title: Role of ox-PAPCs in the differentiation of mesenchymal stem cells (MSCs) and Runx2 and PPARγ2 expression in MSCs-like of osteoporotic patients.
abstract: BACKGROUND
  Mesenchymal stem cells (MSCs) can differentiate into osteoblasts and adipocytes and conditions causing bone loss may induce a switch from the osteoblast to adipocyte lineage. In addition, the expression of Runx2 and the PPARγ2 transcription factor genes is essential for cellular commitment to an osteogenic and adipogenic differentiation, respectively. Modified lipoproteins derived from the oxidation of arachidonate-containing phospholipids (ox-PAPCs: POVPC, PGPC and PEIPC) are considered important factors in atherogenesis.
  
  
  METHODS
  We investigated the effect of ox-PAPCs on osteogenesis and adipogenesis in human mesenchymal stem cells (hMSCs). In particular, we analyzed the transcription factor Runx2 and the PPARγ2 gene expression during osteogenic and adipogenic differentiation in absence and in presence of ox-PAPCs. We also analyzed gene expression level in a panel of osteoblastic and adipogenic differentiation markers. In addition, as circulating blood cells can be used as a "sentinel" that responds to changes in the macro- or micro-environment, we analyzed the Runx2 and the PPARγ2 gene expression in MSCs-like and ox-PAPC levels in serum of osteoporotic patients (OPs). Finally, we examined the effects of sera obtained from OPs in hMSCs comparing the results with age-matched normal donors (NDs).
  
  
  RESULTS
  Quantitative RT-PCR demonstrated that ox-PAPCs enhanced PPARγ2 and adipogenic gene expression and reduced Runx2 and osteoblast differentiation marker gene expression in differentiating hMSCs. In OPs, ox-PAPC levels and PPARγ2 expression were higher than in NDs, whereas Runx2 was lower than in ND circulant MSCs-like.
  
  
  CONCLUSIONS
  Ox-PAPCs affect the osteogenic differentiation by promoting adipogenic differentiation and this effect may appear involved in bone loss in OPs.
authors.affiliation: Department of Medicine, Clinica di Medicina Interna, Sezione D, University of Verona, Verona, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Valenti
authors.forename: Ulisse
authors.initials: U
authors.lastname: Garbin
authors.forename: Andrea
authors.initials: A
authors.lastname: Pasini
authors.forename: Mirko
authors.initials: M
authors.lastname: Zanatta
authors.forename: Chiara
authors.initials: C
authors.lastname: Stranieri
authors.forename: Stefania
authors.initials: S
authors.lastname: Manfro
authors.forename: Chiara
authors.initials: C
authors.lastname: Zucal
authors.forename: Luca
authors.initials: L
authors.lastname: Dalle Carbonare
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000187:drug effects*; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics*; D003720:Densitometry; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D010012:Osteogenesis / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000235:genetics / Q000473:pathology*; D047495:PPAR gamma / Q000235:genetics*; D010641:Phenotype; D010713:Phosphatidylcholines / Q000097:blood / Q000494:pharmacology*; D044967:Serum / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D047495:PPAR gamma; D010713:Phosphatidylcholines; C472349:oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine