title: Impact of targeted PPARγ disruption on bone remodeling.
abstract: Peroxisome proliferator-activated receptor gamma (PPARγ), known as the master regulator of adipogenesis, has been regarded as a promising target for new anti-osteoporosis therapy due to its role in regulating bone marrow mesenchymal stem/progenitor cell (BMSC) lineage commitment. However, the precise mechanism underlying PPARγ regulation of bone is not clear as a bone-specific PPARγ conditional knockout (cKO) study has not been conducted and evidence showed that deletion of PPARγ in other tissues also have profound effect on bone. In this study, we show that mice deficiency of PPARγ in cells expressing a 3.6 kb type I collagen promoter fragment (PPAR(fl/fl):Col3.6-Cre) exhibits a moderate, site-dependent bone mass phenotype. In vitro studies showed that adipogenesis is abolished completely and osteoblastogenesis increased significantly in both primary bone marrow culture and the BMSCs isolated from PPARγ cKO mice. Histology and histomorphometry studies revealed significant increases in the numbers of osteoblasts and surface in the PPARγ cKO mice. Finally, we found that neither the differentiation nor the function of osteoclasts was affected in the PPARγ cKO mice. Together, our studies indicate that PPARγ plays an important role in bone remodeling by increasing the abundance of osteoblasts for repair, but not during skeletal development.
authors: USDA ARS Grand Forks Human Nutrition Research Center, Grand Forks, ND, United States.
authors: Jay
authors: J
authors: Cao
authors: Department of Neuroscience & Regenerative Medicine, Georgia Regents University, Augusta, GA, United States.
authors: Guomin
authors: G
authors: Ou
authors: Department of Neuroscience & Regenerative Medicine, Georgia Regents University, Augusta, GA, United States.
authors: Nianlan
authors: N
authors: Yang
authors: Department of Neuroscience & Regenerative Medicine, Georgia Regents University, Augusta, GA, United States.
authors: Kehong
authors: K
authors: Ding
authors: Department of Medicine, University of Connecticut Health Center, Farmington, CT, United States.
authors: Barbara E
authors: BE
authors: Kream
authors: Department of Cell Biology, Georgia Regents University, Augusta, GA, United States.
authors: Mark W
authors: MW
authors: Hamrick
authors: Department of Neuroscience & Regenerative Medicine, Georgia Regents University, Augusta, GA, United States; Department of Orthopaedic Surgery, Georgia Regents University, Augusta, GA, United States.
authors: Carlos M
authors: CM
authors: Isales
authors: Department of Neuroscience & Regenerative Medicine, Georgia Regents University, Augusta, GA, United States; Department of Orthopaedic Surgery, Georgia Regents University, Augusta, GA, United States. Electronic address: xshi@gru.edu.
authors: Xing-Ming
authors: XM
authors: Shi
mesh_terms: D050156:Adipogenesis; D000818:Animals; D016723:Bone Remodeling; D002454:Cell Differentiation; D002478:Cells, Cultured; D055786:Gene Knockout Techniques; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D010006:Osteoblasts / Q000502:physiology; D010010:Osteoclasts / Q000502:physiology; D010012:Osteogenesis; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic
chemical_list: D047495:PPAR gamma
keywords: Aging; Bone loss; MSC; Osteoblasts; PPARγ