Langub M C, Monier-Faugere M C, Qi Q, Geng Z, Koszewski N J, Malluche H H
Department of Internal Medicine, University of Kentucky Medical Center, Lexington 40536-0085, USA.
J Bone Miner Res. 2001 Mar;16(3):448-56. doi: 10.1359/jbmr.2001.16.3.448.
The parathyroid hormone/parathyroid hormone-related peptide (PTH/PTHrP) receptor (denoted as PTH-1R) is a key signaling factor through which calcium-regulating hormones PTH and PTHrP exert their effects on bone. There are contradictory reports regarding the capability of osteoclasts to express PTH-1R. To address this issue in humans, bone biopsy specimen samples from 9 normal controls and 16 patients with moderate to severe secondary renal hyperparathyroid bone disease (2 degrees HPT) with elevated PTH levels were studied to determine whether osteoclasts in the bone microenvironment express PTH-1R messenger RNA (mRNA) and protein. We report that osteoclasts express the PTH-1R mRNA but the protein is detected only in patients with 2 degrees HPT. The PTH-1R mRNA and protein also were found in osteoblasts, osteocytes, and bone marrow cells. Receptor expression was higher in osteoclasts and osteoblasts 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, respectively). Approximately half of osteoclasts found in bone of patients with 2 degrees HPT have the PTH-1R protein. In patients with 2 degrees HPT, a positive relationship exists between erosion depth, a parameter of osteoclastic activity, and the percentage of osteoclasts with PTH-1R protein (r = 0.58; p < 0.05). In normal controls, an inverse relationship exists between the percentage of osteoblasts with receptor mRNA, mRNA signals/cell, and serum PTH levels (r = -0.82 and p < 0.05 and r = -0.78 and p < 0.01, respectively). The results provide the novel evidence of PTH-1R in human osteoclasts and suggest a functional role for the receptors in 2 degrees HPT.
甲状旁腺激素/甲状旁腺激素相关肽（PTH/PTHrP）受体（记为PTH-1R）是一种关键的信号因子，钙调节激素PTH和PTHrP通过它对骨骼发挥作用。关于破骨细胞表达PTH-1R的能力，存在相互矛盾的报道。为了解决人类中的这一问题，我们研究了9名正常对照者和16名甲状旁腺激素（PTH）水平升高的中度至重度继发性肾性甲状旁腺功能亢进骨病（2度HPT）患者的骨活检标本，以确定骨微环境中的破骨细胞是否表达PTH-1R信使核糖核酸（mRNA）和蛋白质。我们报告称，破骨细胞表达PTH-1R mRNA，但仅在2度HPT患者中检测到蛋白质。在成骨细胞、骨细胞和骨髓细胞中也发现了PTH-1R mRNA和蛋白质。2度HPT患者破骨细胞和成骨细胞中的受体表达高于正常对照者（分别为98.0±1.1%对65.7±14.3%和65.8±3.4%对39.1±6.2%；p<0.01）。在2度HPT患者的骨骼中发现，约一半的破骨细胞具有PTH-1R蛋白。在2度HPT患者中，破骨细胞活性参数侵蚀深度与具有PTH-1R蛋白的破骨细胞百分比之间存在正相关（r=0.58；p<0.05）。在正常对照者中，具有受体mRNA的成骨细胞百分比、mRNA信号/细胞与血清PTH水平之间存在负相关（分别为r=-0.82，p<0.05；r=-0.78，p<0.01）。这些结果为人类破骨细胞中PTH-1R提供了新的证据，并提示该受体在2度HPT中具有功能作用。
