Spatial Transcriptomics Identifies Muscle Inflammation Susceptibility as a Distinct Periarticular Skeletal Muscle Phenotype in End-Stage Knee Osteoarthritis
Skeletal muscle dysfunction is a major contributor to disability and incomplete functional recovery in patients with end-stage knee osteoarthritis (KOA), yet the spatial components of disease-associated molecular remodeling remain poorly understood. Here, we applied spatial transcriptomics to paired skeletal muscle biopsies obtained from the surgical (Sx) and contralateral (Ct) limbs of…
Spatial transcriptomics has unveiled a unique muscle inflammation susceptibility (MuIS) phenotype in periarticular skeletal muscle during end-stage knee osteoarthritis (KOA). This groundbreaking study applied spatial transcriptomics to skeletal muscle biopsies from patients undergoing total knee arthroplasty (TKA). By analyzing 27,087 spots across 22 muscle histological cross-sections from 11 paired limbs, researchers identified seven spatially resolved transcriptional domains.
These domains encompassed slow and fast myofiber states, an extracellular matrix/fibroadipogenic-enriched area, a pericyte/smooth muscle domain, and a satellite cell/myogenic-enriched domain. Notably, despite advanced unilateral disease, KOA-associated remodeling primarily manifested as within-cluster transcriptional changes in fibroadipogenic, pericyte/smooth muscle, and satellite/myogenic domains.
MuIS was found to induce a coordinated transcriptional program comprising denervation- and regeneration-associated genes, along with altered contractile and metabolic features. This study marks the first spatial transcriptomic analysis of periarticular skeletal muscle in end-stage KOA, providing valuable insights into the distinct local transcriptional phenotype of MuIS in diseased muscle.
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