Yamaguchi M, Ehara Y
Laboratory of Endocrinology and Molecular Metabolism, Graduate School of Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka City 422, Japan.
Calcif Tissue Int. 1996 Jul;59(1):27-32. doi: 10.1007/s002239900081.
The effect of essential trace metals on bone metabolism was investigated in the femoral-metaphyseal tissues obtained from skeletal-unloaded rats. Skeletal unloading was designed by using the model of hindlimb suspension in rats; the animals were fed for 4 days with the unloading. Femoral-metaphyseal tissues were cultured for 24 hours in a medium containing either vehicle (control), nickel, manganese, cobalt, copper, zinc, or zinc-chelating dipeptide (beta-alanyl-L-histidinato zinc; AHZ) in the concentration range of 10(-6) to 10(-4) M. Bone biochemical components (alkaline phosphatase activity, glucose consumption, and DNA content) were significantly decreased by skeletal unloading. The presence of zinc sulfate or AHZ (10(-5) and 10(-4) M) caused a significant increase of alkaline phosphatase activity in the bone tissues from unloaded rats. This effect was not seen by nickel, manganese, cobalt and copper (10(-6) to 10(-4) M). The culture medium glucose was clearly consumed by the bone tissues. This consumption was inhibited by nickel, manganese, or copper (10(-5) and 10(-4) M), while cobalt, zinc, and AHZ had no effect. DNA content in the bone tissues from unloaded rats was significantly increased by all metal compounds (10(-5) M). The effect of AHZ on bone components was greater than zinc sulfate. The AHZ (10(-5) M)-increased alkaline phosphatase activity in the bone tissues from unloaded rats was clearly blocked by the presence of cycloheximide (10(-6) M), staurosporine (10(-7) M), dibucaine (10(-4) M), or okadaic acid (10(-7) M). The present study demonstrates that, of various essential trace metals, zinc compounds have an unique anabolic effect on bone metabolism in the femoral-metaphyseal tissues of rats with skeletal unloading. Zinc-chelating dipeptide may stimulate bone protein synthesis through the mechanism that is involved in protein kinases.
在从骨骼去负荷大鼠获取的股骨-干骺端组织中，研究了必需微量元素对骨代谢的影响。通过使用大鼠后肢悬吊模型设计骨骼去负荷；动物在去负荷状态下喂养4天。将股骨-干骺端组织在含有载体（对照）、镍、锰、钴、铜、锌或锌螯合二肽（β-丙氨酰-L-组氨酸锌；AHZ）的培养基中培养24小时，浓度范围为10(-6)至10(-4)M。骨骼去负荷显著降低了骨生化成分（碱性磷酸酶活性、葡萄糖消耗和DNA含量）。硫酸锌或AHZ（10(-5)和10(-4)M）的存在导致去负荷大鼠骨组织中碱性磷酸酶活性显著增加。镍、锰、钴和铜（10(-6)至10(-4)M）未观察到这种作用。骨组织明显消耗培养基中的葡萄糖。这种消耗受到镍、锰或铜（10(-5)和10(-4)M）的抑制，而钴、锌和AHZ没有影响。所有金属化合物（10(-5)M）均使去负荷大鼠骨组织中的DNA含量显著增加。AHZ对骨成分的作用大于硫酸锌。AHZ（10(-5)M）增加的去负荷大鼠骨组织碱性磷酸酶活性明显被放线菌酮（10(-6)M）、星形孢菌素（10(-7)M）、丁卡因（10(-4)M）或冈田酸（10(-7)M）的存在所阻断。本研究表明，在各种必需微量元素中，锌化合物对骨骼去负荷大鼠股骨-干骺端组织的骨代谢具有独特的合成代谢作用。锌螯合二肽可能通过涉及蛋白激酶的机制刺激骨蛋白合成。
