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Rapamycin limits peritendinous fibrosis but does not affect intratendinous healing in a rodent Achilles tendon injury model

ABSTRACT: Tendon injuries are common, affecting both athletes and the general population. Healing is often poor, with deposition of fibrotic, disorganised scar-like tissue leading to continued pain, dysfunction and reinjury. While a variety of therapeutics are available clinically to treat tendon injuries, outcomes remain variable and no treatments are able to fully restore tendon structure and function, hence novel regenerative therapies are required. The pathogenesis of many fibrotic diseases is influenced by the mammalian target of rapamycin (mTOR) signalling pathway, which modulates processes required for cell growth and proliferation. Rapamycin, an mTOR inhibitor, is a promising therapeutic for several fibrotic diseases, and can facilitate musculoskeletal tissue repair. Therefore, we used a needle injury model in the rat Achilles tendon to test the hypothesis that rapamycin treatment during the early stages of tendon injury enhances tendon healing via modulation of resident tendon cell populations and autophagy. The results demonstrate that, while rapamycin treatment decreased peritendinous fibrosis and appeared to modulate cell recruitment, it did not enhance healing of lesions within the tendon core, up to three weeks post-injury. Therefore, rapamycin is not an effective therapeutic for tendon injury in young adults. Future studies should establish if rapamycin is able to improve tendon healing in aged animals or with longer-term administration.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE293831 | GEO | 2025/12/09

REPOSITORIES: GEO

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Project description:Healing process after connective tissues (CT) injury is complex but important as CT are critical for human moving, and patient outcome of CT injured patients is protracted with high individual variation. Specific markers which could be used for healing prognosis will be great help to monitor patient outcome, and furtherly improve target treatment and patient recovery. Although several common factors like age, gender and body mass index (BMI) were reported to predict ATR healing outcome [references], more specific markers which can be used as predictors of patient outcome after ATR are still lacking. Several biomarkers have been reported to associate with tendon healing, and indicated their relationship with patient outcome(1-4). These results highlight the potential of protein expression detection and analysis for tendon study in general and healing outcome prognosis in particular. Collagen type I (Col1a1) is the main component of Achilles tendon and plays vital role in tendon healing via involving in collagen fibrils production among tendon fibroblasts(5). Higher production of Col1a1 is associated with faster tendon repair(6), previous study on animal model reported the increased Col1a1 synthesis can exert a positive effect on tendon healing[?]. Thus, functional proteins with high impact on Col1a1 can be used not only to improve tendon healing, also can be as targets for healing improvement and outcome prediction. The proteome file of Achilles tendon which is important to increase understanding of tendon healing and help to identify accurate outcome-related biomarkers is however lagged behind. The identification of proteomic profile of Achilles tendon is very much limited in number of proteins and sample size(7-9), and is even few on human. Recent improvement in proteomic assay based on mass spectrometry (MS) made it possible to assemble the proteomic landscape of human tissues(10, 11) with high quality and sensitivity. To characterize the proteomic components in human Achilles tendon, we utilized biopsies from ATR patients with both good and poor 1-year healing outcome. A validated platform including quantitative MS and clinical database was used to identify proteomic landscape and potential bio-predictors of clinical outcome. Our study may provide a more comprehensive landscape of proteins for human Achilles tendon, as well as specific biomarkers which can be used for long term outcome prognosis after ATR.

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Rapamycin limits peritendinous fibrosis but does not affect intratendinous healing in a rodent Achilles tendon injury model

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