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. 2011 Dec;31(23):4692–4705. doi: 10.1128/MCB.05979-11

Fig. 7.

Fig. 7.

PPARγ promotes osteoclast progenitors by activating GATA2 transcription. (A) GATA2/GATA1 mRNA ratio in GFP+ and GFP− bone marrow populations (n = 2). The error bars indicate SD. (B) GATA2 and GATA1 mRNA expression (n = 2). (C) Alignment of mouse (m), rat (r), and human (h) GATA2 promoter PPRE regions, together with known PPREs for ap2, PEPCK, ACS, and DR-1 consensus. (D) ChIP analysis of PPARγ or PU.1 binding and histone H3 acetylation in the mGATA2 promoter PPRE regions in GFP− and GFP+ bone marrow cells. For P values, the asterisks (or n.s.) compare each antibody with IgG control in the same cell population; the pluses compare the same antibody in GFP+ cells with GFP− cells (n = 3). (E) Osteoclast differentiation blockade in PPARγ− cells was partially rescued by ectopic GATA2 expression. Hematopoietic bone marrow cells were transfected with GATA2-expressing plasmid or vector control. Osteoclast differentiation was quantified by TRAP expression (left), and GATA2 protein was quantified by Western blotting (IB) (right). The P values compare GATA2-transfected GFP− cells with vector-transfected GFP− cells; GFP+ cells served as a positive control. (F) RANKL-induced and BRL-stimulated osteoclast differentiation in PPARγ+ cells was severely diminished by GATA2 knockdown. Hematopoietic bone marrow cells were transfected with GATA2 siRNA (siGATA2) or control siRNA (siCtrl). Osteoclast differentiation was quantified by TRAP expression (left), and GATA2 protein was quantified by Western blotting (right). The P values compare siGATA2-transfected GFP+ cells with siCtrl-transfected GFP+ cells; GFP− cells served as a negative control. (G) Model for PPARγ regulation of osteoclastogenesis. PPARγ expression promotes osteoclast progenitor specification by activating GATA2 transcription. Upon PPARγ agonist availability, the ligand-activated PPARγ/RXRα receptor complex recruits coactivator PGC1β and induces c-fos transcription, thereby stimulating RANKL-mediated osteoclast differentiation. HSC, hematopoietic stem cells. * or +, P < 0.05; ** or ++, P < 0.01; *** or +++, P < 0.005; ****, P < 0.001; ***** or +++++, P < 0.0005; ****** or ++++++, P < 0.0001; n.s., nonsignificant (P > 0.05).