Project description:Tendon degeneration and injury often result in significant pain and functional impairment. Typically, tendon healing occurs through a scar-mediated response and may progress to chronic tendinopathy without timely intervention. However, the molecular mechanisms underlying early tendon repair remain poorly understood. Further investigation is also impeded by the limited availability of early tendon injury samples in clinical settings. In this study, we established a puncture-induced tendon injury model to investigate the molecular patterns and cellular subpopulations involved in early tendon injury across multiple time points. RNA sequencing identified seven gene sets with distinct expression profiles during the early stages of tendon injury. Single-cell RNA sequencing further revealed eight myeloid cell types and seven mesenchymal cell types participating in the tendon repair process. Together, these findings illuminate the molecular and cellular dynamics coordinating early tendon repair, providing insights that could inform future clinical treatments for tendinopathy and tendon injury.
Project description:Tendon degeneration and injury often result in significant pain and functional impairment. Typically, tendon healing occurs through a scar-mediated response and may progress to chronic tendinopathy without timely intervention. However, the molecular mechanisms underlying early tendon repair remain poorly understood. Further investigation is also impeded by the limited availability of early tendon injury samples in clinical settings. In this study, we established a puncture-induced tendon injury model to investigate the molecular patterns and cellular subpopulations involved in early tendon injury across multiple time points. RNA sequencing identified seven gene sets with distinct expression profiles during the early stages of tendon injury. Single-cell RNA sequencing further revealed eight myeloid cell types and seven mesenchymal cell types participating in the tendon repair process. Together, these findings illuminate the molecular and cellular dynamics coordinating early tendon repair, providing insights that could inform future clinical treatments for tendinopathy and tendon injury.
Project description:Rotator cuff injuries result in over 500,000 surgeries performed annually, an alarmingly high number of which fail. These procedures typically involve repair of the injured tendon and removal of the subacromial bursa. However, recent identification of a resident population of mesenchymal stem cells and inflammatory responsiveness of the bursa to tendinopathy indicate an unexplored biological role of the bursa in the context of rotator cuff disease. Therefore, we aimed to understand the clinical relevance of bursa-tendon crosstalk, characterize the biologic role of the bursa within the shoulder, and test the therapeutic potential for targeting the bursa. Proteomic profiling of patient bursa and tendon samples demonstrated that the bursa is activated by tendon injury. Using a rat to model rotator cuff injury and repair, tenotomy-activated bursa protected the intact tendon adjacent to the injured tendon and maintained the morphology of the underlying bone. The bursa also promoted an early inflammatory response in the injured tendon, initiating key players in wound healing. In vivo results were supported by targeted organ culture studies of the bursa. To examine the potential to therapeutically target the bursa, dexamethasone was delivered to the bursa, prompting a shift in cellular signaling towards modulating inflammation in the healing tendon. In conclusion, contrary to current clinical practice, the bursa should be retained to the greatest extent possible and provides a new therapeutically target for improving tendon healing outcomes.
Project description:To investigate the mechanism of electrical stimulation in the repair of spinal cord injury, we established a rat model of spinal cord injury. Then, we used RNA-SEQ data obtained from ES treatment and 6 different rat models of spinal cord injury for gene expression profile analysis.
Project description:Intralesional mesenchymal stem cell (MSC) therapy has improved tissue architecture and reinjury rates in equine tendon injury; however, the mechanisms by which they promote repair are still being investigated. Therefore, the objectives of this study were to determine how the predominate pro-inflammatory cytokines present in a surgically induced model of equine tendon injury modulate MSC gene and protein expression.
Project description: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.
Project description:Little is understood about the roles of tendon cells during flexor tendon healing. To better understand tendon cell functions, the Scx-Cre mouse was crossed to the DTR mouse model to facilitate scleraxis lineage cell depletion prior to acute flexor tendon injury and repair. WT (cre-) and experimental (cre+) mice underwent complete transection and repair of the flexor digitorum longus tendon. Repaired tendons were harvested at 14 and 28 days post-repair for bulk RNA-Seq analysis to examine possible mechanisms driving differential healing due to Scx lineage cell depletion.