Golub L M, Ramamurthy N S, Llavaneras A, Ryan M E, Lee H M, Liu Y, Bain S, Sorsa T
Department of Oral Biology and Pathology, School of Dental Medicine, SUNY at Stony Brook 11794, USA.
Ann N Y Acad Sci. 1999 Jun 30;878:290-310. doi: 10.1111/j.1749-6632.1999.tb07691.x.
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 [3H-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.
绝经后（PM）女性的雌激素缺乏是骨质疏松症的主要原因，并且可能导致这些女性牙周疾病增加，包括牙槽骨丧失。在当前研究中，研究了PM骨质疏松症的动物模型——去卵巢成年雌性大鼠，以确定：（i）牙周破坏与骨骼骨丢失之间的关系，以及（ii）CMT-8对牙龈胶原酶和骨丢失的影响。去卵巢大鼠每天用CMT-8（1、2或5mg/只大鼠）灌胃28天或90天；未去卵巢大鼠和仅用赋形剂灌胃的大鼠作为对照。在去卵巢大鼠的牙龈中观察到胶原酶活性升高，使用[3H-甲基]胶原作为底物在有无APMA的情况下进行评估，并且CMT-8治疗抑制了这种作用。蛋白质印迹显示MMP-8和MMP-13浓度有类似模式。牙龈胶原酶活性的变化与牙周骨丢失的变化平行，而牙周骨丢失又反映了小梁骨密度变化。正在对作为基质金属蛋白酶抑制剂的亚抗菌剂量四环素给药的绝经后人类进行初步研究。
