Characteristic Growth Factor Actions Involved in Periodontal Regeneration

1998 Fiscal Year Final Research Report Summary

• Project/Area Number: 09671950
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Conservative dentistry
• Research Institution: Osaka University
• Principal Investigator: MURAKAMI Shinya Osaka Univ.Fac.of Dentistry Asst. Prof., 歯学部・附属病院, 講師 (70239490)
• Co-Investigator(Kenkyū-buntansha): IKEZAWA Kazuhiro Osaka Univ.Fac.of Dentistry Instructor, 歯学部, 助手 (80294114) ; SHIMABUKURO Yoshio Osaka Univ.Fac.of Dentistry Instructor, 歯学部, 助手 (50231361) ; OKADA Hiroshi Osaka Univ.Fac.of Dentistry Prof. and Chair., 歯学部, 教授 (40038865)
• Project Period (FY): 1997 – 1998
• Keywords: Periodontitis / Periodontal Regeneration / Cementum / Growth Factor / CGF / Heparin Binding IGF-I like Molecule / IGF-I / Periodontal Ligament Cell

Research Abstract

The aim of reriodontal therapy is to regenerate periodontal connective tissues destroyed by periodontitis and restore connective tissue attachment to root surfaces.This requires regeneration of periodontal ligament tissue, alveolar bone and cementum, and integration of new periodontal ligament tissue into bone and cementum.During the course of periodontal regeneration, new cementum formation is essential step because no attchment gain can be accomplished without new cementum.Therefore, we have studied growth factors in cementum which may stimulate the proliferation of periodontal ligament cells and regulate the differentiation into cementblasts.So far, we purified Cementum-derived Growth Factor(CGF) as a major growth factor in cementum and reported CGF has moderate affinity to heparin and its mitogenic activity to fibroblasts is potentiated synergistically in the presence of Epidermal Growth Factor(EGF) or serum factors.This time in the first study, we showed that CGF is an Insulin lik e Growth Factor-I (IGF-I) like molecule but not identical because of some reasons such as different molecular sizes, internal amino acid sequences, mitogenic response to osteoblastic cells, and N-glycosilation.Secondary, we investigated the mechanisms of the synergistic mitogenic effects of CGF and EGF in human fibroblasts by mesuring Cyclin E and Cyclin E dependent kinase activity triggered by both CGF and EGF.The data suggested that high and sustained level of Cyclin E dependent kinase activty may be one important signaling event for the mitogenic synergism induced by both CGF and EGF.Finally, we studied the effects of endogenous IGF-I produced by clonal osteoblastic periodontal ligament cells.We established new mouse clonal cell line which constitutively expresses considerable level of human IGF-I by transfecting human IGF-Ia gene into mouse clonal osteoblastic periodontal ligament cells.This cell line revealed the higher responsiveness to basic Fibroblast Growth Factor (bFGF) and alkaline phosphatase (ALPase) activities than those of the control cell line.Interestingly, these effects by endogenous IGF-I could not be compensated totally by the addition of adequate amount of human recombinant IGF-I.Taken together these results In this report, CGF which is an IGF-I like molecule, and endogenous IGF-I produced by osteoblastic or cementoblastic periodontal ligament cells may play more useful role than exogenous mature IGF-I during the course of periodontal wound healing and regeneration.