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Values were considered statistically significant at p? http://www.selleckchem.com/products/ch5424802.html revealed that the trabecular morphology in the AT1a knockout mice was characterized by an increased number and connectivity and decreased separation (Fig. 1B). The heterozygous mice exhibited an intermediate phenotype in terms of both bone mass and trabecular microstructure. The high bone mass phenotype of the AT1a-deficient mice was also found in the female mice (Fig. 1C, D). There was no significant difference in the cortical bone area or volume between AT1a knockout and wild-type mice, as determined by micro CT scanning of tibial diaphysis (data not shown). We examined the effects of aging and estrogen deficiency on the high bone mass phenotype of AT1a-deficient mice. As shown in Figure 2A, 25-month-old male AT1a knockout mice maintained higher bone mass than age- and sex-matched wild-type mice. Also, as shown in Figure 2B, AT1a-deficient female mice were protected against ovariectomy-induced bone loss. Biochemical analysis of blood samples indicated that the serum concentrations http://www.selleck.cn/products/Everolimus(RAD001).html of osteocalcin, a product of osteoblasts, and CTX, a degradation product of type I collagen, were both significantly higher in AT1a-deficient mice than in age- and sex-matched wild-type mice (Fig. 3), which indicates a state of high bone turnover. Serum and urinary calcium and plasma PTH levels did not differ among the three genotypes (Fig. 3), which makes it unlikely that the high bone mass and high bone turnover found in AT1a knockout mice are secondary to alterations in systemic calcium metabolism. The mechanism underlying the high bone mass of the AT1a knockout mice was further explored at the tissue and cell levels by histomorphometric analysis of the proximal http://www.selleckchem.com/products/azd9291.html tibia, which revealed that the number of osteoclast (N.Oc/BS), the bone surface area covered by osteoclasts (Oc.S/BS), and the eroded surface (ES/BS) were all significantly elevated in the homozygous knockout mice (Fig. 4), indicating that the osteoclast number and bone resorption activity are increased in the absence of AT1a. The osteoid surface (OS/BS), osteoblast surface (Ob.S/BS), and bone formation rate (BFR/BS) were significantly increased in the AT1a-deficient mice (Fig. 4), indicating that bone formation was also stimulated along with accelerated bone resorption.