Caspase-2 deficiency protects mice from diabetes-induced marrow adiposity
Type I (T1) diabetes is an autoimmune and metabolic disease associated with bone loss. Bone formation and density are decreased in T1‐diabetic mice. Correspondingly, the number of TUNEL positive, dying osteoblasts increases in bones of T1‐diabetic mice. Moreover, two known mediators of osteoblast de...
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Published in | Journal of cellular biochemistry Vol. 112; no. 9; pp. 2403 - 2411 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.09.2011
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Subjects | |
Online Access | Get full text |
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Summary: | Type I (T1) diabetes is an autoimmune and metabolic disease associated with bone loss. Bone formation and density are decreased in T1‐diabetic mice. Correspondingly, the number of TUNEL positive, dying osteoblasts increases in bones of T1‐diabetic mice. Moreover, two known mediators of osteoblast death, TNFα and ROS, are increased in T1‐diabetic bone. TNFα and oxidative stress are known to activate caspase‐2, a factor involved in the extrinsic apoptotic pathway. Therefore, we investigated the requirement of caspase‐2 for diabetes‐induced osteoblast death and bone loss. Diabetes was induced in 16‐week old C57BL/6 caspase‐2 deficient mice and their wild type littermates and markers of osteoblast death, bone formation and resorption, and marrow adiposity were examined. Despite its involvement in extrinsic cell death, deficiency of caspase‐2 did not prevent or reduce diabetes‐induced osteoblast death as evidenced by a twofold increase in TUNEL positive osteoblasts in both mouse genotypes. Similarly, deficiency of caspase‐2 did not prevent T1‐diabetes induced bone loss in trabecular bone (BV/TV decreased by 30 and 50%, respectively) and cortical bone (decreased cortical thickness and area with increased marrow area). Interestingly, at this age, differences in bone parameters were not seen between genotypes. However, caspase‐2 deficiency attenuated diabetes‐induced bone marrow adiposity and adipocyte gene expression. Taken together, our data suggest that caspase‐2 deficiency may play a role in promoting marrow adiposity under stress or disease conditions, but it is not required for T1‐diabetes induced bone loss. J. Cell. Biochem. 112: 2403–2411, 2011. © 2011 Wiley‐Liss, Inc. |
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Bibliography: | NIH - No. DK061184 istex:13D04A5E766FE4097BF93AD4EED836EA73F2954B American Diabetes Association - No. 7-07-RA-105 ark:/67375/WNG-B0Q90W7F-7 ArticleID:JCB23163 ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0730-2312 1097-4644 |
DOI: | 10.1002/jcb.23163 |