Large-scale purification and characterization of human parathyroid hormone-1 receptor stably expressed in HEK293S GnTI- cells.

Human parathyroid hormone-1 receptor (hPTHR1) belongs to class II of the G protein-coupled receptor (GPCR) family, whose members all contain a seven-transmembrane helix domain. The receptor regulates bone metabolism through interactions with its ligand, human parathyroid hormone (hPTH). For structural studies of the hPTHR1/hPTH complex, we constructed a mammalian cell line to stably express recombinant hPTHR1 in large-scale.

Backbone dynamics of human parathyroid hormone (1-34): flexibility of the central region under different environmental conditions.

The presence of a stable tertiary structure in the bioactive N-terminal portion of parathyroid hormone (PTH), a major hormone in the maintenance of extracellular calcium homeostasis, is still debated. In this work, 15N relaxation parameters of the 33 backbone amides of human PTH(1-34) were determined in phosphate-buffered saline solution (PBS) and in the presence of dodecylphosphocholine (DPC) micelles. The relaxation parameters were analyzed using both the model-free formalism (G.

Differential transcriptional effects of PTH and estrogen during anabolic bone formation.

The aim of this study was to compare transcriptional regulation in vivo during anabolic bone formation induced by either estradiol (E2) treatment or intermittent parathyroid hormone[1-34] (PTH) therapy. We utilized an ovariectomized (OVX) mouse model of osteoporosis and transcriptional profiling to identify genes upregulated by either high-dose E2 or PTH. Five weeks post-OVX, the mice were administered either E2 and/or PTH, or vehicle for 4 weeks.

Transcriptional regulation of the human Runx2/Cbfa1 gene promoter by bone morphogenetic protein-7.

It is well established that core binding factor Runx2/Cbfa1 is required for osteoblast recruitment and differentiation from mesenchymal stem cells. Transcriptional regulation of the Runx2/Cbfa1 gene by osteogenic factors such as bone morphogenetic proteins (BMPs) plays an important role in the stimulation of bone formation by these cytokines. BMP7 (also termed OP-1) is a member of the transforming growth factor beta (TGF-beta) superfamily and induces osteoblast differentiation from mesenchymal precursor stem cells in vitro as well as bone formation in vivo.

Does simvastatin stimulate bone formation in vivo?

Background: Statins, potent compounds that inhibit cholesterol synthesis in the liver have been reported to induce bone formation, both in tissue culture and in rats and mice. To re-examine potential anabolic effects of statins on bone formation, we compared the activity of simvastatin (SVS) to the known anabolic effects of PTH in an established model of ovariectomized (OVX) Swiss-Webster mice.

Methods: Mice were ovariectomized at 12 weeks of age (T0), remained untreated for 5 weeks to allow development of osteopenia (T5), followed by treatment for 8 weeks (T13).

Identification of the principal binding site for RGD-containing ligands in the alpha(V)beta(3) integrin: a photoaffinity cross-linking study.

By superimposing data obtained by photo-cross-linking RGD-containing ligands to the human alpha(V)beta(3) integrin onto the crystal structure of the ectopic domain of this receptor (Xiong et al. (2001) Science 294, 339-345), we have identified the binding site for the RGD triad within this integrin. We synthesized three novel analogues of the 49-amino acid disintegrin, echistatin: [Bpa(21),Leu(28)]-, [Bpa(23),Leu(28)]-, and [Bpa(28)]echistatin.