English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

The cellular and molecular mechanisms underlying senile osteoporosis remain poorly understood. In this study, transgenic  mCol1α1-Pitx1  mice overexpressing paired-like homeodomain 1 (PITX1), a homeobox transcription factor, rapidly develop a severe type-II osteoporotic phenotype with significant reduction in bone mass and biomechanical strength similar to that seen in humans and reminiscent of the phenotype previously observed in  Sca-1  ( Ly6a )-null mice. PITX1 plays a critical role in hind limb formation during fetal development, while loss of expression is associated with primary knee/hip osteoarthritis in aging humans. Through  in vivo  and  in vitro  analyses, we demonstrate that  Pitx1  directly regulates the self-renewal of mesenchymal progenitors and indirectly regulates osteoclast differentiation through the upregulation of Wnt signaling inhibitors  DKK1 ,  SOST , and  GSK3-β . This is confirmed by elevated levels of plasma DKK1 and the accumulation of phospho-β-catenin in transgenic mice osteoblasts. Furthermore, overexpressed  Pitx1  in mice osteoblasts results in severe repression of  Sca-1  ( Ly6a ) that was previously associated with senile osteoporosis. Our study is the first to demonstrate the novel roles of PITX1 in senile osteoporosis where PITX1 regulates the self-renewal of mesenchymal stem cells or progenitor cells through  Sca-1 (Ly6a)  repression and, in addition, inhibits the Wnt signaling pathway.

scientific reports

Bone-Specific Overexpression of PITX1 Induces Senile Osteoporosis in Mice Through Deficient Self-Renewal of Mesenchymal Progenitors and Wnt Pathway Inhibition