Yamazaki Hiroko, Sasaki Takahisa
Department of Oral Histology, School of Dentistry, Showa University, Shinagawa-ku, Tokyo, Japan.
J Electron Microsc (Tokyo). 2005 Oct;54(5):467-77. doi: 10.1093/jmicro/dfi066. Epub 2005 Dec 9.
Osteoprotegerin (OPG)-deficient mice exhibit severe bone loss including the destruction of growth plate cartilage. Using OPG-deficient mice, we attempted to clarify the differentiation and ultrastructure of osteoclasts located on the destroyed growth plate cartilage and trabecular bone matrix in long bones. In (-/-) homozygous OPG knockout mice, adjacent to the growth plate cartilage, the formation of bone trabeculae without a calcified cartilaginous core resulted in an irregular chondrocyte distribution in the growth plate cartilage. At the metaphyseal ossification center, TRAP-positive osteoclasts showed unusual localization on both type-II collagen-positive cartilage and type-I collagen-positive bone matrix. Osteoclasts located on cartilage matrix lacked a typical ruffled border structure, but formed resorption lacunae. During growth plate cartilage destruction, osteoclasts formed ruffled border structures on bone matrix deposited on the remaining cartilage surfaces. These findings suggest that, in OPG (-/-) mice, osteoclast structure differs, depending on the matrix of either cartilage or bone. Then, we examined the effects of OPG administration on the internal trabecular bone structure and osteoclast differentiation in OPG (-/-) mice. OPG administration to OPG (-/-) mice significantly inhibited trabecular bone loss and maintained the internal trabecular bone structure, but did not reduce the osteoclast number on bone trabeculae. For most osteoclasts, OPG administration caused disappearance or reduction of the ruffled border, but induced neither necrotic nor apoptotic damages. These results suggest that OPG administration is an effective means of maintaining the internal structure and volume of trabecular bone in metabolic bone diseases by inhibition of osteoclastic bone resorption.
骨保护素（OPG）基因敲除小鼠表现出严重的骨质流失，包括生长板软骨的破坏。利用OPG基因敲除小鼠，我们试图阐明位于长骨中被破坏的生长板软骨和小梁骨基质上的破骨细胞的分化和超微结构。在（-/-）纯合OPG基因敲除小鼠中，在生长板软骨附近，没有钙化软骨核心的骨小梁形成导致生长板软骨中软骨细胞分布不规则。在干骺端骨化中心，抗酒石酸酸性磷酸酶（TRAP）阳性破骨细胞在II型胶原阳性软骨和I型胶原阳性骨基质上均表现出异常定位。位于软骨基质上的破骨细胞缺乏典型的皱褶缘结构，但形成了吸收陷窝。在生长板软骨破坏过程中，破骨细胞在沉积于剩余软骨表面的骨基质上形成皱褶缘结构。这些发现表明，在OPG（-/-）小鼠中，破骨细胞结构因软骨或骨基质的不同而有所差异。然后，我们研究了给予OPG对OPG（-/-）小鼠内部小梁骨结构和破骨细胞分化的影响。给OPG（-/-）小鼠注射OPG可显著抑制小梁骨丢失并维持内部小梁骨结构，但并未减少骨小梁上的破骨细胞数量。对于大多数破骨细胞，给予OPG导致皱褶缘消失或减少，但未诱导坏死或凋亡损伤。这些结果表明，通过抑制破骨细胞骨吸收，给予OPG是维持代谢性骨病中小梁骨内部结构和体积的有效手段。
