YAP-dependent transcriptional responses in tenocytes under cyclic tensile loading: a conditional knockout RNA-sequencing study
- 1Department of Orthopaedics, Tianjin First Central Hospital , ,
- 2Orthopedic Soft Tissue Research Program, Hospital for Special Surgery , , ,
- 3Performance Medicine Institute , , ,
Abstract
Background
Tendon injuries are prevalent across various populations and significantly impair quality of life, presenting substantial healthcare challenges.Purpose
This study aimed to characterize Yes-associated protein (YAP) -dependent transcriptional responses in tenocytes under cyclic tensile loading, using a conditional YAP knockout approach combined with RNA sequencing. Given that tenocytes in vivo are continuously exposed to mechanical loading, this design was intended to identify genes whose regulation by YAP becomes critical under mechanical challenge.Methods
Employing conditional gene knockout techniques with RosaCreERT2 YAP-floxed mice and mechanical loading protocols, alongside RNA sequencing and advanced bioinformatics analyses.Results
We identified 54 differentially expressed genes (DEGs) in tenocytes after YAP knockout, including six upregulated and 48 downregulated genes. Notably, upregulated genes included Gzmc and Gm28151, while downregulated genes included Car3 and Rgs2. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted significant pathways, such as the PPAR signaling pathway, emphasizing their relevance in tendon pathophysiology. Furthermore, CIBERSORTx analysis revealed significant differences in immune cell infiltration, particularly in Treg and CD4 naive T cells, suggesting a link between YAP-dependent pathways and immune responses in tendon healing. Drug prediction analyses identified several small molecules interacting with hub genes, including LTC4S and CXCL13, indicating potential pharmacological targets for therapeutic intervention.Conclusion
Despite limitations such as a lack of in vivo validation and small sample size, this research underscores the pivotal role of YAP in tenocyte mechanotransduction and identifies key DEGs and pathways that may inform future therapeutic strategies for tendon injuries. Future studies should focus on the in-vivo implications of these findings and explore the potential for immune modulation and pharmacological interventions in tendon repair.
Related
- Multi-omics analysis reveals coordinated transcriptional and epigenetic remodeling of tenocytes under IL-1β-driven inflammatory stimulation
- Sex-dependent transcriptional and imaging responses to metformin in young-adult mice with SuHx-induced pulmonary arterial hypertension
- Blood and Urine Transcriptomes Reveal Complementary Host Responses and a Creatinine-Associated Urinary Transcriptional Axis in Sepsis
- Physiological and Transcriptional Responses of the Blood Clam Anadara kagoshimensis (Tokunaga, 1906) During Cadmium Exposure.
- Transcriptional cyclin-dependent kinases as therapeutic targets in bone metastasizing cancers
BibTeX
@article{xing2026yapdependent,
title = {{YAP-dependent transcriptional responses in tenocytes under cyclic tensile loading: a conditional knockout RNA-sequencing study}},
author = {Xuewu Xing and Alexander Piacentini and Yuki Suzuki and Leonardo A. Sanchez and Chris Mendias and Scott A. Rodeo},
journal = {Frontiers in bioengineering and biotechnology},
year = {2026},
month = oct,
doi = {10.3389/fbioe.2026.1901935},
url = {https://europepmc.org/article/PMC/PMC13716730},
note = {CC BY},
}
RIS
TY - JOUR
TI - YAP-dependent transcriptional responses in tenocytes under cyclic tensile loading: a conditional knockout RNA-sequencing study
AU - Xuewu Xing
AU - Alexander Piacentini
AU - Yuki Suzuki
AU - Leonardo A. Sanchez
AU - Chris Mendias
AU - Scott A. Rodeo
PY - 2026
DA - 2026/10/15
JO - Frontiers in bioengineering and biotechnology
DO - 10.3389/fbioe.2026.1901935
UR - https://europepmc.org/article/PMC/PMC13716730
AB - Background Tendon injuries are prevalent across various populations and significantly impair quality of life, presenting substantial healthcare challenges.Purpose This study aimed to characterize Yes-associated protein (YAP) -dependent transcriptional responses in tenocytes under cyclic tensile loading, using a conditional YAP knockout approach combined with RNA sequencing. Given that tenocytes in vivo are continuously exposed to mechanical loading, this design was intended to identify genes whose regulation by YAP becomes critical under mechanical challenge.Methods Employing conditional gene knockout techniques with RosaCreERT2 YAP-floxed mice and mechanical loading protocols, alongside RNA sequencing and advanced bioinformatics analyses.Results We identified 54 differentially expressed genes (DEGs) in tenocytes after YAP knockout, including six upregulated and 48 downregulated genes. Notably, upregulated genes included Gzmc and Gm28151, while downregulated genes included Car3 and Rgs2. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses highlighted significant pathways, such as the PPAR signaling pathway, emphasizing their relevance in tendon pathophysiology. Furthermore, CIBERSORTx analysis revealed significant differences in immune cell infiltration, particularly in Treg and CD4 naive T cells, suggesting a link between YAP-dependent pathways and immune responses in tendon healing. Drug prediction analyses identified several small molecules interacting with hub genes, including LTC4S and CXCL13, indicating potential pharmacological targets for therapeutic intervention.Conclusion Despite limitations such as a lack of in vivo validation and small sample size, this research underscores the pivotal role of YAP in tenocyte mechanotransduction and identifies key DEGs and pathways that may inform future therapeutic strategies for tendon injuries. Future studies should focus on the in-vivo implications of these findings and explore the potential for immune modulation and pharmacological interventions in tendon repair.
SN - 2296-4185
ER -