Prim-O-Glucosylcimifugin Repairs Diabetic Tendon Injury by Rescuing Tendon Stem/Progenitor Cell Hypofunction Through...

Area of Science:

• Biomedical Engineering
• Regenerative Medicine
• Diabetology

Background:

• Diabetes mellitus significantly increases the risk of tendon disorders, including tendinopathy and impaired healing.
• Tendon stem/progenitor cells (TSPCs) are vital for tendon homeostasis and repair, but their function is compromised in diabetic conditions.
• Current treatments for diabetic tendon injuries are limited, highlighting the need for novel therapeutic strategies.

Purpose of the Study:

• To investigate the efficacy of prim-O-glucosylcimifugin (POG) in mitigating high glucose-induced senescence in TSPCs.
• To evaluate POG's potential to restore the regenerative capacity of TSPCs under diabetic conditions.
• To assess POG's therapeutic effect on tendon healing in a diabetic mouse model.

Main Methods:

• High glucose (HG) stimulation was used to induce senescence in TSPCs in vitro.
• POG treatment was applied to assess its effects on TSPC senescence markers, self-renewal, and tenogenic differentiation.
• Mesoporous silica nanoparticles were utilized for local POG delivery in diabetic mice with induced tendon injuries.
• The combination of POG and biomimetic scaffold transplantation was evaluated for its effects on tendon regeneration.

Main Results:

• HG stimulation induced TSPC senescence, marked by reduced self-renewal, increased senescence markers, and impaired tenogenic differentiation.
• POG treatment effectively counteracted HG-induced TSPC senescence and restored tenogenic differentiation potential via AMPK pathway activation.
• In vivo, local POG delivery via nanoparticles significantly promoted tendon healing in diabetic mice.
• Combined POG treatment and scaffold transplantation functionally rescued tendon regeneration and repair in diabetic mice.

Conclusions:

• Pharmacological intervention with POG can rescue high glucose-induced TSPC dysfunction.
• POG demonstrates significant potential in promoting tendon healing in diabetic conditions.
• POG represents a promising therapeutic agent for managing tendon disorders in diabetic patients.