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Mol. Cells 2012; 33(2): 173-181

Published online February 29, 2012

https://doi.org/10.1007/s10059-012-2240-2

© The Korean Society for Molecular and Cellular Biology

The Effects of Rosiglitazone on Osteoblastic Differentiation, Osteoclast Formation and Bone Resorption

Eui-Sic Cho1,5, Myoung-Kyun Kim1,5, Young-Ok Son2, Keun-Soo Lee3, Seung-Moon Park4, and Jeong-Chae Lee1,2,*

1Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences (Brain Korea 21 program) and School of Dentistry, Chonbuk National University, Jeonju 561-756, Korea, 2Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536-0001, USA, 3Research Laboratory, Korea Bone Bank Co. Ltd., Seoul 153-782, Korea, 4Division of Biotechnology, Chonbuk National University, Iksan 570-752, Korea, 5These authors contributed equally to this work.

Correspondence to : *Correspondence: leejc88@jbnu.ac.kr

Received: October 28, 2011; Revised: December 4, 2011; Accepted: December 5, 2011

Abstract

Rosiglitazone has the potential to activate peroxisome proliferator-activated receptor-? (PPAR?), which in turn can affect bone formation and resorption. However, the mecha-nisms by which rosiglitazone regulates osteoclastic or osteoblastic differentiation are not fully understood. This study examines how rosiglitazone affects osteoclast for-mation, bone resorption and osteoblast differentiation from mouse bone marrow. Rosiglitazone treatment not only inhibited the formation of tartrate-resistant acid phosphatase-positive cells, but also prevented pit forma-tion by bone marrow cells in a dose- and time-dependent manner. Rosiglitazone also suppressed the receptor acti-vator of nuclear factor (NF)-?B ligand (RANKL) receptor (RANK) expression but increased PPAR?2 expression in the cells. In addition, rosiglitazone diminished RANKL-induced activation of NF-?B-DNA binding by blocking I?B? phosphorylation. Furthermore, it reduced collagen and osteocalcin levels to nearly zero and prevented mRNA expression of osteoblast-specific proteins including runt-related tran-scription factor-2, osteocalcin, and type I colla-gen. How-ever, mRNA levels of adipocyte-specific marker, aP2, were markedly increased in the cells co-incubated with rosigli-tazone. These results suggest that PPAR? acti-vation by rosiglitazone inhibits osteoblast differentiation with in-creased adipogenesis in bone marrow cells and also may prevent osteoclast formation and bone resorp-tion in the cells.

Keywords mouse bone marrow cells, osteoblastogenesis, osteoclastogenesis, PPAR?, rosiglitazone

Article

Research Article

Mol. Cells 2012; 33(2): 173-181

Published online February 29, 2012 https://doi.org/10.1007/s10059-012-2240-2

Copyright © The Korean Society for Molecular and Cellular Biology.

The Effects of Rosiglitazone on Osteoblastic Differentiation, Osteoclast Formation and Bone Resorption

Eui-Sic Cho1,5, Myoung-Kyun Kim1,5, Young-Ok Son2, Keun-Soo Lee3, Seung-Moon Park4, and Jeong-Chae Lee1,2,*

1Cluster for Craniofacial Development and Regeneration Research, Institute of Oral Biosciences (Brain Korea 21 program) and School of Dentistry, Chonbuk National University, Jeonju 561-756, Korea, 2Graduate Center for Toxicology, University of Kentucky, Lexington, Kentucky 40536-0001, USA, 3Research Laboratory, Korea Bone Bank Co. Ltd., Seoul 153-782, Korea, 4Division of Biotechnology, Chonbuk National University, Iksan 570-752, Korea, 5These authors contributed equally to this work.

Correspondence to:*Correspondence: leejc88@jbnu.ac.kr

Received: October 28, 2011; Revised: December 4, 2011; Accepted: December 5, 2011

Abstract

Rosiglitazone has the potential to activate peroxisome proliferator-activated receptor-? (PPAR?), which in turn can affect bone formation and resorption. However, the mecha-nisms by which rosiglitazone regulates osteoclastic or osteoblastic differentiation are not fully understood. This study examines how rosiglitazone affects osteoclast for-mation, bone resorption and osteoblast differentiation from mouse bone marrow. Rosiglitazone treatment not only inhibited the formation of tartrate-resistant acid phosphatase-positive cells, but also prevented pit forma-tion by bone marrow cells in a dose- and time-dependent manner. Rosiglitazone also suppressed the receptor acti-vator of nuclear factor (NF)-?B ligand (RANKL) receptor (RANK) expression but increased PPAR?2 expression in the cells. In addition, rosiglitazone diminished RANKL-induced activation of NF-?B-DNA binding by blocking I?B? phosphorylation. Furthermore, it reduced collagen and osteocalcin levels to nearly zero and prevented mRNA expression of osteoblast-specific proteins including runt-related tran-scription factor-2, osteocalcin, and type I colla-gen. How-ever, mRNA levels of adipocyte-specific marker, aP2, were markedly increased in the cells co-incubated with rosigli-tazone. These results suggest that PPAR? acti-vation by rosiglitazone inhibits osteoblast differentiation with in-creased adipogenesis in bone marrow cells and also may prevent osteoclast formation and bone resorp-tion in the cells.

Keywords: mouse bone marrow cells, osteoblastogenesis, osteoclastogenesis, PPAR?, rosiglitazone

Mol. Cells
Nov 30, 2022 Vol.45 No.11, pp. 763~867
COVER PICTURE
Naive (cyan) and axotomized (magenta) retinal ganglion cell axons in Xenopus tropicalis (Choi et al., pp. 846-854).

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