Strain dependent differences in glucocorticoid-induced bone loss between C57BL/6J and CD-1 mice.
We have investigated the effect of long-term glucocorticoid (GC) administration on bone turnover in two frequently used mouse strains; C57BL/6J and CD1, in order to assess the influence of their genetic background on GC-induced osteoporosis (GIO). GIO was induced in 12 weeks old female C57BL/6J and CD1 mice by subcutaneous insertion of long-term release prednisolone or placebo pellets. Biomechanical properties as assessed by three point bent testing revealed that femoral elasticity and strength significantly decreased in CD1 mice receiving GC, whereas C57BL/6J mice showed no differences between placebo and prednisolone treatment. Bone turnover assessed by microcomputer tomography revealed that contrary to C57BL/6J mice, prednisolone treated CD1 mice developed osteoporosis. In vitro experiments have underlined that, at a cellular level, C57BL/6J mice osteoclasts and osteoblasts were less responsive to GC treatment and tolerated higher doses than CD1 cells. Whilst administration of long-term release prednisolone pellets provided a robust GIO animal model in 12 weeks old CD1 mice, age matched C57BL/6J mice were not susceptible to the bone changes associated with GIO. This study indicates that for the induction of experimental GIO, the mouse strain choice together with other factors such as age should be carefully evaluated.
The Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford, OX3 7FY, UK.
Adel
A
Ersek
The Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford, OX3 7FY, UK.
Ana I Espirito
AI
Santo
The Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford, OX3 7FY, UK.
Youridies
Y
Vattakuzhi
The Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford, OX3 7FY, UK.
Saumya
S
George
University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK.
Andrew R
AR
Clark
The Kennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford, OX3 7FY, UK.
Nicole J
NJ
Horwood
D000818:Animals; D015519:Bone Density / Q000187:drug effects* / Q000502:physiology*; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000503:physiopathology*; D005938:Glucocorticoids / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology; D010024:Osteoporosis / Q000139:chemically induced* / Q000503:physiopathology*; D011239:Prednisolone / Q000494:pharmacology
D005938:Glucocorticoids; D011239:Prednisolone