The role of Zfp467 in mediating the pro-osteogenic and anti-adipogenic effects on bone and bone marrow niche

Conditional deletion of the PTH receptor (Pth1r) in mesenchymal progenitors reduces osteoblast differentiation and bone mass while enhancing adipogenesis and bone marrow adipose tissue. Mechanistically, PTH suppresses the expression of Zfp467, a pro-adipogenic zinc finger transcription factor. Consequently, Pth1r deficiency in mesenchymal progenitors leads to increased Zfp467 expression. Based on these observations, we hypothesized that genetic loss of Zfp467 would lead to a shift in marrow progenitor cell fate towards osteogenesis and increased bone mass. To test this hypothesis, we generated Zfp467−/− mice. Zfp467−/− mice (−/−) were significantly smaller than Zfp467+/+ mice (+/+). μCT showed significantly higher trabecular bone and cortical bone area in −/− vs. +/+, and histomorphometry showed higher structural and dynamic formation parameters in −/− mice vs. +/+. Femoral gene expression including Alpl, Sp7, and Acp5 were increased in −/−mice, whereas Adiponectin, Cebpa, Lepr, and Ppraγ mRNA were lower in −/− mice. Similarly, Fabp4 and Lep in the inguinal depot were also decreased in −/− mice. Moreover, marrow adipocyte numbers were reduced in −/− vs +/+ mice (p