Effect of essential trace metal on bone metabolism in the femoral-metaphyseal tissues of rats with skeletal unloading: comparison with zinc-chelating dipeptide.
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.
Yamaguchi
M
M
Laboratory of Endocrinology and Molecular Metabolism, Graduate School of Nutritional Sciences, University of Shizuoka, 52-1 Yada, Shizuoka City 422, Japan.
Ehara
Y
Y
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002336:Carnosine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D046508:Culture Techniques; D004247:DNA / Q000378:metabolism; D018483:Diaphyses / Q000378:metabolism; D005269:Femur / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008682:Metatarsal Bones / Q000187:drug effects* / Q000378:metabolism; D009942:Organometallic Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013431:Sulfates / Q000494:pharmacology; D014131:Trace Elements / Q000494:pharmacology*; D015032:Zinc / Q000494:pharmacology*; D017967:Zinc Compounds / Q000494:pharmacology; D019287:Zinc Sulfate
D009942:Organometallic Compounds; D013431:Sulfates; D014131:Trace Elements; D017967:Zinc Compounds; C061957:polaprezinc; D019287:Zinc Sulfate; D002336:Carnosine; D004247:DNA; D000469:Alkaline Phosphatase; D015032:Zinc