title: Apolipoprotein D deficiency is associated to high bone turnover, low bone mass and impaired osteoblastic function in aged female mice.
abstract: Apolipoprotein D (ApoD) is a member of the lipocalin family known to transport small hydrophobic ligands. A major site of ApoD expression in mice is the central nervous system where evidence suggests that it plays a protective role. Gene expression of ApoD was reported in bone-forming osteoblasts but its impact on bone metabolism remains undocumented.
  
  
  
  We compared basic bone parameters of ApoD(-/-) (null) and transgenic (tg) mice to wild-type (wt) littermates through microCT and histochemistry, as well as ApoD expression and secretion in osteoblasts under various culture conditions through real-time PCR and immunoblotting.
  
  
  
  ApoD-null females displayed progressive bone loss with aging, resulting in a 50% reduction in trabecular bone volume and a 23% reduction in cortical bone volume by 9months of age. Only cortical bone volume was significantly reduced in ApoD-null males by an average of 24%. Histochemistry indicated significantly higher osteoblast surface and number of osteoclasts in femora from ApoD-null females. ApoD gene expression was confirmed in primary cultures of bone marrow mesenchymal cells (MSC), with higher expression levels in MSC from females compared to males. ApoD-null MSC exhibited impaired proliferation and differentiation potentials. Moreover, exogenous ApoD partially rescued the osteogenic potential of null MSC, which were shown to readily uptake the protein from media. ApoD expression was upregulated under low proliferation conditions, by contact inhibition and osteoblastic differentiation in MC3T3-E1 osteoblast-like cells.
  
  
  
  Our results indicate that ApoD influences bone metabolism in mice in a gender-specific manner, potentially through an auto-/paracrine pathway.
authors: Laboratoire du Métabolisme Osseux, Centre BioMed, Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada. Electronic address: cmartineau@shriners.mcgill.ca.
authors: Corine
authors: C
authors: Martineau
authors: Laboratoire de Biologie Moléculaire, Centre BioMed, Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada.
authors: Ouafa
authors: O
authors: Najyb
authors: Laboratoire du Métabolisme Osseux, Centre BioMed, Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada.
authors: Céline
authors: C
authors: Signor
authors: Laboratoire de Biologie Moléculaire, Centre BioMed, Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada.
authors: Éric
authors: É
authors: Rassart
authors: Laboratoire du Métabolisme Osseux, Centre BioMed, Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Québec, Canada.
authors: Robert
authors: R
authors: Moreau
mesh_terms: D016475:3T3 Cells; D000375:Aging / Q000235:genetics*; D000818:Animals; D053399:Apolipoproteins D / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D001846:Bone Development / Q000235:genetics*; D001854:Bone Marrow Cells / Q000378:metabolism; D016723:Bone Remodeling / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D005269:Femur / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism; D061251:Primary Cell Culture
chemical_list: D053399:Apolipoproteins D
keywords: Apolipoprotein D; Differentiation; Low bone mass; Osteoblast; Proliferation