Related Experiment Video
Updated: Jun 5, 2025
Prospective, Randomized, and Controlled Study of a Human Umbilical Cord Mesenchymal Stem Cell Injection for Treating Diabetic Foot Ulcers
Published on: March 3, 2023
Scutellarin Alleviates Bone Marrow Mesenchymal Stromal Cellular Senescence via the Ezh2-Nrf2 Signalling Axis in
Tiantian Wang1,2,3, Jiehao Chen4, Bo Qu5
1Department of Neurology, Institute of Neurology and Disease, West China Hospital of Sichuan University, Chengdu, China.
Abstract:
Currently, there is no specific treatment for diabetes-induced osteoporosis (DOP). Our study identified diabetes-induced cellular senescence, marked by elevated activity of senescence-associated β-galactosidase. Targeting senescent cells holds promise for osteoporosis treatment. We demonstrated that scutellarin (SCU) effectively mitigated bone loss in DOP mice, and co-treatment with SCU significantly reduced diabetes-induced senescence in LepR+MSCs. Furthermore, our research highlighted the role of Nrf2 in SCU's anti-senescence effects on bone. The deletion of Nrf2 impaired SCU's ability to alleviate DOP. Mechanistically, SCU enhances Ezh2 expression and increases H3K27me3 activity at the Keap1 promoter region, leading to Keap1 repression and enhanced Nrf2-ARE signalling. Additionally, SCU notably inhibited cellular senescence and diabetes-related osteoporosis, these effects were significantly reduced in Ezh2LepRcre conditional knockout models. These findings suggest that the Ezh2-Nrf2 signalling axis is crucial for mediating SCU's beneficial effects in this context. Overall, our discoveries provide insights into the mechanisms underlying DOP and propose a potential preventive strategy for this condition.
Insights
Scutellarin (SCU) effectively treats osteoporosis in diabetes by targeting senescent cells. It works by activating the Ezh2-Nrf2 pathway, offering a potential new strategy for diabetes-induced osteoporosis.
Area of Science:
- Biomedical Science
- Cellular Biology
- Endocrinology
Background:
- Diabetes-induced osteoporosis (DOP) lacks specific treatments.
- Cellular senescence is a key factor in DOP development.
- Targeting senescent cells presents a therapeutic opportunity.
Purpose of the Study:
- To investigate the therapeutic potential of scutellarin (SCU) for DOP.
- To elucidate the mechanisms underlying SCU's effects on bone health in diabetes.
- To identify key molecular pathways involved in SCU's anti-osteoporosis action.
Main Methods:
- Utilized a mouse model of diabetes-induced osteoporosis.
- Assessed cellular senescence markers, including senescence-associated β-galactosidase.
- Investigated the role of Nrf2 and Ezh2 signaling pathways.
- Employed LepR+MSCs and Ezh2 conditional knockout models.
Main Results:
- Scutellarin (SCU) significantly mitigated bone loss in DOP mice.
- SCU reduced diabetes-induced senescence in LepR+MSCs.
- SCU's protective effects were dependent on Nrf2 and Ezh2 activity.
- SCU enhanced Ezh2 expression, leading to Keap1 repression and Nrf2 activation.
Conclusions:
- The Ezh2-Nrf2 signaling axis is critical for SCU's therapeutic effects in DOP.
- SCU demonstrates potential as a preventive and therapeutic agent for diabetes-induced osteoporosis.
- Targeting cellular senescence via the Ezh2-Nrf2 pathway offers a novel strategy for DOP treatment.
