A chemically modified nonantimicrobial tetracycline (CMT-8) inhibits gingival matrix metalloproteinases, periodontal breakdown, and extra-oral bone loss in ovariectomized rats

被引:51
作者
Golub, LM [1 ]
Ramamurthy, NS
Llavaneras, A
Ryan, ME
Lee, HM
Liu, Y
Bain, S
Sorsa, T
机构
[1] SUNY Stony Brook, Sch Dent Med, Dept Oral Biol & Pathol, Stony Brook, NY 11794 USA
[2] Cent Univ Venezuela, Sch Dent, Dept Pharmacol, Caracas, Venezuela
[3] SkeleTech Inc, Kirkland, WA USA
[4] Univ Helsinki, Inst Dent, Dept Periodontol, Helsinki, Finland
来源
INHIBITION OF MATRIX METALLOPROTEINASES: THERAPEUTIC APPLICATIONS | 1999年 / 878卷
关键词
D O I
10.1111/j.1749-6632.1999.tb07691.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Estrogen deficiency in the postmenopausal (PM) female is the major cause of osteoporosis and may contribute to increased periodontal disease, including alveolar bone loss, seen in these women. In the current study, an animal model of PM osteoporosis, the OVX adult female rat, was studied to determine: (i) the relationship between periodontal breakdown and skeletal bone loss, and (ii) the effect of CMT-8 on gingival collagenase and bone loss. OVX rats were daily gavaged with CMT-8 (1, 2, or 5 mg/rat) for 28 or 90 days; non-OVX rats and those gavaged with vehicle alone served as controls. Elevated collagenase activity, assessed using [H-3-methyl] collagen as substrate in the presence or absence of APMA, was seen in the gingiva of the OVX rats, and CMT-8 therapy suppressed this effect. Western blot revealed a similar pattern for MMP-8 and MMP-13 concentrations. The changes in the gingival collagenase activity paralleled changes in periodontal bone loss, which, in turn, reflected trabecular bone density changes. Preliminary studies on PM humans administered sub-antimicrobial tetracycline as a matrix metalloproteinase Inhibitor are under way.
引用
收藏
页码:290 / 310
页数:21
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