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 Dietary Prevention of Obesity-related Disease Research: Grand Forks, ND
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ARS Home Plains Area Grand Forks, North Dakota Grand Forks Human Nutrition Research Center Dietary Prevention of Obesity-related Disease Research Research Publications at this Location





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Title:   Author  item
                                            Cao, Jayitem
                                            OU, GUOMIN - University Of Georgiaitem
                                            DING, KEHONG - University Of Georgiaitem
                                            YANG, NIANLAN - University Of Georgiaitem
                                            KREAM, BARBARA - University Of Connecticutitem
                                            HAMRICK, MARK - University Of Georgiaitem
                                            ISALES, CARLOS - University Of Georgiaitem
                                            SHI, XING-MING - University Of Georgia
  Submitted to: Bone
                                    Publication Type: Peer Reviewed Journal
                                    Publication Acceptance Date: 1/25/2015
                                    Publication  Date: 7/15/2015
                                    Publication URL: https://handle.nal.usda.gov/10113/61178Citation: Cao, J.J., Ou, G., Ding, K., Yang, N., Kream, B.E., Hamrick, M.W., Isales, C.M., Shi, X. 2015. Impact of targeted PPAR gamma disruption on bone remodeling. Bone. 410:27-34.Interpretive Summary: Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand-activated nuclear receptor and is required for adipocyte differentiation. Since bone marrow mesenchymal stem cell is a common precursor for bone-forming osteoblasts and marrow adipocytes, PPAR gamma may play an important role in bone metabolism. Using a bone-specific PPAR gamma conditional knockout approach, we demonstrated that PPAR gamma deficiency abolished adipogenesis and increased osteoblastogenesis in primary bone marrow mesenchymal stem cells. Mice lacking bone-specific PPAR gamma had increased osteoblast number and surface as well as bone mass. Considering bone mass decreases and marrow fat increases with advancing age, our results suggest that PPAR gamma may play an important role in aging-related bone loss and bone-specific PPAR gamma may be a potential target for treating osteoporosis.
                                Technical Abstract: Peroxisome proliferator-activated receptor gamma (PPAR gamma), 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 PPAR gamma regulation of bone is not clear as a bone-specific PPAR gamma conditional knockout (cKO) study has not been conducted and evidence showed that deletion of PPAR''in other tissues also have profound effect on bone.  In this study, we show that mice deficiency of PPAR gamma in cells expressing a 3.6kb type I collagen promoter fragment (PPARfl/fl:Col3.6-Cre) exhibit 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 PPAR gamma cKO mice. Histology and histomorphometry studies revealed significant increases in the numbers of osteoblasts and surface in the PPAR gamma cKO mice. Finally, we found that neither the differentiation nor the function of osteoclasts was affected in the PPAR gamma cKO mice. Together, our studies indicate that PPAR gamma plays an important role in bone remodeling by increasing the abundance of osteoblasts for repair, but not during skeletal development.


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