BACKGROUND: Growing evidence supports a key role for @entity32 in the onset and progression of @entity924 . However, the effect of the inflammatory infiltrate on tendon cells is poorly understood. METHODS: We investigated stromal fibroblast activation signatures in tissues and cells from @entity1 with @entity924 . Diseased tendons were collected from well-phenotyped @entity1 cohorts with @entity924 before and after sub-acromial decompression treatment. Healthy tendons were collected from @entity1 undergoing shoulder stabilisation or anterior cruciate ligament repair. Stromal fibroblast activation markers including podoplanin ( @entity13712 ), @entity4725 ( @entity4725 ) and @entity25054 were investigated by immunostaining, flow cytometry and RT-qPCR. RESULTS: @entity13712 , @entity25054 and @entity4725 were increased in diseased compared to healthy tendon tissues. This stromal fibroblast activation signature persisted in tendon biopsies in @entity1 at 2-4 years post treatment. @entity13712 , @entity25054 and @entity4725 were increased in diseased compared to healthy tendon cells. @entity1356 treatment induced @entity13712 and @entity4725 but not @entity25054 . @entity1356 treatment induced NF-kB target genes in healthy cells, which gradually declined following replacement with cytokine-free medium, whilst @entity13712 and @entity4725 remained above pre-stimulated levels. @entity1356 -treated diseased cells had more profound induction of @entity13712 and @entity4725 and sustained expression of @entity650 and @entity687 mRNA compared to @entity1356 -treated healthy cells. CONCLUSIONS: We conclude that stromal fibroblast activation markers are increased and persist in diseased compared to healthy tendon tissues and cells. Diseased tendon cells have distinct stromal fibroblast populations. @entity1356 treatment induced persistent stromal fibroblast activation which was more profound in diseased cells. Persistent stromal fibroblast activation may be implicated in the development of @entity32 and recurrent @entity924 . Targeting this stromal fibroblast activation signature is a potential therapeutic strategy.

Persistent stromal fibroblast activation is present in chronic XXXX .

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity32 :: ('MESH:D007249', 'Disease') :: ['chronic inflammation', 'inflammation'] @entity650 :: ('3569', 'Gene') :: ['IL6'] @entity1356 :: ('3553', 'Gene') :: ['IL-1b'] @entity924 :: ('MESH:D052256', 'Disease') :: ['tendinopathy', 'supraspinatus tendinopathy'] @entity13712 :: ('10630', 'Gene') :: ['PDPN'] @entity4725 :: ('7412', 'Gene') :: ['CD106', 'VCAM-1'] @entity687 :: ('3576', 'Gene') :: ['IL8'] @entity25054 :: ('57124', 'Gene') :: ['CD248']
@entity924 :: (MESH:D052256,Disease) :: ['tendinopathy']
