Ichinose Y, Tanaka H, Inoue M, Mochizuki S, Tsuda E, Seino Y
Department of Pediatrics, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
Calcif Tissue Int. 2004 Oct;75(4):338-43. doi: 10.1007/s00223-004-0028-x. Epub 2004 Jul 30.
Skeletal unloading resulting from space flight and prolonged immobilization causes bone loss. Such bone loss ostensibly results from a rapid increase in bone resorption and subsequent sustained reduction in bone formation, but this mechanism remains unclear. Osteoclastogenesis inhibitory factor/osteoprotegerin (OCIF/OPG) is a recently identified potent inhibitor of osteoclast formation. We studied effects of OPG administration on tail-suspended growing rats to explore the therapeutic potential of OPG in the treatment and prevention of bone loss during mechanical unloading, such as that which occurs during space flight. Treatment with OPG in tail suspension increased the total bone mineral content (BMC g) of the tibia and femur and the total bone mineral density (BMD g/cm2) of the tibia. Moreover, treatment with OPG prevented reduction not only of BMC and BMD, but also of bone strength occurring through femoral diaphysis. Treatment with OPG in tail-suspended rats improved BMC, BMD and bone strength to levels of normally loaded rats treated with vehicle. Treatment with OPG in normally loaded rats significantly decreased urinary excretion of deoxypyridinoline, but the effect of OPG in tail suspension was unclear. These results indicate that OPG may be useful in inhibiting bone loss-engendered mechanical unloading.
太空飞行和长期制动导致的骨骼失用会引起骨质流失。这种骨质流失表面上是由于骨吸收迅速增加以及随后骨形成持续减少所致，但这种机制仍不清楚。破骨细胞生成抑制因子/骨保护素（OCIF/OPG）是最近发现的一种有效的破骨细胞形成抑制剂。我们研究了给予OPG对尾部悬吊的生长中大鼠的影响，以探索OPG在治疗和预防机械性失用期间骨质流失（如太空飞行期间发生的骨质流失）方面的治疗潜力。在尾部悬吊模型中用OPG治疗可增加胫骨和股骨的总骨矿物质含量（BMC，克）以及胫骨的总骨矿物质密度（BMD，克/平方厘米）。此外，用OPG治疗不仅可防止BMC和BMD的降低，还可防止股骨骨干出现的骨强度降低。在尾部悬吊的大鼠中用OPG治疗可使BMC、BMD和骨强度提高到用赋形剂处理的正常负荷大鼠的水平。在正常负荷的大鼠中用OPG治疗可显著降低脱氧吡啶啉的尿排泄，但OPG在尾部悬吊模型中的作用尚不清楚。这些结果表明，OPG可能有助于抑制机械性失用引起的骨质流失。
