Amizuka N, Ozawa H, Sasaki T
Department of Oral Anatomy, Niigata University, Faculty of Dentistry, 5274, 2-Bancho, Gakkoucho-Dori, Niigata 951-8514, Japan.
Kaibogaku Zasshi. 2000 Oct;75(5):415-25.
Parathyroid hormone (PTH)-related peptide (PTHrP) was determined to be a factor inducing malignancy-associated hypercalcemia by activating a common receptor (PTH/PTHrP receptor) with PTH. PTHrP gene "knock out" mice showed a form of dyschondroplasia due to reduced proliferation of chondrocytes. In addition, heterogenous populations of variously-differentiated chondrocytes were present in the hypertrophic zone of the mutant epiphyseal plate. Although the homozygotes die within several hours after birth, the adult mice, heterozygous for PTHrP gene deletion, showed a delayed skeletal abnormality at 3 month old, with a reduced amount of PTHrP transcript, therefore, PTHrP appears to modulate cell proliferation and differentiation at both fetal and adult stages. The co-localization of PTHrP and its receptor in osteoblastic cells and chondrocytes suggested a paracrine/autocine mode of action manner of these molecules. Recently, fibroblast growth factor receptor 3 (FGFR3) deficient mice demonstrated skeletal defects including kyphosis, scoliosis, crooked tails and curvature and overgrowth of long bones and vertebrae, which are caused by an increase in proliferation. Therefore, it seems that PTHrP and FGFR3 serve as positive and negative regulators on the chondrocyte proliferation, respectively. In this paper, we review our recent studies on the histological abnormality of long bone seen in PTHrP gene deficient- and FGFR3 gene deficient-mice.
甲状旁腺激素（PTH）相关肽（PTHrP）被确定为一种通过与PTH激活共同受体（PTH/PTHrP受体）来诱导恶性肿瘤相关高钙血症的因子。PTHrP基因“敲除”小鼠由于软骨细胞增殖减少而出现一种软骨发育异常的形式。此外，在突变型骨骺板的肥大带中存在不同分化程度的软骨细胞异质群体。尽管纯合子在出生后数小时内死亡，但成年小鼠，即PTHrP基因缺失的杂合子，在3个月大时出现延迟性骨骼异常，PTHrP转录本数量减少，因此，PTHrP似乎在胎儿期和成年期均调节细胞增殖和分化。PTHrP及其受体在成骨细胞和软骨细胞中的共定位提示了这些分子的旁分泌/自分泌作用方式。最近，成纤维细胞生长因子受体3（FGFR3）缺陷小鼠表现出包括脊柱后凸、脊柱侧凸、尾巴弯曲以及长骨和椎骨弯曲和过度生长在内的骨骼缺陷，这些缺陷是由增殖增加引起的。因此，PTHrP和FGFR3似乎分别作为软骨细胞增殖的正调节因子和负调节因子。在本文中，我们综述了我们最近对PTHrP基因缺陷和FGFR3基因缺陷小鼠长骨组织学异常的研究。
