Mechanism of calcification of hard tissue suggested by special calcification preceding to bone induction

在本研究中，我们发现脱钙骨基质明胶(BMG)中的球形矿物质沉积先于骨形态发生蛋白(BMP)诱导的真正骨形成，并因其形成不依赖于成骨细胞而被称为“脱细胞矿物质沉积”(AMD)。为探讨AMD的发病机制及其与硬组织形成的关系，分别植入热变性BMG、热变性脱矿牙胚(DTG)或戊二醛交联的小牛皮胶原，观察植入后第1、3、5、7、10天的组织学变化。结果表明，在第3天，无论是在热变性…的骨基质中还是在牙本质基质中，热变性DTG的牙本质基质中都没有出现类似于牙本质的球形矿化结构，而在交联型胶原中，出现了类似于骨的继发性钙化的钙化。植入后上述钙化均独立于任何正常形成细胞和基质小泡的硬组织内。这些结果表明，骨中的钙化和牙本质的形成可能发生在物理化学上。因此，我们提出了一种硬组织形成的“基质转化理论”：该理论的主要观点如下：(1)硬组织形成细胞首先形成未成熟的基质。(2)将未成熟的基质改变为各种可钙化基质中的任何一种。(3)钙化发生在可钙化的基质中。在OP/OP小鼠上，组织学和结构研究发现，软骨内骨化比膜内骨化受到更强的抑制。尤其是软骨细胞向成骨细胞转化，成骨细胞分化受到严重抑制。软骨基质内可见特殊钙化。现在，为了阐明这些观点，我们进行了超微结构和组织化学研究。较少

In the present study, we found that an appearance of spherical mineral deposits in demineralized bone matrix gelatin (BMG) preceded the true bone formation induced by bone morphogenetic protein (BMP) and named that "acellular mineral deposition" (AMD) because of their formation independent of osteogenic cells. Still more, in order to elucidate the mechanism of AMD and its relation to hard tissue formation, heat-denatured BMG,heat-denatured demineralized tooth germ (DTG), or calf skin collagen cross-linked with glutaraldehyde was implanted, and then histological changes in the implants were observed on day 1,3,5,7 and 10 after implantation. The results showed that spherical mineralized structures, which resembled globular dentine, appeared first on day 3 both in the bone matrix of heat-denatured BMG and in the dentine matrix, but not in the pre-dentine matrix, of heat-denatured DTG.In cross-linked collagen, however, a calcification which resembled secondary calcification of bone appeare … More d first on day 3. The above post implantation calcifications all occurred independently in any hard tissue normally forming cells and matrix vesicles. These results suggests that calcification in bone and dentine formation may occur physicochemically. Thus, we propose a "Matrix Transforming Theory" for hard tissue formation : The main points of this theory are as follows. (1) Hard tissue forming cells first form the immature matrix. (2) The immature matrix is changed to any of the various calcifiable matrices. (3) The calcification physicochemically occurs in the calcifiable matrix. On the op/op mouse, It was found that endochondral ossication was suppresed stronger than intramembranous ossification, from the histological and structural study. Especially, transform from chondrocyte to osteoblaste and differentiation of osteoblasts was severly inhibited. Still more, special calcification on cartilagenous matrix was found. Now, in order to elucidate these points, we ultrastructurally and histochemically study. Less