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Morphological and molecular cell biology studies on aging changes and reconstruction of bone tissue.

骨组织衰老变化和重建的形态学和分子细胞生物学研究。

基本信息

批准号：
08407056
负责人：
OZAWA Hidehiro
金额：
$ 18.75万
依托单位：
Niigata University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

[Studies on aging in bone tissue using new bone morphometrical methods] In order to establish the basic system for the research on aging phenomena in the jaw bone, we developed a new morphometrical method using confocal laser microscope and applied muCT on the bone morphometrical studies. From the results using the system, it is demonstrated that the bone loss occurred in mandibular condyle following estrogen deficiency and the condyle maintained the bone mass with dynamic structural alterations, due to regionally different reactivity against estrogen deficiency and the bone formative stimulus by occlusal force. [Histochemical studies on aging bones] With advancing age, the mandibular chondylar cartilage, which produced type II collagen fibers, became fibrocartilage-like tissue which produced type I collagen fibers. Hypertrophic chondrocytes in the condyle disappeared in the course of aging. Adipocytes were found prominently in the bone marrow of aged rat. From these results, it is sug … More gested that aging phenomena in bone tissue occurred through the control mechanisms in proliferation and differentiation of chondrocytes, osteoblasts and osteoclasts. [Molecular and cell biological studies on aging bones] Using the in situ hybridization method, we assessed the changing of the gene expression patterns in bone tissue with advancing age. In bones of OVX rats and PTHrP gene-knock out mice, gene expression patterns of osteonectin, ALPase, PTHrP, FGF and their receptor were suppressed in the course of aging. Gene expression patterns in bones with advancing age may change in association with the suppression of cell differentiation. [Inducing bone experiments] In order to prevent and recover the bone loss which occurred with aging, we assessed the effects of intermittent administration of PTH and implantation of BMP-2 pellets on mandibles of experimental animals. The preventive and therapeutic intermittent administrations of PTH in ovariectomized rats increased the bone formation in rat mandibular condyle without accelerating bone resorptive activity. When BMP-2 pellets were implanted into the extracted teeth cavities, proliferation of mesenchymal cells and differentiation of preosteoblasts into osteoblasts were induced and rapid bone formation occurred in the cavities. Furthermore, application of e-PTFE membrane after the implantation of BMP-2 pellets was effective to form the new bone into the designed bone shape. Less

[利用新型骨形态测量方法研究骨组织衰老] 为了建立颌骨衰老现象研究的基本体系，我们开发了一种利用共焦激光显微镜的新形态测量方法，并将muCT应用于骨形态测量研究。使用该系统的结果表明，雌激素缺乏后下颌骨髁突发生骨质流失，并且由于针对雌激素缺乏的区域不同的反应性和咬合力的骨形成刺激，髁突以动态结构改变维持骨量。 [老化骨骼的组织化学研究] 随着年龄的增长，产生II型胶原纤维的下颌软骨软骨变成产生I型胶原纤维的纤维软骨样组织。髁突中肥大的软骨细胞随着衰老而消失。在老年大鼠的骨髓中明显发现脂肪细胞。从这些结果推测，骨组织的衰老现象是通过软骨细胞、成骨细胞和破骨细胞的增殖和分化的控制机制发生的。 [骨骼衰老的分子和细胞生物学研究] 利用原位杂交方法，我们评估了骨组织中基因表达模式随年龄增长的变化。在OVX大鼠和PTHrP基因敲除小鼠的骨骼中，骨连接蛋白、ALPase、PTHrP、FGF及其受体的基因表达模式在衰老过程中受到抑制。随着年龄的增长，骨骼中的基因表达模式可能会因细胞分化的抑制而发生变化。【诱导骨实验】为了预防和恢复随衰老而发生的骨质流失，我们评估了间歇性给予PTH和植入BMP-2颗粒对实验动物下颌骨的影响。对去势大鼠进行预防性和治疗性间歇性给予 PTH 可以增加大鼠下颌骨髁突的骨形成，但不会加速骨吸收活性。当将BMP-2颗粒植入拔除的牙洞中时，诱导间充质细胞增殖和前成骨细胞分化为成骨细胞，并在空洞中发生快速骨形成。此外，植入BMP-2颗粒后应用e-PTFE膜可以有效地将新骨形成设计的骨形状。较少的