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25 Constitutive activation of the PTHR1 in osteocytes (DMP1-caPTHR1) results in extensive intracortical bone remodeling and increased bone mass.26 Recently, we have shown that targeted ablation of this receptor in osteocytes results in impaired calcium homeostasis.27 Therefore, we hypothesized that PTHrP might induce osteocytic perilacunar remodeling by activating the PTHR1 in osteocytes. DMP-Cre/PTHR1lox/lox (PTHR1 cKO) lactating and virgin mice were examined. http://www.selleckchem.com/products/Everolimus(RAD001).html As shown in Fig. 6A, mice lacking the PTHR1 in osteocytes (DMP-Cre PPRfl/fl), did not lose as much bone as the control animals (DMP-Cre/PTHR1lox/+; PPRlox/lox; PPRlox/+) during lactation. In addition, unlike the control mice, which showed significantly enlarged lacunae during lactation, lacunar size did not increase in either trabecular or cortical bone in PTHR1 cKO mice, suggesting that the cKO mice failed to remodel their perilacunar matrix (Fig. 6B,C). Consistent with http://www.selleck.cn/products/bmn-673.html this observation, TRAP activity (Fig. 6D,E) did not increase in osteocytes from the cKO mice during lactation. As expected, the number of TRAP-positive osteocytes increased in control animals during lactation (27.4%?��?9.6%) as compared to virgins (0.7%?��?0.9%). Immunohistochemical staining demonstrated that cathepsin K was significantly increased in osteocytes during lactation compared to virgin and postlactation osteocytes (virgin: 1.33?��?0.06; lactating: 2.15?��?0.7*; postlactation: 1.67?��?0.7; p? http://www.selleckchem.com/products/PD-0332991.html as shown in Fig. 4. Simultaneous immunohistochemical staining of wild-type virgin and lactating animals, virgin and lactating PTHR1cKO, and the PTHrP-injected animals showed significant expression in the lactating wild-type animals, but no significant increases with lactating PTHR1cKO or lactating PTHrP-injected animals (Fig. 7A,B). Cathepsin K protein tended to be higher in osteocytes from animals injected with PTHrP, but this difference was not statistically different with quantification (Fig. 7B). In addition, the expression of lacZ in osteocytes from lactating cathepsin K-Cre/R26R mice was elevated compared to virgin controls (Fig. 7C). As shown in Fig. 7C (middle panel), the cathepsin K promoter was active in some osteocytes in virgin mice but many more osteocytes expressed cathepsin K-Cre with greater intensity during lactation (Fig. 7C, lower panel). Because this mouse model is a Cre-knock-in, the endogenous promoter is being used, providing further evidence of endogenous expression in osteocytes. Together with the immunolocalization staining for protein, these data clearly demonstrate that osteocytes express cathepsin K, which is elevated during lactation.