RESUMEN
Extracellular vesicles (EVs) have been suggested to transmit the health-promoting effects of exercise throughout the body. Yet, the mechanisms by which beneficial information is transmitted from extracellular vesicles to recipient cells are poorly understood, precluding a holistic understanding of how exercise promotes cellular and tissue health. In this study, using articular cartilage as a model, we introduced a network medicine paradigm to simulate how exercise facilitates communication between circulating EVs and chondrocytes, the cells resident in articular cartilage. Using the archived small RNA-seq data of EV before and after aerobic exercise, microRNA regulatory network analysis based on network propagation inferred that circulating EVs activated by aerobic exercise perturb chondrocyte-matrix interactions and downstream cellular aging processes. Building on the mechanistic framework identified through computational analyses, follow up experimental studies interrogated the direct influence of exercise on EV-mediated chondrocyte-matrix interactions. We found that pathogenic matrix signaling in chondrocytes was abrogated in the presence of exercise-primed EVs, restoring a more youthful phenotype, as determined by chondrocyte morphological profiling and evaluation of chondrogenicity. Epigenetic reprograming of the gene encoding the longevity protein, α-Klotho, mediated these effects. These studies provide mechanistic evidence that exercise transduces rejuvenation signals to circulating EVs, endowing EVs with the capacity to ameliorate cellular health even in the presence of an unfavorable microenvironmental signals.
RESUMEN
ABSTRACT: Physiatrists are increasingly using musculoskeletal ultrasound for both diagnostic and therapeutic purposes. However, a standardized longitudinal curriculum for instructing physical medicine and rehabilitation residents in performing ultrasound-guided interventional procedures has yet to be established. The purpose of this study is to develop and assess the effectiveness of a longitudinal curriculum in training residents to perform common ultrasound-guided musculoskeletal injections using fresh-frozen cadaveric specimens. The course included six weekly hands-on educational sessions, divided by anatomical region, integrated into an established anatomy and physical examination curriculum. After completion of the curriculum, residents reported improved comfort and confidence and displayed improved competence in performing these injections. Other physiatry residency programs should consider implementing longitudinal, hands-on cadaveric training courses to better prepare trainees to perform ultrasound-guided injections as part of their future clinical practice.
