Local Factors in Bone Metabolism of Experimental Osteoporosis

人类骨质疏松症是由衰老、绝经和制动引起的。调节全身钙代谢的各种激素和调节局部骨组织骨代谢的各种局部因素影响着骨质疏松症的病理生理。本实验研究了制动联合卵巢切除对骨质疏松组织骨细胞局部因子基因表达的影响。采用Northern杂交的方法，用cDNA探针分析该基因的表达情况。骨质疏松胫骨中骨钙素基因表达水平明显升高。在骨质疏松的胫骨中，骨髓细胞中的转化生长因子-β基因表达水平升高，而在骨细胞中的表达略有增加。并进行了地塞米松给药实验。地塞米松组大鼠胫骨骨钙素mRNA水平显著降低。地塞米松对骨钙素表达的抑制作用在较高剂量下持续7天。Northern印迹分析显示，1，25(OH)_2D_3和2-β-(3-羟丙氧基)-1，25(OH)_2D_3均可引起骨钙素基因表达的增加。并在体外提高成骨样细胞(ROS17/2.8)中骨钙素的mRNA水平。综上所述，一般因素(雌激素、1，25(OH)_2D_3)对骨局部因子(骨钙素、转化生长因子-β)的转录调控有影响。

Human osteoporosis is induced by aging, menopause and immobilization. Various hormones which regulate calcium metabolism in the whole body and various local factors which regulate bone metabolism in local bony tissue affect on the pathophysiology of osteoporosis. The expression of mRNA of local factors in the bone cells of osteoporotic tissue induced by immobilization combined with ovariectomy was studied. The mRNA was analyzed by Northern blot method using cDNA probes. The osteocalcin mRNA level in the osteoporotic tibiae significantly increased. The TGF-beta mRNA level increased in bone marrow cells and slightly increased in bone cells in the osteoporotic tibiae. The experiment of administration of dexamethasone was also done. The osteocalcin mRNA level in the tibiae of the rats treated with dexamethasone significantly decreased. Suppressive effect of dexamethasone on osteocalcin expression was persistent for seven days at higher dose. Northern blot analysis showed that both 1,25(OH)_2D_3 and 2beta-(3-hydroxypropoxy)-1,25(OH)_2D_3 caused an increase in osteocalcin mRNA levels in bone. And they increased osteocalcin mRNA levels in osteoblast-like cells ( ROS17/2.8 ) in vitro. In conclusion, general factors ( estrogen, 1,25(OH)_2D_3 ) have an effect on the trascriptional regulation of local factors ( osteocalcin, TGF- beta ) in bone.