Summary
This research project investigates the biological mechanisms that promote tendon repair versus degeneration after fatigue injury, focusing on the roles of glycosaminoglycans (GAGs), αSMA+ cells, and integrin α5.
Promoting a reparative instead of a degenerative outcome from loading of fatigue-damaged tendons
US · IL
NIH RePORTER
grant
awarded
#nih-5R01AR084173-02
What they want
The project aims to test three hypotheses: (1) the increase in GAGs after fatigue injury modulates the mechanical environment of cells in damaged tendons, leading to an increase in αSMA+ cells and integrin α5; (2) the increase in αSMA+ cells will largely decrease the area of high matrix damage and mediate tissue repair; and (3) integrin α5 protects cells from apoptosis in response to higher loading but promotes a catabolic response from surviving α5+/tenocytes while enhancing the functionality of α5+/αSMA+ cells. Experimental approaches include in vivo depletion of hyaluronan (HA) and dermatan sulfate (DS), pharmaceutical inhibition of αSMA+ cells (using Simvastatin) and integrin α5 (using ATN-161), and scRNAseq to compare cell populations associated with repair versus degeneration.
Deliverables
- Inform diagnostics to guide management of tendon injuries
- Inform therapeutics by determining key biological drivers of repair
Technical requirements
- In vivo model of sub-rupture fatigue damage accumulation using the rat patellar tendon
- Depletion of HA and DS in vivo
- Pharmaceutical inhibition of αSMA+ cells (using Simvastatin)
- Pharmaceutical blocking of integrin α5 (using ATN-161)
- scRNAseq for cell population comparison
