Shahidi Bahar, Gibbons Michael C, Esparza Mary, Zlomislic Vinko, Allen Richard Todd, Garfin Steven R, Ward Samuel R
Department of Orthopaedic Surgery University of California San Diego San Diego California USA.
Department of Bioengineering University of California San Diego San Diego California USA.
JOR Spine. 2020 Apr 8;3(2):e1087. doi: 10.1002/jsp2.1087. eCollection 2020 Jun.
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.
许多慢性肌肉骨骼疾病与肌肉体积和质量的丧失有关，导致功能下降。虽然长期以来萎缩一直被认为是这些疾病中肌肉丧失的机制，但最近有证据表明，肌肉丧失存在一种退行性表型，包括肌纤维膜破裂、细胞浸润到肌纤维中，以及如前所述的脂肪组织可能替代肌纤维。在这里，我们以人类腰椎病理学作为模型系统，对疾病早期和晚期这种肌肉丧失模式的形态学特征进行更全面的分析，包括对患有急性与慢性腰椎病理学的人类椎旁肌活检中发现的细胞群体进行分析。使用纵切面，我们显示肌纤维的退化局限在一根纤维内（即局灶性），其特征为膜的不连续或参差不齐的破裂、细胞浸润，以及明显有空虚空间，其中含有数量有限的细胞核和过度收缩的细胞碎片。急性和慢性病理学患者的样本显示出相似程度的肌肉退化，然而，在急性组中观察到更大比例的血小板衍生生长因子受体β（PDGFRβ）阳性祖细胞和白细胞，而生肌细胞、巨噬细胞或T细胞没有差异。通过更好地了解疾病过程中的细胞群体行为，可以优化治疗方法，以针对合适的靶点和给药时机，将腰椎病理学中肌肉退化的功能后果降至最低。
