Persistent stromal fibroblast activation is present in chronic tendinopathy

Area of Science:

• Biomedical Science
• Cell Biology
• Orthopedics

Background:

• Inflammation plays a role in tendinopathy development and progression.
• The impact of inflammatory infiltrates on tendon cells remains unclear.

Purpose of the Study:

• To investigate stromal fibroblast activation signatures in tendinopathy tissues and cells.
• To understand the cellular response to inflammation in diseased tendons.

Main Methods:

• Analyzed supraspinatus tendinopathy tissues and cells from patients before and after treatment.
• Compared diseased tendons with healthy tendons from control patients.
• Assessed stromal fibroblast activation markers (podoplanin, CD106, CD248) using immunostaining, flow cytometry, and RT-qPCR.
• Investigated the effect of IL-1β treatment on tendon cells.

Main Results:

• Increased PDPN, CD248, and CD106 in diseased tendon tissues and cells compared to healthy.
• Persistent activation signature observed in post-treatment biopsies (2-4 years).
• Diseased tendon cells exhibited a more profound and sustained response to IL-1β treatment, including increased IL6 and IL8 mRNA expression.

Conclusions:

• Stromal fibroblast activation markers are elevated and persistent in tendinopathy.
• Distinct stromal fibroblast populations exist in diseased tendons.
• Persistent stromal fibroblast activation, particularly in response to IL-1β, may drive chronic inflammation and recurrent tendinopathy.
• Targeting stromal fibroblast activation presents a potential therapeutic strategy.