| Project/Area Number |
08672371
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
矯正・小児・社会系歯学
|
|---|
| Research Institution | THE UNIVERSITY OF TOKUSHIMA |
|---|
Principal Investigator |
OHBA Tomoko THE UNIVERSITY OF TOKUSHIMA,UNIVERSITY DENTAL HOSPITAL,RESEARCH ASSOCIATE, 歯学部・附属病院, 助手 (10274242)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MIKI Yoshiki THE UNIVERSITY OF TOKUSHIMA,SCHOOL OF DENTISTRY,RESEARCH ASSOCIATE, 歯学部, 助手 (50294707)
OHBA Yasuo THE UNIVERSITY OF TOKUSHIMA,SCHOOL OF DENTISTRY,RESEARCH ASSOCIATE, 歯学部, 助手 (40294706)
OKADA Kinya THE UNIVERSITY OF TOKUSHIMA,SCHOOL OF DENTISTRY,RESEARCH ASSOCIATE, 歯学部, 助手 (60274239)
TANIMURA Ichirou THE UNIVERSITY OF TOKUSHIMA,SCHOOL OF DENTISTRY,RESEARCH ASSOCIATE, 歯学部, 助手 (20253221)
TAKANO-YAMAMOTO Teruko THE UNIVERSIT OF OKAYAMA,SCHOOL OF DENTISTRY,PROFESSOR, 歯学部, 教授 (00127250)
|
|---|
| Project Period (FY) |
1996 – 1997
|
| Project Status |
Completed (Fiscal Year 1997)
|
| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
|---|
| Keywords | CATHEPSIN L / OSTEOCLAST / BONE RESORPTION / CATHEPSIN L INHIBITOR / EPOXYSUCCINYL PEPTIDE DERIVATIVES |
|---|
| Research Abstract |
In this study we evaluated a series of new synthetic epoxysuccinyl peptide derivatives. Inhibitory effects of these compounds on purified cathepsin L,B,H and J were tested using peptide substrates in vitro and five selected compounds (CLIK-1,63,65,88 and 90) were demonstrated that they were potent inhibitors for cathepsin L.Then, pit formation assay was employed to comfirm inhibitory effects of five compounds on rat osteoclast-mediated bone resorption. CLIK-1 inhibited cathepsin L activity at a concentration of 10^<-6> M,whereas no inhibition of cathepsin B was shown, and at this concentration CLIK-1 significantly suppressed pit formation stimulated by parathyroid hormone. 10^<-7> M of CLIK-63 inhibited cathepsin L activity completely and suppressed pit formation, and remaining activities of cathepsin J was shown but did not inhibit cathepsins B and H at concentrations of 10^<-7> and 10^<-6> M,respectively. CLIK-65 reduced pit formation at concentration of 10^<-7> M at which cathepsin L was inhibited completely and cathepsin J was suppressed moderately, but cathepsin B and H activities were not affected. CLIK-88 and 90 suppressed pit formation at concentrations of 10^<-5> and 10^<-4> M,respectively. At these concentrations, CLIK-88 and 90 completely blocked cathepsin L activity showing no inhibion for cathepsins B and H and weak suppression of cathepsin J.These data indicate that inhibition of cathepsin L in osteoclasts resulted in reduction of osteoclastic bone resorption and inhibitors of cathepsin L are effective at reducing osteoclast-mediated bone resorption. We are going to investigate bone remodeling mechanisms in alveolar bone during orthodintic tooth movement and regulation of root resorption using these new synthetic inhibitors of cathepsin L.
|
