Zheng M H, Lau T T, Prince R, Criddle A, Wysocki S, Beilharz M, Papadimitriou J M, Wood D J
Department of Orthopaedics, University of Western Australia, Nedlands.
Calcif Tissue Int. 1995 Feb;56(2):166-9. doi: 10.1007/BF00296350.
Tartrate-resistant acid phosphatase (TRACP) and carbonic anhydrase II (CA II) are key enzymes responsible for osteoclastic bone resorption. In this study, we proposed that estrogen loss in postmenopausal osteoporosis may enhance gene expression of TRACP and CA II, and subsequently increase osteoclastic bone resorption. We have, therefore, used the ovariectomized rat model of postmenopausal bone loss to investigate changes at the gene transcriptional level in osteoclastic bone-resorbing enzymes in ovariectomized (OVX) rats, sham ovariectomized (S-OVX) rats, and estrogen-treated ovariectomized (E-OVX) rats. We have demonstrated for the first time that ovariectomy in rats enhances gene expression of TRACP, and CA II. The mRNA levels in OVX were approximately three- and four-fold higher, respectively, than those in S-OVX. Enhancement was observed 1 week after ovariectomy and transcripts remain high during the experimental period of 8 weeks. Administration of 17 beta-estradiol to OVX (E-OVX) reduced gene expression of these osteoclastic bone-resorbing enzymes 18 hours after injection. It appeared that the suppression of the osteoclastic bone-resorbing enzymes by 17 beta-estradiol was most effective during the first 1-2 weeks but the degree of suppression was reduced at 8 weeks after ovariectomy. In conclusion, our results suggest that estrogen prevents bone loss by reducing the mRNA levels of osteoclastic bone-resorbing enzymes in bone tissue.
抗酒石酸酸性磷酸酶(TRACP)和碳酸酐酶II(CA II)是破骨细胞骨吸收的关键酶。在本研究中,我们提出绝经后骨质疏松症中雌激素的缺失可能会增强TRACP和CA II的基因表达,进而增加破骨细胞骨吸收。因此,我们使用绝经后骨质流失的去卵巢大鼠模型,来研究去卵巢(OVX)大鼠、假去卵巢(S-OVX)大鼠和雌激素治疗的去卵巢(E-OVX)大鼠破骨细胞骨吸收酶在基因转录水平的变化。我们首次证明大鼠去卵巢会增强TRACP和CA II的基因表达。OVX大鼠中的mRNA水平分别比S-OVX大鼠高约三倍和四倍。去卵巢1周后观察到增强,并且在8周的实验期内转录本一直保持高水平。给OVX大鼠注射17β-雌二醇(E-OVX)后18小时,这些破骨细胞骨吸收酶的基因表达降低。似乎17β-雌二醇对破骨细胞骨吸收酶的抑制在最初1-2周最为有效,但在去卵巢8周后抑制程度降低。总之,我们的结果表明雌激素通过降低骨组织中破骨细胞骨吸收酶的mRNA水平来预防骨质流失。