMed Scopus Google Scholar). an of cells incubated with control beads of beads a In collagen beads were beads were a the effect of MGO on collagen binding could be by of collagen with small of the percentage of cells binding collagen beads were the that the effect of MGO on collagen binding is of collagen binding was by collagen Cells incubated with of beads reduced binding as a of MGO The inhibition of collagen binding by MGO was on the of cell with was inhibition of binding of MGO on collagen of binding of in a inhibition of collagen binding was a of MGO-induced collagen is a that blocks the formation of collagen M. H. A. P. A. PubMed Scopus Google Scholar, P. A. PubMed Scopus Google Scholar). of collagen beads with MGO and aminoguanidine, collagen binding was of control for 1 mm MGO and for 10 mm are of with MGO and is for phagocytosis and intracellular of collagen P.D. G.P. J. McCulloch C.A. J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus Google Scholar), a of phagocytosis that can be by cell in (11Arora P.D. Glogauer M. Kapus A. Kwiatkowski D.J. McCulloch C.A. Mol. Biol. Cell. PubMed Scopus Google Scholar). and of cell to control or we cell by cell surface in with Cells were and of the surface on with control The reduced of cells on was not to cell cells on control the of cells collagen intracellular calcium is or binding is inhibited P.D. L. B. J. McCulloch C.A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Since matrix can intracellular calcium in cells J. PubMed Scopus Google Scholar), we collagen binding to In control collagen beads cells in we a increase of with an increase of with to a P.D. L. B. J. McCulloch C.A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In cells that collagen beads cells in increase of collagen with effect was not to cell the MGO to the collagen, cells on tissue of that were to a cells that were incubated with beads increase of not to collagen we of but effect of the MGO on the binding to collagen, fibroblasts the which is in (5Everts V. van der Zee E. Creemers L. Beertsen W. Histochem. J. 1996; 28: 229-245Crossref PubMed Scopus (284) Google Scholar). The effect of MGO on collagen was estimated by cells with beads coated with of collagen was to The of beads in 10 mm collagen was reduced to of control the of collagen beads that to cells were of we for the reduced binding of beads MGO and beads in only cells with cells that or were of beads control and of MGO on collagen of of cells with collagen beads for of cells with collagen beads for in a MGO affects the binding step of collagen phagocytosis but not the we collagen to the collagen receptors that may be by a of collagen cells were and with beads were to integrin and of which are important receptors for fibrillar collagen (6Gullberg D. Gehlsen K.R. Turner D.C. Ahlen K. Zijenah L.S. Barnes M.J. Rubin K. EMBO J. 1992; 11: 3865-3873Crossref PubMed Scopus (207) Google Scholar, W. T. Mol. Cell. Full Text Full Text PDF PubMed Scopus Google Scholar). were was reduced integrin and on an effect that was by concentrations of MGO the of beads that to cells were of with of were on to for the of integrin was but was for the with 1 mm MGO and 10 mm collagen beads that the integrin but not is in binding of collagen to the of the α2β1 integrin in collagen binding by cells with an integrin or integrin to with collagen the of binding of collagen beads was reduced to of control in with W. J. McCulloch C.A. J. 1996; PubMed Scopus Google Scholar), the of the integrin in fibrillar collagen binding by of cells with reduced collagen binding to cells of control 10 mm MGO of collagen reduced binding to of control of collagen beads with the not collagen MGO of collagen beads by with the reduced binding that in with the integrin integrin are this is with of but of the and in phagocytosis by fibroblasts W. J. McCulloch C.A. J. 1996; PubMed Scopus Google Scholar). Since binding could be by collagen we studied the effect of in MGO-induced inhibition of collagen inhibition of cells were with control 1 of by flow only a of inhibition in control and cells of control collagen of control collagen Thus, effect on the effect of MGO on collagen studied the binding inhibition by MGO could be with to the integrin and fibroblasts were incubated with the integrin and for the integrin as D.H. Lee W. McCulloch C.A. J. Immunol. 1996; 156: 4354-4362PubMed Google Scholar) to to collagen Although this binding of collagen was of collagen binding of the integrin and collagen collagen binding of of cell of cell of cell and of cell that the MGO effect could not be by collagen receptor effect was by fibroblasts that were incubated with collagen or collagen beads and with an in that is on binding J.A. S.K. M.J. PubMed Scopus Google Scholar). In cells incubated with collagen beads and was the collagen beads that was not in cells incubated with beads of MGO cross-linking of collagen molecules by of to Arg and Lys residues J. Biochem. Biol. 1999; PubMed Scopus Google Scholar), we the effect of collagen cross-linking by collagen coated beads to a which with the of Arg with inhibited collagen binding in fibroblasts by not as as MGO collagen control of cell 1 mm MGO of cell 10 mm of cell the effect of MGO-induced cross-linking of Lys residues by beads with a that Lys residues with beads with and treated with MGO and incubated with we that of the MGO-induced inhibition of collagen binding was to modifications of Lys residues of cells binding control collagen 10 mm collagen of the by beads an effect on the MGO effect on collagen on the of MGO on the α2β1 integrin binding of fibrillar collagen, we a triple helical collagen that the α2β1 integrin binding D. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). the of this for of collagen phagocytosis by the α2β1 integrin C.A. P.D. Lee W. L. H. J. McCulloch C.A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Arg of which is the α2β1 integrin recognition beads coated with this mm only to cells of cells collagen and MGO reduced this to of the that Arg including the integrin recognition were by binding with MGO of or and the the loss of the modified is with the that are residues of D. M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). could not be was of a Arg residue the the of Arg residues was with that MGO reduced the of of the as by Since the Lys this the of Arg residues in the on collagen of collagen triple helical in a The principal of this is that MGO of collagen the binding step of collagen a critical in maintaining connective tissue homeostasis (5Everts V. van der Zee E. Creemers L. Beertsen W. Histochem. J. 1996; 28: 229-245Crossref PubMed Scopus (284) Google Scholar, J. J.M. PubMed Scopus Google Scholar). Since the and remodeling of collagen-rich tissues, such as the periodontium, is in (1Birkedal-Hansen H. Moore W.G. Bodden M.K. Windsor L.J. Birkedal-Hansen B. DeCarlo A. Engler J.A. Crit. Rev. Oral Biol. Med. 1993; 4: 197-250Crossref PubMed Scopus (2639) Google Scholar, B.S. Polson A.M. J. Clin. Periodontol. 1991; 18: 534-542Crossref PubMed Scopus (32) Google Scholar, V. van der Zee E. Creemers L. Beertsen W. Histochem. J. 1996; 28: 229-245Crossref PubMed Scopus (284) Google Scholar), we that of collagen binding in phagocytic fibroblasts (5Everts V. van der Zee E. Creemers L. Beertsen W. Histochem. J. 1996; 28: 229-245Crossref PubMed Scopus (284) Google Scholar), by bacterial and eukaryotic such as MGO (2Ferguson G.P. Booth I.R. J. Bacteriol. 1998; 180: 4314-4318Crossref PubMed Google Scholar), may connective tissue homeostasis and to MGO is an important metabolite of eukaryotic and bacterial cell (2Ferguson G.P. Booth I.R. J. Bacteriol. 1998; 180: 4314-4318Crossref PubMed Google Scholar) and is in periodontal infections concentrations J. Clin. Periodontol. PubMed Scopus Google Scholar). Since for MGO was only in tissues to we that a of MGO in is to be The concentrations of MGO in the in are and be important to in the MGO is concentrations in pathological J. Clin. Periodontol. PubMed Scopus Google Scholar), MGO can integrin binding D. L. PubMed Scopus Google Scholar). that of collagen with 1 or 10 mm MGO and in of collagen, The MGO-induced formation of the binding step of collagen phagocytosis and is with that only 10 of MGO cell to collagen is reduced J. Biochem. Biol. 1999; PubMed Scopus Google Scholar). (11Arora P.D. Glogauer M. Kapus A. Kwiatkowski D.J. McCulloch C.A. Mol. Biol. Cell. PubMed Scopus Google Scholar, P.D. G.P. J. McCulloch C.A. J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus Google Scholar, W. J. McCulloch C.A. J. 1996; PubMed Scopus Google Scholar), the α2β1 integrin is a critical receptor for the binding step of collagen this was an integrin The effect of MGO on collagen binding was as in binding which in binding with Although we that the receptor 1 R. P. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) may be in the MGO inhibition of collagen cells for in the of inhibition with collagen including K. E. D.J. H. L. K. K. Birkedal-Hansen H. J. Biol. PubMed Scopus Google Scholar), may be in phagocytosis but were not the role of as a receptor may the small of binding that we to collagen in that were with is on and in integrin Rev. Biol. 11: PubMed Scopus Google Scholar). strength reduced may to the collagen binding with In of binding strength with a D.H. Lee W. McCulloch C.A. J. Immunol. 1996; 156: 4354-4362PubMed Google Scholar, Lee W. E. McCulloch C.A. PubMed Scopus Google Scholar), to beads were and by were with of binding of in cells incubated with collagen was binding of beads with control Since MGO collagen to is that MGO may the of collagen collagen by cross-linking. In this integrin binding on the surface of the beads be the surface to of the collagen is the is a for the of collagen binding by and collagen is an important step in phagocytosis and intracellular of collagen J. J.M. PubMed Scopus Google Scholar). that cells on collagen, as J. Biochem. Biol. 1999; PubMed Scopus Google Scholar). the that in of collagen phagocytosis are by intracellular calcium (11Arora P.D. Glogauer M. Kapus A. Kwiatkowski D.J. McCulloch C.A. Mol. Biol. Cell. PubMed Scopus Google Scholar, P.D. L. B. J. McCulloch C.A. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). of cells an of calcium to of matrix but the that this is J. PubMed Scopus Google Scholar, P. A. J. 1999; PubMed Google Scholar). that collagen blocked the of intracellular calcium in cells treated with control collagen with the that MGO collagen recognition and Since integrin is for cell P. E. J. Biol. 1992; PubMed Scopus Google Scholar, H. Crit. Rev. Oral Biol. Med. 1991; PubMed Scopus Google Scholar) and for the collagen binding step of phagocytosis D.H. Lee W. McCulloch C.A. J. Immunol. 1996; 156: 4354-4362PubMed Google Scholar, Lee W. P.D. M. McCulloch C.A. J. PubMed Google Scholar), we that of could MGO the of of that of integrin MGO collagen is by collagen of modifications of critical amino in collagen binding are the of the binding inhibition. with aminoguanidine, a that blocks the formation of collagen by MGO M. H. A. P. A. PubMed Scopus Google Scholar), prevented MGO-induced inhibition of collagen the mechanisms in inhibition of collagen we on the changes by the cross-linking of Lys residues and modifications of Arg residues that are by MGO J. Biochem. Biol. 1999; PubMed Scopus Google Scholar). of collagen by a that modifies Arg residues T. H. J. J. Biol. Chem. Full Text PDF PubMed Google Scholar), inhibited the binding step of collagen the that Arg modifications are important in MGO-induced of collagen The effect on Arg residues was in collagen by the Lys residues with J. J. Biol. Chem. Full Text PDF PubMed Google Scholar) to MGO of Arg residues. The to collagen on collagen binding that were not in which Lys and Arg residues were for The sequence is the principal fibrillar collagen binding for the α2β1 integrin J. Barnes M.J. Cell. 2000; Full Text Full Text PDF PubMed Scopus Google Scholar, D.J. Barnes M.J. J. Biol. Chem. 1998; Full Text Full Text PDF PubMed Scopus Google Scholar, Barnes M.J. J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus Google Scholar) in fibrillar I and and is critical for the binding step of collagen phagocytosis P.D. G.P. J. McCulloch C.A. J. Biol. Chem. 2000; 275: Full Text Full Text PDF PubMed Scopus Google Scholar). a triple helical amino that the α2β1 integrin binding of type I collagen D. J. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) and not Lys residues. we that Arg residues in this sequence were modified by that of Arg residues the critical α2β1 integrin binding of collagen may binding to The to Arg residues by MGO with a of has been D. M. J. Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). MGO modifications Arg residues in the but with for a Arg MGO modifications of Arg residues in the binding sequence of collagen may a effect on the binding of the α2β1 are with that MGO-induced modifications of the sequence of type collagen integrin binding P. PubMed Scopus Google Scholar) and that MGO residues in and integrin-binding of collagen, cell and inhibition of in cells D. L. PubMed Scopus Google Scholar). that MGO of Arg residues in the α2β1 integrin binding of type I collagen molecules collagen binding that is for phagocytosis of collagen Since phagocytosis is an important step for collagen degradation in mature tissues (5Everts V. van der Zee E. Creemers L. Beertsen W. Histochem. J. 1996; 28: 229-245Crossref PubMed Scopus (284) Google Scholar), the binding inhibition the of Arg residues could be in part for the fibrosis that in periodontitis. for of the triple helical collagen and of for of the and are to for with of the and the

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