Proteome analysis reveals paraspinal muscle fiber type changes in patients with degenerative lumbar scoliosis.

Abstract

Degenerative lumbar scoliosis (DLS) is a common aging-related spinal deformity. Paraspinal muscle degeneration is highly correlated with the rapid progression of DLS. However, understanding of the role of the praspinal muscle degeneration is limited because of a lack of histologic and molecular evidence. Our study profiled the proteomic alteration of paraspinal muscles and investigated the muscle fiber type transition that occurs in DLS, along with its correlation with clinical parameters. Cross-sectional basic science study using clinical data and biological samples. Paraspinal muscle samples were collected intraoperatively from the concave and convex sides of the apex vertrebrae in patients with DLS (n=10) and either side of L3 level from age- and sex-matched participants without DLS (n=10). Analysis was perfomed using isobaric tagging for relative and absolute quantitation (iTRAQ) and liquid chromatography with tandem mass spectrometry on muscle tissue from the convex side of spines in patients with DLS and in participants without DLS to identify differentially expressed proteins (DEPs). Western blotting was used to validate the DEPs. The measurement of acidity/basicity of ATPase (pH=9.4), succinic acid dehydrogenase staining, and real-time quantitative polymerase chain reaction were performed to assess the muscle fiber type change in DLS. The Pearson correlation coefficient was used to analyze the correlation between the myofiber transition and the Cobb angle of the main curve. This study was supported by the National Natural Science Foundation of China (NSFC) (No. 82272545), $ 8000-10,000 and the Jiangsu Provincial Key Medical Center, and the China Postdoctoral Science Foundation (2021M701677, $ 5000-7000). We identified 62 DEPs, of which 16 were downregulated and 46 were upregulated. Gene ontology indicated significant changes in biological processes including muscle contraction. Protein-protein interaction network analysis showed that structural muscle proteins such as MYH1 (myosin heavy chain 1) and TNNT3 (troponin T) were the key nodes. Western blotting further validated the downregulation of MYH1 in the paraspinal muscle of DLS. Histologically, ATPase staining showed a significant reduction of type II muscle fibers in DLS, consistent with the functional changes of the DEPs. Furthermore, we found that the reduction of type II muscle fibers percentage was correlated with the severity of DLS. This study is the first to elucidate the underlying molecular basis and pathways that implicate the paraspinal muscle fiber type transition in DLS. Type II myofiber percentage was diminished both on the concave side and the convex side of the paraspinal muscles in DLS, especially on the convex side, which may play an important role in the onset and/or progression of the disease. This study shows a potential molecular basis for histopathologic change in the paraspinal muscles of DLS and provides a potential tool for assessing paraspinal muscle quality and predicting the poor prognosis of DLS.