Page 5 of 7
Journal Name
MedChemComm
DOI: 10.1039/C5MD00215J
The effect of RGDꢀtetrapeptide covalent modification on
osteoporotic risk was further estimated with the femur weight
of BALB/C mice (male, 14 weeks in age) orally receiving 0.5
% CMCꢀNa or 1.43 ꢁmol/kg/day of Dex or the conjugates for
15 consecutive days. Figure 6 indicates that the dry femur
weight and the ash weight of the mice receiving 0.5 % CMCꢀ
Na, and 1.43 ꢁmol/kg/day of RGDVꢀDex or RGDSꢀDex or
RGDFꢀDex have the close values, suggesting during 15ꢀday
treatments they induce no femur loss, while the dry femur
weight and the ash weight of the mice receiving 1.43
ꢁmol/kg/day of Dex are lower than that of the mice receiving
0.5 % CMCꢀNa, suggesting during 15ꢀday treatments Dex
induces femur loss (Figure 6a,b). The phenomena is also
found in femur calcium, but not femur phosphor (Figure
6c,d). All data emphasize that RGDꢀ tetrapeptide covalent
modification effectively decreases the osteoporotic risk of Dex
therapy.
81273379, 81373265, 81202412, 81373264), Beijing Natural
Science Foundation (7132032), 863 program (2015AA020902)
and KZ201210025021.
Notes and references
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Figure 6 (a) Femur weight, (b) femur ash weight, (c) femur calcium and
(d) femur phosphor of the mice orally treated with 0.5 % CMCꢀNa, 1.43
ꢁmol/kg/day of Dex, 1.43 ꢁmol/kg/day of RGDVꢀDex, 1.43 ꢁmol/kg/day
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Experimental
The detailed methodologies and data of all experiments are
given as Supporting Information.
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The covalent modification of Dex with RGDV, RGDS and
RGDF can effectively increase the antiꢀinflammatory activity
and lower the osteoporotic risk of Dex therepy, and therefore
is a general strategy to improve the clinical antiꢀinflammatory
therapy of glucocorticoids. The enhancement of the antiꢀ
inflammatory activity may attribute to the abilities of RGDVꢀ
Dex, RGDSꢀDex and RGDFꢀDex to cross membrane and
downꢀregulate DNA replication. To clarify the responsible
integrin for RGDVꢀDex, RGDSꢀDex and RGDFꢀDex to have
higher antiꢀinflammatory activity and lower side reaction is of
pharmacological importance, is one of our interests and should
be deeply investigated.
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Acknowledgements
This work was supported by Beijing Municipal Science &
Technology Commission (Z141100002114049), the Project of
Construction of Innovative Teams and Teacher Career
Development for Universities and Colleges Under Beijing
Municipality, TJSHG (201310025008), the NSFC (81172930,
This journal is © The Royal Society of Chemistry 2013
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