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

[用新的骨形态计量学方法研究骨组织的衰老]为了建立研究颌骨衰老现象的基本体系，我们发展了一种新的共聚焦激光显微镜形态计量学方法，并将其应用于骨形态计量学研究。结果表明，雌激素缺乏后，下颌骨发生骨丢失，由于对雌激素缺乏和咬合力的骨形成刺激的局部反应不同，下颌骨的骨量维持在动态的结构变化中。[老年骨的组织化学研究]随着年龄的增长，产生II型胶原纤维的下颌软骨成纤维软骨样组织，产生I型胶原纤维。随着年龄的增长，髁突内肥大的软骨细胞消失。老年大鼠骨髓内脂肪细胞明显增多。从这些结果来看，它是sug…更多的证据表明，骨组织中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。[衰老骨骼的分子和细胞生物学研究]利用原位杂交方法，我们研究了骨组织中基因表达谱随增龄的变化。在OVX大鼠和PTHrP基因敲除小鼠的骨骼中，随着年龄的增长，骨连接蛋白、ALPase、PTHrP、成纤维细胞生长因子及其受体的基因表达模式受到抑制。随着年龄的增长，骨骼中的基因表达模式可能会随着细胞分化的抑制而改变。[诱导骨实验]为了预防和恢复随年龄增长而发生的骨丢失，我们观察了间歇性给予甲状旁腺素和植入BMP-2微丸对实验动物下颌骨的影响。去卵巢大鼠预防性和治疗性间歇给予甲状旁腺激素，可增加其下颌骨的骨形成，但不促进骨吸收。将BMP-2微丸植入牙洞内，可诱导间充质细胞增殖和成骨前细胞向成骨细胞分化，并在牙洞内快速成骨。此外，在植入BMP-2微丸后，应用e-PTFE膜可以有效地将新骨形成设计的骨形状。较少

[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