Role of Ox-PAPCs in the Differentiation of Mesenchymal Stem Cells and Runx2 and PPAR[gamma]2 Expression in MSCs-Like of Osteoporotic Patients

• Published in: PloS one 2011-06, Vol.6 (6), p.e20363
• Main Authors: Valenti, Maria Teresa, Garbin, Ulisse, Pasini, Andrea, Zanatta, Mirko, Stranieri, Chiara, Manfro, Stefania, Zucal, Chiara, Dalle Carbonare, Luca
• Format: Article
• Language: English
• Subjects: Genes; Genetic aspects; Lipids; Osteoporosis; Stem cells; Transcription (Genetics)
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0020363

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 PPAR[gamma]2 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. Methodology 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 PPAR[gamma]2 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 PPAR[gamma]2 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). Principal findings Quantitative RT-PCR demonstrated that ox-PAPCs enhanced PPAR[gamma]2 and adipogenic gene expression and reduced Runx2 and osteoblast differentiation marker gene expression in differentiating hMSCs. In OPs, ox-PAPC levels and PPAR[gamma]2 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.