Conflicts of interest: The authors declare that they have no conflict of interest.
Regulation of selective PPARγ modulators in the differentiation of osteoclasts
Article first published online: 18 JUL 2013
Copyright © 2013 Wiley Periodicals, Inc.
Journal of Cellular Biochemistry
Volume 114, Issue 9, pages 1969–1977, September 2013
How to Cite
Wu, H., Li, L., Ma, Y., Chen, Y., Zhao, J., Lu, Y. and Shen, P. (2013), Regulation of selective PPARγ modulators in the differentiation of osteoclasts. J. Cell. Biochem., 114: 1969–1977. doi: 10.1002/jcb.24534
- Issue published online: 18 JUL 2013
- Article first published online: 18 JUL 2013
- Accepted manuscript online: 13 MAR 2013 09:13AM EST
- Manuscript Accepted: 28 FEB 2013
- Manuscript Received: 16 JUL 2012
- National Natural Science Foundation of China. Grant Numbers: 91013015,, 81273527,, 81121062
Diabetes is the most common chronic disease in the world and causes complications with many diseases, such as heart disease and osteoporosis. Osteoporosis is a systemic bone disease characterized by imbalance in bone resorption and bone formation. Osteoclast is type of bone cell that functions in bone resorption and plays a critical role in bone remodeling. Rosiglitazone and pioglitazone, which belong to Thiazolidinediones(TZDs), are commonly used antidiabetic drugs. As PPARγ full agonists, they can activate PPARγ in a ligand-dependent way. Recent studies indicate that these PPARγ full agonists have some side effects, such as weight gain and bone loss, which may increase the risk of osteoporosis. In contrast, selective PPARγ Modulators (SPPARγMs) are novel PPARγ ligands that can activate PPARγ in different ways and lead to distinct downstream genes. Mice bone marrow cells were stimulated with recombinant mouse RANKL and M-CSF to generate osteoclasts. To determine the effect on osteoclasts formation, PPARγ ligands (Rosiglitazone, Fmoc-L-Leu, and Telmisartan) were added at the beginning of the culture. Rosiglitazone significantly increased the differentiation of multinucleated osteoclasts, while osteoclasts formation triggered by SPPARγMs was much less than that displayed by rosiglitazone. We found that the enhancement of PPARγ ligands may be associated with TRAF6 and downstream ERK signal pathway. We also demonstrated osteoclasts show characteristic M2 phenotype and can be further promoted by PPARγ ligands, especially rosiglitazone. In conclusion, reduced osteoclasts differentiation characteristic of SPPARγMs highlights SPPARγMs potential as therapeutic targets in diabetes, versus traditional antidiabetic drugs. J. Cell. Biochem. 114: 1969–1977, 2013. © 2013 Wiley Periodicals, Inc.