Erschienen in:
14.10.2017 | Original Research
Kit
W-sh
Mutation Prevents Cancellous Bone Loss during Calcium Deprivation
verfasst von:
Sutada Lotinun, Jaijam Suwanwela, Suchit Poolthong, Roland Baron
Erschienen in:
Calcified Tissue International
|
Ausgabe 1/2018
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Abstract
Calcium is essential for normal bone growth and development. Inadequate calcium intake increases the risk of osteoporosis and fractures. Kit ligand/c-Kit signaling plays an important role in regulating bone homeostasis. Mice with c-Kit mutations are osteopenic. The present study aimed to investigate whether impairment of or reduction in c-Kit signaling affects bone turnover during calcium deprivation. Three-week-old male WBB6F1/J-Kit
W
/Kit
W-v
/J (W/W
v
) mice with c-Kit point mutation, Kit
W-sh
/HNihrJaeBsmJ (W
sh
/W
sh
) mice with an inversion mutation in the regulatory elements upstream of the c-Kit promoter region, and their wild-type controls (WT) were fed either a normal (0.6% calcium) or a low calcium diet (0.02% calcium) for 3 weeks. μCT analysis indicated that both mutants fed normal calcium diet had significantly decreased cortical thickness and cancellous bone volume compared to WT. The low calcium diet resulted in a comparable reduction in cortical bone volume and cortical thickness in the W/W
v
and W
sh
/W
sh
mice, and their corresponding controls. As expected, the low calcium diet induced cancellous bone loss in the W/W
v
mice. In contrast, W
sh
/W
sh
cancellous bone did not respond to this diet. This c-Kit mutation prevented cancellous bone loss by antagonizing the low calcium diet-induced increase in osteoblast and osteoclast numbers in the W
sh
/W
sh
mice. Gene expression profiling showed that calcium deficiency increased Osx, Ocn, Alp, type I collagen, c-Fms, M-CSF, and RANKL/OPG mRNA expression in controls; however, the W
sh
mutation suppressed these effects. Our findings indicate that although calcium restriction increased bone turnover, leading to osteopenia, the decreased c-Kit expression levels in the W
sh
/W
sh
mice prevented the low calcium diet-induced increase in cancellous bone turnover and bone loss but not the cortical bone loss.