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: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.
Project description:Duck reovirus (DRV) is well-studied aquatic bird virus belonging to the Orthoreovirus genus of the Reoviridae family. The bursa of Fabricius is an immunologically organ against virus invasion. However, the responses of the bursa of Fabricius of Cairna moschata to DRV infection are largely unknown. To investigate the immune responses, the proteomes from the control and two DRV strain infected samples (NH and DJ) were compared. In total, 7075 protein were identified, of which 5625 protein were quantified. A number of differentially expressed proteins (DEPs), including 210 DEPs under the HN10 infection and 55 DEPs under the JD10 infection, were identified. Protein network analysis showed that the DEPs enriched in the serine protease system and the innate immune response clusters. For the serine protease systems, coagulation factor IX, three chains of fibrinogen, and complement C8, C5, and C2s were significantly up-regulated, suggesting that the serine protease-mediated immune might be involved in the responses to the HN10 infection. For the innate and adaptive immune system, RIG-I, MDA5, MAPK20, and IRF3 were significantly up-regulated, indicating their important role in the reorganization of invaded virus. Furthermore, the DEPs among different visceral organs (liver, spleen, and the bursa of Fabricius) were compared. coagulation factor IX was significantly up-regulated in the bursa of fabricius, not in the liver and spleen samples, suggesting an important role of the bursa of fabricius in antivirus. Our data may give a comprehensive resource for investigating the regulation mechanism involved in the responses of the bursa of Fabricius of duck to the DRV infections.
Project description:In the avian host, comprehensively cataloging immune cell types, their transcriptome profiles, and varying molecular responses to pathogen challenges are necessary steps toward a better understanding of the interplay between genetics and disease resilience. We present a first nuclei atlas of immune cell types derived from the three main immune organs of layer chickens, including spleen, bursa, and thymus. In bursa we also present, an accounting of cell type activation with the bacterial toxin lipopolysaccharide (LPS). Our analysis includes 36,370 total nuclei and 16, 12, and 12 transcriptionally distinct clusters for spleen, bursa, and thymus, respectively. We discover nuclei molecular profiles that uniquely distinguish states of the transcriptome within cell type that could serve as new means to characterize avian immune subtypes. We further subcluster refined immune cell type classifications, specifically highlighting the transcriptomic diversity of B and T cell subtypes. In the bursa, inferred intercellular communication and signaling pathway enrichment analyses across immune and non-immune cell types demonstrate the unappreciated complexity of the B cell repertoire in a model mimicking systemic bacterial infection. This census of all cell types in both primary and one major secondary avian immune organ system, although preliminary, provides a first review of how nuclei transcribe numerous genes, known and unknown, a critical prerequisite for the study avian immunogenetics by cell type.