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Monitoring Endoplasmic Reticulum Peroxynitrite Fluctuations in Primary Tendon-Derived Stem Cells and Insights into
Huimin Liu1, Min Zhu1, Haihui Yang2
1Department of Orthopedic Surgery and Orthopedic Research Institute, Stem Cell and Tissue Engineering Research Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China.
ACS Sensors
|November 14, 2024
Summary
Researchers developed fluorescent probes to detect peroxynitrite (ONOO-) in endoplasmic reticulum (ER) stress, crucial for understanding tendinopathy progression and developing new treatments.
Area of Science:
- Biomedical Engineering
- Stem Cell Biology
- Musculoskeletal Research
Background:
- Tendinopathy is a common musculoskeletal disorder impacting patient quality of life.
- Reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress influence tendon-derived stem cell (TDSC) differentiation, contributing to tendinopathy.
- The role of peroxynitrite (ONOO-) in TDSC differentiation and tendinopathy stages is largely unknown.
Purpose of the Study:
- To develop and validate fluorescent probes for detecting ONOO- in the ER.
- To investigate the relationship between ONOO-, TDSC differentiation, and ER stress.
- To explore ONOO- dynamics in tendinopathy models.
Main Methods:
- Development of two specific fluorescent probes (Rod-Cl and Rod-Br) for ER ONOO- detection.
- Measurement of basal and stimulated ONOO- levels in TDSCs using Rod-Br.
- Assessment of ONOO- variations in in vitro TDSC differentiation and in vivo tendinopathy rat models.
Main Results:
- Rod-Br successfully detected basal ONOO- levels in TDSC ER.
- ONOO- levels correlated with interleukin-1β stimulation, differentiation pathways (chondrogenic/osteogenic), and ER stress.
- Significant ONOO- variations were observed across different tendinopathy stages and treatment responses in vivo.
Conclusions:
- Novel fluorescent probes provide a tool to analyze ONOO- dynamics in TDSC differentiation.
- Findings offer new insights into the pathophysiology of tendinopathy involving ONOO- and ER stress.
- This research may aid in developing targeted interventions for tendinopathy.
