Pitx1

Pitx1 knockout reduces height.

All-trans-retinoid acid (ATRA) may have inhibited chondrogenesis of primary hind limb bud mesenchymal cells by downregulating Pitx1 expression.

"Pitx1, which is expressed in the hindlimb bud mesenchyme, or its pathways may be etiologically responsible for the increased incidence of clubfoot. Here, we sought to investigate the mechanisms whereby Pitx1 regulated chondrogenesis of hindlimb bud mesenchymal cells in vitro. E12.5 embryonic rat hind limb bud mesenchymal cells were treated with ATRA at appropriate concentrations. Cell Counting Kit-8 (CCK-8) assay was performed to evaluate cell proliferation. Hematoxylin-safranin-O-fast-green staining assays were used to observe cartilage nodules, and Pitx1 expression was examined by immunofluorescent microscopy. Real-time quantitative PCR and immunoblotting assays were applied to determine the mRNA expressions of Pitx1, Sox9 and type II collagen (Col2al), respectively. ATRA inhibited the proliferation of hind limb bud cells dose-dependently. ATRA also induced a dose-dependent reduction in the number of cartilage nodules and the area of cartilage nodules compared with controls. The mRNA expression of Pitx1, Sox9 and Col2al were significantly downregulated by ATRA. Pitx1 was mainly expressed in the cartilage nodules and the levels of Pitx1, Sox9 and Col2al were also downregulated by ATRA dose-dependently. ATRA may decrease chondrogenesis of hind limb bud mesenchymal cells by inhibiting cartilage-specific molecules, such as Sox9 and Col2al, via downregulating Pitx1 expression."

" loss of Pitx1 expression in the developing mouse causes the hindlimb to assume the morphology and growth features of the corresponding bones in the forelimb"

"1 μM ATRA caused a 25% reduction at 24 h and a 25% reduction at 48 h in the growth of the mesenchymal cells compared to controls. Furthermore, 10 μM ATRA caused a 75% reduction at 24 h and a 75% reduction at 48 h in the growth of the mesenchymal cells compared to controls"

"Pitx1 was expressed in the cartilage nodules, mainly in the nucleus"

0.01 microM of ATRA did not have a chondroinhibitory effect.

"ATRA dose-dependently reduced the number of cartilage nodules and the area of cartilage nodules in rat hind limb bud"