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Lab Invest. 2016 Jul;96(7):763-72. doi: 10.1038/labinvest.2016.51. Epub 2016 Apr 18.

Apolipoprotein A-1 regulates osteoblast and lipoblast precursor cells in mice.

Author information

1
Pittsburgh VA Medical Center, Pittsburgh, PA, USA.
2
Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA.
3
Department of Anatomy-Histology-Embryology, Unit of Bone and Soft Tissue Studies, University of Patras School of Medicine, Patras, Greece.
4
Department of Mechanical Engineering and Aeronautics, University of Patras, Patras, Greece.
5
Department of Pharmacy, University of Patras, Patras, Greece.
6
Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH/ICE-HT), Patras, Greece.
7
Department of Pharmacology, University of Patras Medical School, Patras, Greece.

Abstract

Imbalances in lipid metabolism affect bone homeostasis, altering bone mass and quality. A link between bone mass and high-density lipoprotein (HDL) has been proposed. Indeed, it has been recently shown that absence of the HDL receptor scavenger receptor class B type I (SR-B1) causes dense bone mediated by increased adrenocorticotropic hormone (ACTH). In the present study we aimed at further expanding the current knowledge as regards the fascinating bone-HDL connection studying bone turnover in apoA-1-deficient mice. Interestingly, we found that bone mass was greatly reduced in the apoA-1-deficient mice compared with their wild-type counterparts. More specifically, static and dynamic histomorphometry showed that the reduced bone mass in apoA-1(-/-) mice reflect decreased bone formation. Biochemical composition and biomechanical properties of ApoA-1(-/-) femora were significantly impaired. Mesenchymal stem cell (MSC) differentiation from the apoA-1(-/-) mice showed reduced osteoblasts, and increased adipocytes, relative to wild type, in identical differentiation conditions. This suggests a shift in MSC subtypes toward adipocyte precursors, a result that is in line with our finding of increased bone marrow adiposity in apoA-1(-/-) mouse femora. Notably, osteoclast differentiation in vitro and osteoclast surface in vivo were unaffected in the knock-out mice. In whole bone marrow, PPARĪ³ was greatly increased, consistent with increased adipocytes and committed precursors. Further, in the apoA-1(-/-) mice marrow, CXCL12 and ANXA2 levels were significantly decreased, whereas CXCR4 were increased, consistent with reduced signaling in a pathway that supports MSC homing and osteoblast generation. In keeping, in the apoA-1(-/-) animals the osteoblast-related factors Runx2, osterix, and Col1a1 were also decreased. The apoA-1(-/-) phenotype also included augmented CEPBa levels, suggesting complex changes in growth and differentiation that deserve further investigation. We conclude that the apoA-1 deficiency generates changes in the bone cell precursor population that increase adipoblast, and decrease osteoblast production resulting in reduced bone mass and impaired bone quality in mice.

PMID:
27088511
DOI:
10.1038/labinvest.2016.51
[Indexed for MEDLINE]
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