Trabecular bone turnover and bone marrow cell development after immobilization

在1996 - 1998年的三年中，我们明确了固定后骨小梁骨转换和骨髓细胞发育以及甲状旁腺激素（PTH）对固定相关骨质流失的影响。方法：1)6周龄雄性大鼠分别行右侧坐骨神经切除术（Nx）和左侧肢体假手术（sham）。对胫骨近端干骺端进行组织形态学研究。2)评估骨髓细胞发育情况3)进行facs分析。采用RT-PCR方法检测PTH/PTHrP mRNA的表达。4)每周皮下注射4或40g /kgBW甲状旁腺素5次。结果：1)固定后14d骨小梁体积明显减小。固定后破骨细胞瞬间增多，骨形成增多。2)固定12 d后，假手术组贴壁细胞数短暂减少，恢复到与假手术组相同。添加PTH后，Nx肢体骨髓细胞形成的破骨细胞样细胞数量增加。3) mac -1阳性细胞数量在假手术肢体和Nx肢体间无明显差异。第7.4天获得的Nx肢体骨髓细胞中PTH/PTHrP mRNA升高)4)给予PTH可防止固定相关的骨质流失。这些结果表明，固定引起骨形成的短暂减少和破骨细胞的数量增加，导致明显的骨质流失。甲状旁腺激素能增加骨髓粘附细胞的数量，促进破骨细胞的终末分化。甲状旁腺素可预防与固定相关的骨质流失。PTH/PTHrP信号通路在固定肢体骨髓细胞中被促进。

During the three years from 1996 to 1998, we clarified trabecular bone turnover and bone marrow cell development after immobilization and the effects of parathyroid hormone (PTH) on immobilization-related bone loss.Methods : 1)6 week-old ddY male mice were subjected to eitherright sciatic neurectomy (Nx) or sham operation for left limbs (Sham). Histomorphometrical study was perfonned on the proximal metaphysis of tibia. 2) Bone marrow cell development was evaluated 3) FACSanalysis was done. Using RT-PCR procedure, mRNA expression of PTH/PTHrP was studied. 4) Either of 4 or4O mug/kgBW of PTH was administered subcutaneously 5 times a week.Results : 1) Trabecular bone volume significantly decreased 14days after immobilization. The number of osteoclasts transiently increased and bone formation increased after immobilization. 2) Adherent cellnumber transiently decreased andreturned to the same values of the Sham group 12 days after immobilization. The number of osteoclast-like cell formed from the bone marrow cells obtained from the Nx limbs increased under PTH addition. 3) There was no differences in the number of Mac-1positive cells between the Nx and Sham limbs. PTH/PTHrP mRNA was elevated in the bone marrow cells obtained from the Nx limbs on day 7.4)4)PTH administration prevented immobilization-related bone loss.These results demonstrated that immbilization caused transient decrease in bone formation and increase in the number of osteoclasts, leading to significant bone loss. The number of adherentmarrow cells increased and the terminal differentiation process of osteoclasts was promoted by PTH.PTH administration prevented immobilization-related bone loss. PTH/PTHrP signaling pathway was promoted in the bone marrow cells of the immobilized limbs.