PTH analogs for renal osteodystrophy and related uses
The invention relates to a mammalian cell lacking type-1 parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor (PTH1R) activity and containing carboxyl-terminal parathyroid hormone receptor (CPTHR) activity. The invention also relates to a method of screening for agonists or antagonists for CPTHR.
1. An isolated osteocyte lacking type-1 parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor (PTH1R) activity and containing carboxyl-terminal parathyroid hormone receptor (CPTHR) activity.
2. The cell of claim 1 , wherein said osteocyte is homozygous for the ablation of the PTH1R gene.
3. A method of screening for agonists or antagonists for carboxyl-terminal parathyroid hormone receptor (CPTHR), said method comprising:
(a) contacting an isolated osteocyte lacking type-1 parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP) receptor (PTH1R) activity and containing CPTHR activity with a candidate compound; and
(b) determining the rate of apoptosis of said cell,
wherein an accelerated rate of apoptosis compared to said osteocyte not contacted with a candidate compound indicates that said compound is an agonist for CPTHR, and wherein a rate of apoptosis equal to or less than said osteocyte not contacted with a candidate compound indicates that said compound is an antagonist for CPTHR.
4. The method of claim 3 , wherein said osteocyte is homozygous for the ablation of the PTH1R gene.