J Korean Soc Osteoporos.  2010 Apr;8(1):47-55.

Differential Expression of RANKL and OPG by the PPAR gamma Agonist Rosiglitazone in Osteoblasts

• Lee MJ
• Lee SY
• Park SH
• Ahn DW

Abstract

OBJECTIVES
Osteoblasts secrete receptor activator of nuclear factor-kB ligand (RANKL) and osteoprotegerin (OPG). RANKL stimulates osteoclastogenesis but OPG inhibits it by binding with RANKL. Although peroxisome proliferation-activated receptor gamma (PPARgamma) has a major role in adipocyte differentiation, it is also involved in bone remodeling. The aim of this study was to examine whether rosiglitazone, the PPARgamma agonist, regulates the expression of RANKL and OPG in osteoblasts.
METHODS
MC3T3-E1 osteoblasts were cultured and treated with different concentrations of rosiglitazone. Cell viability was assayed with MTT. A conventional PCR was used for the detection of PPARgamma gene. Expression of RANKL and OPG mRNA and their protein levels was analyzed by quantitative real-time RT-PCR and Western blot, respectively.
RESULTS
PPARgamma mRNA was expressed in MC3T3-E1 osteoblasts and its expression was greatly increased by treatment of 5microM rosiglitazone. Treatment with 1 to 10microM rosiglitazone did not affect cell viability. Compared with vehicle, rosiglitazone (5microM) up-regulated OPG mRNA expression by 2.3-fold and down-regulated RANKL mRNA expression by 5-fold, which was reversed by the PPARgamma antagonist GW9662. The level of RANKL and OPG protein varied as compared to their mRNA expression.
CONCLUSION
These results demonstrate that activation of PPARgamma by rosiglitazone induces both down-regulation of RANKL and up-regulation of OPG in osteoblasts, which is likely to cause an inhibition of osteoclastogenesis.

Keyword

OPG; Osteoblast; RANKL; Rosiglitazone

MeSH Terms

Adipocytes
Anilides
Blotting, Western
Bone Remodeling
Cell Survival
Down-Regulation
Osteoblasts
Osteoprotegerin
Peroxisome Proliferator-Activated Receptors
Peroxisomes
Polymerase Chain Reaction
PPAR gamma
RNA, Messenger
Thiazolidinediones
Up-Regulation
Anilides
Osteoprotegerin
PPAR gamma
Peroxisome Proliferator-Activated Receptors
RNA, Messenger
Thiazolidinediones