Related Experiment Video
Updated: Jun 24, 2025
Culturing and Manipulation of O9-1 Neural Crest Cells
Published on: October 9, 2018
YAP promotes the early development of temporomandibular joint bony ankylosis by regulating mesenchymal stem cell
Tong-Mei Zhang1,2,3,4, Mai-Ning Jiao5, Kun Yang6
1Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, West Huan-Hu Road, Ti Yuan Bei, Hexi District, Tianjin, 30060, China.
Abstract:
To explore the role of YAP, a key effector of the Hippo pathway, in temporomandibular joint (TMJ) ankylosis. The temporal and spatial expression of YAP was detected via immunohistochemistry and multiplex immunohistochemistry on postoperative Days 1, 4, 7, 9, 11, 14 and 28 in a sheep model. Isolated mesenchymal stem cells (MSCs) from samples of the Day 14. The relative mRNA expression of YAP was examined before and after the osteogenic induction of MSCs. A YAP-silenced MSC model was constructed, and the effect of YAP knockdown on MSC function was examined. YAP is expressed in the nucleus of the key sites that determine the ankylosis formation, indicating that YAP is activated in a physiological state. The expression of YAP increased gradually over time. Moreover, the number of cells coexpressing of RUNX2 and YAP-with the osteogenic active zone labelled by RUNX2-tended to increase after Day 9. After the osteogenic induction of MSCs, the expression of YAP increased. After silencing YAP, the osteogenic, proliferative and migratory abilities of the MSCs were inhibited. YAP is involved in the early development of TMJ bony ankylosis. Inhibition of YAP using shRNA might be a promising way to prevent or treat TMJ ankylosis.
Insights
The Yes-associated protein (YAP) is activated during temporomandibular joint (TMJ) ankylosis development. Inhibiting YAP in mesenchymal stem cells (MSCs) reduces their function, suggesting YAP as a therapeutic target for TMJ ankylosis.
Area of Science:
- Molecular Biology
- Cell Biology
- Orthopedics
Background:
- Temporomandibular joint (TMJ) ankylosis is a debilitating condition characterized by the fusion of the jawbone.
- The Hippo pathway, regulated by Yes-associated protein (YAP), plays a crucial role in tissue development and regeneration.
- Understanding YAP's role in TMJ ankylosis could reveal new therapeutic targets.
Purpose of the Study:
- To investigate the expression and function of YAP in the development of TMJ ankylosis.
- To assess the potential of YAP inhibition as a therapeutic strategy for TMJ ankylosis.
Main Methods:
- Utilized a sheep model to examine YAP expression via immunohistochemistry at various time points post-surgery.
- Isolated mesenchymal stem cells (MSCs) and analyzed YAP mRNA expression before and after osteogenic induction.
- Constructed a YAP-silenced MSC model to evaluate the impact of YAP knockdown on MSC functions.
Main Results:
- YAP was found to be activated in the nucleus at key sites of TMJ ankylosis formation, with expression increasing over time.
- Co-expression of YAP and RUNX2 (an osteogenic marker) increased after postoperative Day 9.
- YAP silencing in MSCs inhibited their osteogenic, proliferative, and migratory abilities.
Conclusions:
- YAP is actively involved in the early stages of TMJ bony ankylosis development.
- Inhibiting YAP, potentially using shRNA, shows promise as a therapeutic approach for preventing or treating TMJ ankylosis.
