Many chronic musculoskeletal conditions are associated with loss of muscle volume and quality, resulting in functional decline. While atrophy has long been implicated as the mechanism of muscle loss in these conditions, recent evidence has emerged demonstrating a degenerative phenotype of muscle loss consisting of disrupted muscle fiber membranes, infiltration of cells into muscle fibers, and as previously describer, possible replacement of muscle fibers by adipose tissue. Here, we use human lumbar spine pathology as a model system to provide a more comprehensive analysis of the morphological features of this mode of muscle loss between early and late stages of disease, including an analysis of the cell populations found in paraspinal muscle biopsies from humans with acute vs chronic lumbar spine pathology. Using longitudinal sections, we show that degeneration of muscle fibers is localized within a fiber (ie, focal), and is characterized by discontinuous or ragged membrane disruption, cellular infiltration, and apparently vacant space containing limited numbers of nuclei and hyper-contractile cell debris. Samples from patients with acute and chronic pathology demonstrate similar magnitudes of muscle degeneration, however, larger proportions of PDGFRβ-positive progenitor cells and leukocytes were observed in the acute group, with no differences in myogenic cells, macrophages, or T-cells. By better understanding the cell population behaviors over the course of disease, therapies can be optimized to address the appropriate targets and timing of administration to minimize the functional consequences of muscle degeneration in lumbar spine pathology.

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