Caspase-2 deficiency protects mice from diabetes-induced marrow adiposity
Article first published online: 18 AUG 2011
Copyright © 2011 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 112, Issue 9, pages 2403–2411, September 2011
How to Cite
Coe, L. M., Lippner, D., Perez, G. I. and McCabe, L. R. (2011), Caspase-2 deficiency protects mice from diabetes-induced marrow adiposity. J. Cell. Biochem., 112: 2403–2411. doi: 10.1002/jcb.23163
- Issue published online: 18 AUG 2011
- Article first published online: 18 AUG 2011
- Accepted manuscript online: 2 MAY 2011 06:55AM EST
- Manuscript Accepted: 20 APR 2011
- Manuscript Received: 16 APR 2011
- NIH. Grant Number: DK061184
- American Diabetes Association. Grant Number: 7-07-RA-105
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.