Increased fibrogenic gene expression in multifidus muscles of patients with chronic versus acute lumbar spine pathology
Shahidi B, Fisch KM, Gibbons MC, Ward SR.
Spine, 2020 45(4):E189-E195.
Spine, 2020 45(4):E189-E195.
Abstract:
STUDY DESIGN: Prospective observational study-basic science (Level 1).
OBJECTIVE: The aim of this study was to compare expression of functional groups of genes within the atrophic, myogenic, fibrogenic, adipogenic, and inflammatory pathways between paraspinal muscle biopsies from individuals with acute and chronic lumbar spine pathology.
SUMMARY OF BACKGROUND DATA: Low back pain is a complex and multifactorial condition that affects a majority of the general population annually. Changes in muscle tissue composition (i.e., fatty and fibrotic infiltration) are a common feature in individuals with lumbar spine pathology associated with low back pain, which often results in functional loss. Understanding the molecular underpinnings of these degenerative changes in different phases of disease progression may improve disease prevention and treatment specificity.
METHODS: Intraoperative biopsies of the multifidus muscle were obtained from individuals undergoing surgery for acute (<6-month duration) or chronic (>6-month duration) lumbar spine pathology. Expression of 42 genes related to myogenesis, atrophy, adipogenesis, metabolism, inflammation, and fibrosis were measured in 33 samples (eight acute, 25 chronic) using qPCR, and tissue composition of fat, muscle, and fibrosis was quantified using histology.
RESULTS: We found that tissue composition of the biopsies was heterogeneous, resulting in a trend toward lower RNA yields in biopsies with higher proportions of fat (r <-0.39, P < 0.1). There were no significant differences in gene expression patterns for atrophy (P > 0.635), adipogenesis (P > 0.317), myogenesis (P > 0.320), or inflammatory (P > 0.413) genes after adjusting for the proportion of muscle, fat, and connective tissue. However, in the fibrogenesis pathway, we found significant upregulation of CTGF (P = 0.046), and trends for upregulation of COL1A1 (P = 0.061), and downregulation of MMP1 and MMP9 (P = 0.061) in the chronic group.
CONCLUSION: There is increased fibrogenic gene expression in individuals with chronic disease when compared to acute disease, without significant differences in atrophic, myogenic, adipogenic, or inflammatory pathways, suggesting increased efforts should be made to prevent or reverse fibrogenesis to improve patient function in this population.
LEVEL OF EVIDENCE: N/A.
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METHODS: Intraoperative biopsies of the multifidus muscle were obtained from individuals undergoing surgery for acute (<6-month duration) or chronic (>6-month duration) lumbar spine pathology. Expression of 42 genes related to myogenesis, atrophy, adipogenesis, metabolism, inflammation, and fibrosis were measured in 33 samples (eight acute, 25 chronic) using qPCR, and tissue composition of fat, muscle, and fibrosis was quantified using histology.
RESULTS: We found that tissue composition of the biopsies was heterogeneous, resulting in a trend toward lower RNA yields in biopsies with higher proportions of fat (r <-0.39, P < 0.1). There were no significant differences in gene expression patterns for atrophy (P > 0.635), adipogenesis (P > 0.317), myogenesis (P > 0.320), or inflammatory (P > 0.413) genes after adjusting for the proportion of muscle, fat, and connective tissue. However, in the fibrogenesis pathway, we found significant upregulation of CTGF (P = 0.046), and trends for upregulation of COL1A1 (P = 0.061), and downregulation of MMP1 and MMP9 (P = 0.061) in the chronic group.
CONCLUSION: There is increased fibrogenic gene expression in individuals with chronic disease when compared to acute disease, without significant differences in atrophic, myogenic, adipogenic, or inflammatory pathways, suggesting increased efforts should be made to prevent or reverse fibrogenesis to improve patient function in this population.
LEVEL OF EVIDENCE: N/A.
Full text (pdf)