Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: 11/10/2005
Publication Date: 3/6/2006
Citation: Hadley, K.B., Hunt, J.R. 2006. Zinc regulation of skeletal matrix remodeling activities in growing rats [abstract]. FASEB J. 20(4):A626.
Technical Abstract: Zinc (Zn) deficiency causes abnormal skeletal development involving growth plate defects. Therefore, Zn regulation of bone matrix synthesis and resorption was investigated. Male weanling rats (n=6/group) were fed an AIN-96G based diet with egg albumin, containing 2.5, 5, 7.5, 15, or 30 µg/g Zn as ZnCO3 for 21d. Femur Zn and SLC39A2 (Zip2) mRNA levels were used as indicators of changes in bone Zn status. The Zn metalloenzymes, femur alkaline and tartrate resistant alkaline phosphatases (ALP and TRAP, respectively), carbonic anhydrase II (CAII), and matrix metalloproteinase (MMP) -2 and -9 activities from femoral-head extracts were measured. Femur Zn (means + SEM) increased directly (p < 0.05) from 0.9 + 0.1 to 4.2 + 0.1 µmols Zn/g dry weight in rats fed 5 to 30 µg Zn/g diet. Changes in Zip-2 gene expression were at least 10-fold greater between 5 and 15 µg Zn/g diet, and then decreased to less than 50% at 30 µg/g, relative to rats fed 2.5µg/g. Average delta threshold cycle numbers were not significantly different, however. ALP and TRAP p-nitrophenol (pNP) release activities increased (p<0.05, 22 + 9 to 61 + 11 and 6 + 1 to 16 + 1 µmols pNP/mg, respectively) with dietary Zn from 7.5 to 30 µg/g diet. In contrast, zymography of MMP-2 and -9 showed decreased activities (p < 0.05, 26 + 2 to 4 + 2 and 9 + 1 to 2 + 1 units) from 2.5 to 5 µg Zn/g diet and then remained level, relative to 30 µg Zn/g values. CAII activity also remained nearly constant from 2.5 to 15 µg Zn/g, and then decreased from 21+ 2 to 13 + 3 munits/mg (p < 0.05) at 30 µg Zn/g diet. These results indicate a dietary Zn requirement greater than 15µg/g for optimal bone mineralization potential in growing rats, and provide insight into osseous Zip-2 regulation by Zn status.