miR-135a modulates tendon stem/progenitor cell senescence via suppressing ROCK1

Area of Science:

• Biomedical Science
• Cellular Biology
• Regenerative Medicine

Background:

• Tendon stem/progenitor cell (TSPC) senescence contributes to age-related tendon disorders and impairs healing.
• The molecular mechanisms underlying TSPC aging and degeneration are not fully understood.
• Rho-associated coiled-coil protein kinase 1 (ROCK1) and microRNAs (miRNAs) are implicated in cellular senescence.

Purpose of the Study:

• To investigate whether specific miRNAs modulate TSPC senescence by targeting ROCK1.
• To elucidate the role of miR-135a in the aging process of TSPCs.
• To determine if ROCK1 mediates the effects of miR-135a on TSPC function.

Main Methods:

• Quantitative real-time PCR to measure miR-135a levels in young and aged TSPCs.
• Luciferase reporter assay to confirm direct binding of miR-135a to the ROCK1 3'-untranslated region.
• Gain-of-function and loss-of-function experiments involving miR-135a and ROCK1 in TSPCs.
• Assessment of TSPC senescence, proliferation, migration, and tenogenic differentiation.

Main Results:

• miR-135a was significantly downregulated in aged TSPCs compared to young TSPCs.
• Overexpression of miR-135a in young TSPCs reduced senescence markers and enhanced proliferation, migration, and tenogenic differentiation.
• Suppression of miR-135a in aged TSPCs exacerbated senescence and impaired these functions.
• ROCK1 was identified as a direct target of miR-135a, and it mediated the observed effects of miR-135a on TSPCs.

Conclusions:

• miR-135a plays a critical role in regulating TSPC senescence.
• The miR-135a/ROCK1 axis is a key pathway involved in TSPC aging.
• Targeting miR-135a may offer a therapeutic strategy for age-related tendon disorders and improving tendon regeneration.