Reasearch for control system of bone morphogy adapted to ageing or environment

骨形态是通过骨细胞、成骨细胞和破骨细胞之间的平衡或周围组织（包括软骨、血管、神经和肌腱）的相互作用来维持的。然而，骨形态因年龄、环境和物种的变化而呈现多样性的机制尚不清楚。为了阐明骨形态的控制系统，我们分析了（1）钙化骨基质的形成和维持机制，（2）骨形态随年龄、环境和物种的变化。钙定位于蛋白多糖的位点，而磷通常被映射到胶原纤维。这些结构可以保存各种矿物质，并被认为抑制了局部钙磷乘积的增加，从而维持了未钙化状态。相反，钙和磷共定位在钙化结节，而蛋白多糖的大小变得更小。蛋白多糖的这种断裂后，钙和磷的共定位被认为在钙化过程中起着重要作用。关于第二个课题，骨形态根据各种因素（包括雌激素、甲状旁腺激素、骨形态发生蛋白和张应力）的代谢或合成作用而发生变化。结果表明，张应力促进了成骨细胞的分化，BMP-4在前成骨细胞和骨周细胞中的表达增加，从而促进了成骨细胞的分化。从而阐明了金鱼的齿骨和骨的特征。

Bone morphology is maintained by the balance among osteocytes, osteoblasts and osteoclasts, or interaction of surrounding tissues including cartilage, vessels, nerve, and tendon. However, the mechnisms by which bone morphology is diverse accodrding to the alteration of age, environment, and species remain unclear. In order to elucidate control system of bone morphology, we analyzed(1) formation and mantenance mechanisms of calcified bone matrix, and (2) morphological alteration of bones, accoding to aging, environment, and species.In osteoid, meshwork of proteoglycans are oberved among collagen fibrils. Calcium was localized at the sites of proteoglycans, while phosphorus was often mapped to collagen fibrils. These structures may preserve each minerals, and are thought to inhibit the increase of local calciumXpohosphorus product, leading to the maintenence of uncalcified state. In contrast, calcium and phosphorus were co-localized at the calcified nodules, while sizes of proteoglycan became smaller there. The co-localization of calcium and phosphorus following such fragmentation of proteoglycan was thought to play an important role in undergoing calcifications.Regarding the second topics, bone morphology reaseably changes according to the metabolic or anabolic actions of various factors including estrogen, parathyroid hormone, bone morphogenetic protein, and tensile stress. Espepcially, it was revealed that osteoblastic differntiation promotes accoding to the tensile stress, mediated by increase of BMP-4 expression in preosoteoblasts and periosteoal cells.In order to examine bone diversity among spepcies, teeth and surroudning bones of gold fish were evaluated by micro CT.In micro CT analysis, fragile organs can be easily investigated without any specific prepartion. Thus, characteristics of teeht and surrouning bones of gold fish were clarified.