Changes in Osteoblast, Chondrocyte, and Adipocyte Lineages Mediate the Bone Anabolic Actions of PTH and Small Molecule GSK-3 Inhibitor.

Changes in Osteoblast, Chondrocyte, and Adipocyte Lineages Mediate the Bone Anabolic Actions of PTH and Small Molecule GSK-3 Inhibitor. Research Abstract Details 

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Changes in Osteoblast, Chondrocyte, and Adipocyte Lineages Mediate the Bone Anabolic Actions of PTH and Small Molecule GSK-3 Inhibitor. Abstract Text:

Nalini H Kulkarni,Tao Wei,Amar Kumar,Ernst R Dow,Trent R Stewart,Jianyong Shou,Mathias N'cho,Diane L Sterchi,Bruce D Gitter,Richard E Higgs,David L Halladay,Thomas A Engler,T John Martin,Henry U Bryant,Yanfei L Ma,Jude E Onyia,Nalini H Kulkarni,Tao Wei,Amar Kumar,Ernst R Dow,Trent R Stewart,Jianyong Shou,Mathias N'cho,Diane L Sterchi,Bruce D Gitter,Richard E Higgs,David L Halladay,Thomas A Engler,T John Martin,Henry U Bryant,Yanfei L Ma,Jude E Onyia,

Parathyroid hormone (PTH) and glycogen synthase kinase-3 (GSK-3) inhibitor 603281-31-8, administered once daily increased bone formation in vivo. We investigated the molecular mechanisms of the anabolic responses of PTH and 603281-31-8 in rat osteopenia model. Female 6-month-old rats were ovariectomized (Ovx) and permitted to lose bone for 1 month, followed by treatment with PTH (1-38) at 10 microg/kg/day s.c. or 603281-31-8 at 3 mg/kg/day p.o. for 60 days. Twenty-four hours after the last treatment, RNA from distal femur metaphysis was subjected to gene expression analysis. Differentially expressed genes (P < 0.05) were subjected to pathway analysis to delineate relevant bio-processes involved in skeletal biology. Genes involved in morphogenesis, cell growth/differentiation, and apoptosis were significantly altered by Ovx and the treatments. Analysis of morphogenesis genes showed an overrepresentation of genes involved in osteogenesis, chondrogenesis, and adipogenesis. A striking finding was that Ovx decreased several markers of osteogenesis/chondrogenesis and increased markers of adipogenesis/lipid metabolism. Treatment with either PTH or the GSK-3 inhibitor reversed these effects, albeit at different levels. Histological analysis confirmed that osteopenia in Ovx animals was associated with three-fold increase in marrow adiposity. PTH and GSK-3 inhibitor restored bone volume, and reversed or normalized marrow adiposity. Ex vivo studies showed that PTH and GSK-3 inhibitor increased the ratio of colony forming marrow stromal progenitors (CFU-fs) that were alkaline phosphatase positive (putative osteoblasts). Our results suggest that the bone anabolic actions of PTH and GSK-3 inhibitor in vivo involve concerted effects on mesenchymal lineages; osteoblasts, chondrocytes, and adipocytes. J. Cell. Biochem. 102: 1504-1518, 2007. (c) 2007 Wiley-Liss, Inc.

Changes in Osteoblast, Chondrocyte, and Adipocyte Lineages Mediate the Bone Anabolic Actions of PTH and Small Molecule GSK-3 Inhibitor. Publishing Authors By Initials

NH Kulkarni,T Wei,A Kumar,ER Dow,TR Stewart,J Shou,M N'cho,DL Sterchi,BD Gitter,RE Higgs,DL Halladay,TA Engler,TJ Martin,HU Bryant,YL Ma,JE Onyia,NH Kulkarni,T Wei,A Kumar,ER Dow,TR Stewart,J Shou,M N'cho,DL Sterchi,BD Gitter,RE Higgs,DL Halladay,TA Engler,TJ Martin,HU Bryant,YL Ma,JE Onyia,

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Changes in Osteoblast, Chondrocyte, and Adipocyte Lineages Mediate the Bone Anabolic Actions of PTH and Small Molecule GSK-3 Inhibitor. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Journal of cellular biochemistry

VOLUME: 102

Page Numbers: 1504-18

Journal Abbreviation: J. Cell. Biochem.

ISSN: 0730-2312

DAY: 15

MONTH: Dec

YEAR: 2007

Changes in Osteoblast, Chondrocyte, and Adipocyte Lineages Mediate the Bone Anabolic Actions of PTH and Small Molecule GSK-3 Inhibitor. Information

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LANGUAGE: eng

NlmUniqueID: 8205768

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AFFILIATION: Lilly Research Laboratories, Eli Lilly & Company, Lilly Corporate Center, Indianapolis, Indiana 46285.

Country: United States

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MEDLINETA: J Cell Biochem

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