Core Concepts
Tgif1 is essential for osteoblasts to adapt a regular cell morphology, efficiently adhere and migrate on collagen type I-rich matrices, and activate bone surfaces during bone regeneration and in response to parathyroid hormone treatment.
Abstract
This study demonstrates that deficiency of the transcriptional regulator Tgif1 in osteoblasts results in altered cell morphology, reduced adherence to collagen type I-coated surfaces, and impaired migration capacity. Tgif1 acts as a transcriptional repressor of p21-activated kinase 3 (PAK3), an important regulator of focal adhesion formation and osteoblast spreading. Absence of Tgif1 leads to increased PAK3 expression, which impairs osteoblast spreading.
The findings also show that Tgif1 is important for osteoblast recruitment and activation of bone surfaces during bone regeneration and in response to parathyroid hormone (PTH) treatment. PTH promotes osteoblast spreading via Tgif1-PAK3 signaling, with PAK3 expression being reduced by PTH treatment in a Tgif1-dependent manner.
Overall, this study emphasizes the importance of Tgif1 in regulating osteoblast morphology, adherence, and migration through the modulation of PAK3 expression, providing novel insights into the regulation of the cytoskeletal architecture of osteoblasts, which is crucial for bone remodeling, regeneration, and the pharmacological effects of PTH.
Stats
Tgif1-deficient osteoblasts exhibited a shorter track length, reduced migration velocity, and more meandering migration paths compared to control cells.
Tgif1-deficient osteoblasts had a reduced cell area and perimeter compared to control cells.
Tgif1 deficiency led to a reduced number and activity of osteoblasts during bone regeneration.
PTH treatment increased the number of active osteoblasts and the percentage of active bone surfaces to a much lesser extent in mice lacking Tgif1.
Quotes
"Tgif1 is essential for osteoblasts to adapt a regular cell morphology and to efficiently adhere and migrate on collagen type I-rich matrices in vitro."
"Absence of Tgif1 leads to increased PAK3 expression, which impairs osteoblast spreading."
"PTH promotes osteoblast spreading via Tgif1-PAK3 signaling, with PAK3 expression being reduced by PTH treatment in a Tgif1-dependent manner."