Sequential expressions of MMP-1, TIMP-1, IL-6, and COX-2 genes in induced periapical lesions in rats.
To elucidate the pathogenesis of periapical lesion-associated bone resorption, a disease model of Wistar rat molar was employed. After lesion induction, the mRNAs encoding for matrix metalloproteinase-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2) in the developing lesions were detected by in situ hybridization at day 5, 10, 15 and 20, respectively. At day 5, MMP-1, IL-6 and COX-2 mRNAs appeared predominantly in macrophages. During day 15 to day 20, increased expressions of these mediators were also found in osteoblasts but to a lesser extent compared with those in macrophages. MMP-1 mRNA was also detected in osteoclasts. In contrast, expression of the TIMP-1 gene was noted primarily in osteoblasts and was less pronounced compared with that of MMP-1. The mediator-expressing cells aggregated in the vicinity of bone resorption areas and their numbers increased with time. These data suggest that macrophages and osteoblasts are involved in the development of periapical lesions, and that they promote bone resorption by producing MMP-1, IL-6 and COX-2. In addition, administration of a specific COX-2 inhibitor, meloxicam, reduced the extent of periapical bone resorption by 43% and simultaneously diminished the numbers of cells synthesizing MMP-1 and IL-6 mRNAs. These results further elucidate the significance of COX-2 in disease progression of periapical lesions as it modulates indirectly the production of MMP-1 and IL-6.
Department of Dentistry, National Taiwan University Hospital, Taipei.
Sze-Kwan
SK
Lin
Sang-Hong
SH
Kok
Mark Yen-Ping
MY
Kuo
Tzu-Jou
TJ
Wang
Jeng-Tzung
JT
Wang
Flora Tzu-Chin
FT
Yeh
Michael
M
Hsiao
Wan-Hong
WH
Lan
Chi-Yuan
CY
Hong
D000818:Animals; D001862:Bone Resorption / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D002452:Cell Count; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D017403:In Situ Hybridization; D007274:Injections, Intraperitoneal; D015850:Interleukin-6 / Q000235:genetics*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics*; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D008336:Mandibular Diseases / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D000077239:Meloxicam; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D010483:Periapical Diseases / Q000201:enzymology / Q000235:genetics* / Q000517:prevention & control; D010544:Peroxidases / Q000037:antagonists & inhibitors / Q000235:genetics*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D013843:Thiazines / Q000008:administration & dosage / Q000627:therapeutic use; D013844:Thiazoles / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D000093242:Interleukin-6 Inhibitors
D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D015850:Interleukin-6; D007527:Isoenzymes; D020781:Matrix Metalloproteinase 1; D000077239:Meloxicam; D010544:Peroxidases; D011451:Prostaglandin-Endoperoxide Synthases; D012333:RNA, Messenger; D013843:Thiazines; D013844:Thiazoles; D019715:Tissue Inhibitor of Metalloproteinase-1; D000093242:Interleukin-6 Inhibitors