Lindsay M. Coe and Jing Zhang contributed equally to this work.
Original Research Article
Article first published online: 20 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 228, Issue 4, pages 689–695, April 2013
How to Cite
Coe, L. M., Zhang, J. and McCabe, L. R. (2013), Both spontaneous Ins2+/− and streptozotocin-induced type I diabetes cause bone loss in young mice. J. Cell. Physiol., 228: 689–695. doi: 10.1002/jcp.24177
Conflict of Interest Statement: Authors have nothing to disclose.
- Issue published online: 20 DEC 2012
- Article first published online: 20 DEC 2012
- Accepted manuscript online: 9 AUG 2012 07:36AM EST
- Manuscript Accepted: 2 AUG 2012
- Manuscript Received: 26 JUL 2012
- American Diabetes Association. Grant Number: 7-07-RA-105
The adolescent skeleton undergoes accelerated growth determining overall bone density, length, and quality. Diseases such as type 1 diabetes (T1D), most often diagnosed in adolescents, can alter bone processes and promote bone loss. Studies examining type 1 diabetic (T1D) bone pathologies typically utilize adult mice and rely on pharmacologic models such as streptozotocin (STZ)-induced diabetic rodents. To test the effect of T1D on adolescent bone growth/density we used a novel juvenile genetic model (Ins2+/− mice) that spontaneously develop T1D at approximately 5 weeks of age and compared our findings with STZ-induced T1D mice. Compared to controls, both Ins2+/− and STZ-induced T1D mice displayed blood glucose levels greater than 300 mg/dl and reduced body, fat and muscle mass as well as femur trabecular bone density. STZ mice exhibited greater bone loss compared to Ins2+/− mice despite having lower blood glucose levels. Cortical bone was affected in STZ but not Ins2+/− mice. Osteocalcin serum protein and bone RNA levels decreased in both models. Consistent with studies in adult mice, STZ adolescent mice displayed increased marrow adiposity, however this was not observed in the Ins2+/− mice. Reduced femur length, decreased growth plate thickness and decreased collagen II expression in both model simplies impaired cartilage formation. In summary, both pharmacologic and spontaneous adolescent T1D mice demonstrated a bone synthesis and growth defect. STZ appears to cause a more severe phenotype. Thus, the Ins2+/− mouse could serve as a useful model to study adolescent T1D bone loss with fewer complications. J. Cell. Physiol. 228: 689–695, 2013. © 2012 Wiley Periodicals, Inc.