Targeting and immobilization of bioactive peptides on dentin matrix.
The regeneration of structurally/functionally competent tooth root cementum is a critical step for the successful restoration of periodontal attachment. In this study, we tested whether a poly-glutamic acid-rich domain and glutamine-containing transglutaminase substrate can be used to target biologically active peptides to the mineralized root matrix and to bind such peptides covalently to the organic matrix. As a biologically active model molecule, the integrin-binding motif, RGD, was used. The effects of immobilization of such synthetic peptides to the dentin matrix on cementoblastic adhesion in vitro and cementogenesis in vivo were studied. In vitro, cementoblastic adhesion improved significantly when the dentin surface contained covalently bound peptides. In vivo, this bound peptide significantly increased cementum formation compared with that attained in control conditions. Transglutaminase-catalyzed covalent binding of bioactive peptides targeted to mineralized collagenous dentin matrix via the poly-glutamate domain can be readily achieved. This approach offers potential for clinical use in periodontal regeneration.
Song
J S
JS
Department of Endodontics, School of Dental Medicine, University of Pennsylvania, 240 South 40th Street, Levy Bldg, Rm 423, Philadelphia, PA 19104, USA. jscsong@yahoo.com
Wlodarska
A
A
Ko
H J
HJ
Grzesik
W J
WJ
D000595:Amino Acid Sequence; D002448:Cell Adhesion; D002478:Cells, Cultured; D025021:Cementogenesis / Q000502:physiology*; D003432:Cross-Linking Reagents / Q000378:metabolism; D003739:Dental Cementum / Q000378:metabolism*; D003804:Dentin / Q000378:metabolism*; D016503:Drug Delivery Systems; D005109:Extracellular Matrix / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D016023:Integrins / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D011099:Polyglutamic Acid / Q000378:metabolism; D011485:Protein Binding; D015202:Protein Engineering; D011503:Transglutaminases / Q000378:metabolism
D003432:Cross-Linking Reagents; D006023:Glycoproteins; D016023:Integrins; D009842:Oligopeptides; D011099:Polyglutamic Acid; C047981:arginyl-glycyl-aspartic acid; D011503:Transglutaminases