Parathyroid hormone/parathyroid hormone-related peptide type 1 receptor inhuman bone

The parathyroid hormone/parathyroid hormone-related peptide (PTH/PTHrP) rec eptor (denoted as PTH-1R is a key signaling factor through which calcium-re gulating hormones PTH and PTHrP exert their effects on bone, There are cont radictory reports regarding the capability of osteoclasts to express PTH-1R . To address this issue in humans, bone biopsy specimen samples from 9 norm al controls and 16 patients with moderate to severe secondary renal hyperpa rathyroid bone disease (2 degrees HPT) with elevated PTH levels were studie d to determine whether osteoclasts in the bone microenvironment express PTH -1R messenger RNA (mRNA) and protein, We report that osteoclasts express th e PTH-1R mRNA but the protein is detected only in patients with 2 degrees H PT, The PTH-1R mRNA and protein also were found in osteoblasts, osteocytes, and bone marrow cells, Receptor expression was higher in osteoclasts and o steoblasts of patients with 2 degrees HPT than normal controls (98.0 +/- 1. 1% vs, 65.7 +/- 14.3% and 65.8 +/- 3.4% vs. 39.1 +/- 6.2% ; p < 0,01, respe ctively), Approximately half of osteoclasts found in bone of patients with 2<degrees>KPT have the PTH-1R protein. In patients with 2 degrees HPT, a po sitive relationship exists between erosion depth, a parameter of osteoclast ic activity, and the percentage of osteoclasts with PTH-1R protein (r = 0,5 8; p < 0,05), In normal controls, an inverse relationship exists between th e percentage of osteoblasts with receptor mRNA, mRNA signals/cell, and seru m PTH levels (r = -0.82 and p < 0.05 and r = -0.78 and p < 0.01, respective ly). The results provide the novel evidence of PTH-1R in human osteoclasts and suggest a functional role for the receptors in 2<degrees>HPT.