Paraspinal Muscle Health is Related to Fibrogenic, Adipogenic, and Myogenic Gene Expression in Patients with Lumbar Spine Pathology

BACKGROUND Lumbar spine pathology is a common feature of lower back and/or lower extremity pain and is associated with observable degenerative changes in the lumbar paraspinal muscles that are associated with poor clinical prognosis. Despite the commonly observed phenotype of muscle degeneration in this patient population, its underlying molecular mechanisms are not well understood. The aim of this study was to investigate the relationships between groups of genes within the atrophic, myogenic, fibrogenic, adipogenic, and inflammatory pathways and multifidus muscle health in individuals undergoing surgery for lumbar spine pathology. METHODS Multifidus muscle biopsies were obtained from patients (n = 59) undergoing surgery for lumbar spine pathology to analyze 42 genes from relevant adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic gene pathways using quantitative polymerase chain reaction. Multifidus muscle morphology was examined preoperatively in these patients at the level and side of biopsy using T2-weighted magnetic resonance imaging to determine whole muscle compartment area, lean muscle area, fat cross-sectional areas, and proportion of fat within the muscle compartment. These measures were used to investigate the relationships between gene expression patterns and muscle size and quality. RESULTS Relationships between gene expression and imaging revealed significant associations between decreased expression of adipogenic/metabolic gene (PPARD), increased expression of fibrogenic gene (COL3A1), and lower fat fraction on MRI (r = -0.346, p = 0.018, and r = 0.386, p = 0.047 respectively). Decreased expression of myogenic gene (mTOR) was related to greater lean muscle cross-sectional area (r = 0.388, p = 0.045). CONCLUSION Fibrogenic and adipogenic/metabolic genes were related to pre-operative muscle quality, and myogenic genes were related to pre-operative muscle size. These findings provide insight into molecular pathways associated with muscle health in the presence of lumbar spine pathology, establishing a foundation for future research that addresses how these changes impact outcomes in this patient population

Paraspinal muscle gene expression across different aetiologies in individuals undergoing surgery for lumbar spine pathology

PURPOSE The purpose of this study was to understand potential baseline transcriptional expression differences in paraspinal skeletal muscle from patients with different underlying lumbar pathologies by comparing multifidus gene expression profiles across individuals with either disc herniation, facet arthropathy, or degenerative spondylolisthesis. METHODS Multifidus biopsies were obtained from patients (n = 44) undergoing lumbar surgery for either disc herniation, facet arthropathy, or degenerative spondylolisthesis. Diagnostic categories were based on magnetic resonance images, radiology reports, and intraoperative reports. Gene expression for 42 genes was analysed using qPCR. A one-way analysis of variance was performed for each gene to determine differences in expression across diagnostic groups. Corrections for multiple comparisons across genes (Benjamini-Hochberg) and for between-group post hoc comparisons (Sidak) were applied. RESULTS Adipogenic gene (ADIPOQ) expression was higher in the disc herniation group when compared to the facet arthropathy group (p = 0.032). Adipogenic gene (PPARD) expression was higher in the degenerative spondylolisthesis group when compared to the disc herniation group (p = 0.013), although absolute gene expression levels for all groups was low. Fibrogenic gene (COL3A1) had significantly higher expression in the disc herniation group and facet arthropathy group when compared to the degenerative spondylolisthesis group (p < 0.001 and p = 0.038, respectively). When adjusted for multiple comparisons, only COL3A1 remained significant (p = 0.012). CONCLUSION Individuals with disc herniation and facet arthropathy demonstrate higher COL3A1 gene expression compared to those with degenerative spondylolisthesis. Future research is required to further understand the biological relevance of these transcriptional differences

Paraspinal muscles in individuals undergoing surgery for lumbar spine pathology lack a myogenic response to an acute bout of resistance exercise

BACKGROUND: Lumbar spine pathology (LSP) is a common source of low back or leg pain, and paraspinal muscle in these patients demonstrates fatty and fibrotic infiltration, and cellular degeneration that do not reverse with exercise-based rehabilitation. However, it is unclear of this lack of response is due to insufficient exercise stimulus, or an inability to mount a growth response. The purpose of this study was to compare paraspinal muscle gene expression between individuals with LSP who do and do not undergo an acute bout of resistance exercise. METHODS: Paraspinal muscle biopsies were obtained from 64 individuals with LSP undergoing spinal surgery. Eight participants performed an acute bout of machine-based lumbar extension resistance exercise preoperatively. Gene expression for 42 genes associated with adipogenic/metabolic, atrophic, fibrogenic, inflammatory, and myogenic pathways was measured, and differential expression between exercised and non-exercised groups was evaluated for (a) the full cohort, and (b) an age, gender, acuity, and etiology matched sub-cohort. Principal components analyses were used to identify gene expression clustering across clinical phenotypes. RESULTS: The exercised cohort demonstrated upregulation of inflammatory gene IL1B, inhibition of extracellular matrix components (increased MMP3&9, decreased TIMP1&3, COL1A1) and metabolic/adipogenic genes (FABP4, PPARD, WNT10B), and downregulation of myogenic (MYOD, ANKRD2B) and atrophic (FOXO3) genes compared to the non-exercised cohort, with similar patterns in the matched sub-analysis. There were no clinical phenotypes significantly associated with gene expression profiles. CONCLUSION: An acute bout of moderate-high intensity resistance exercise did not result in upregulation of myogenic genes in individuals with LSP. The response was characterized by mixed metabolic and fibrotic gene expression, upregulation of inflammation, and downregulation of myogenesis

Comparison of lateral lumbar interbody fusion (LLIF) with open versus percutaneous screw fixation for adult degenerative scoliosis

Study designRetrospective Review.ObjectivesCompare clinical outcomes and radiographic correction of adult degenerative scoliosis (ADS) patients treated with lateral lumbar interbody fusion (LLIF), combined either with percutaneous (no laminectomy) versus open laminectomy/pedicle screw instrumentation.MethodsTwenty-two ADS patients undergoing combined LLIF and posterior instrumentation were divided into two groups: thirteen patients underwent LLIF with open laminectomy and posterior pedicle instrumentation (Group-1, six revision); nine patients underwent LLIF with percutaneous pedicle instrumentation (no decompression) (Group-2). Radiographs, CT/MRI, peri-operative complications, VAS, SF-12, and ODI were measured.ResultsAverage follow up was 22 months. In Group-1 and Group-2, respectively: Mean coronal Cobb angle corrected 12.6° and 5.8°; Mean regional lumbar lordosis improved 11.1° and 3.8°; Pelvic incidence minus lumbar lordosis mismatch corrected to within +/-9° in 46% and 0% of patients; Mean VAS improved from 5.4 to 2.8 and 6.3 to 1; Mean ODI improved 19% and 22%. Improvements were found in SF-12 PCS and MCS scores.ConclusionsBoth open and percutaneous posterior techniques following LLIF significantly improved clinical outcomes. Open procedures resulted in significantly better radiographic improvements but also higher complication rates. LLIF with percutaneous posterior fixation, without decompression, should be considered part of the algorithm in select ADS patients with remaining compensatory mechanisms and understanding that greater degrees of correction may require an open, more extensive approach

Nonoperative Management of a Severe Proximal Rectus Femoris Musculotendinous Injury in a Recreational Athlete: A Case Report.

This report describes a severe injury to the proximal rectus femoris (RF) muscle in a 37-year-old recreational athlete. This injury is a relatively rare occurrence in both the general and elite athletic populations. Acute and long-term imaging and functional outcomes are described. This athlete was able to return to full activity without surgical intervention. Follow-up imaging demonstrated gross healing of both complete (or near complete) muscle and tendon tears. LEVEL OF EVIDENCE: V

Nonoperative management of a severe proximal rectus femoris musculotendinous injury in a recreational athlete: a case report

This report describes a severe injury to the proximal rectus femoris (RF) muscle in a 37-year-old recreational athlete. This injury is a relatively rare occurrence in both the general and elite athletic populations. Acute and long-term imaging and functional outcomes are described. This athlete was able to return to full activity without surgical intervention. Follow-up imaging demonstrated gross healing of both complete (or near complete) muscle and tendon tears

Cell populations and muscle fiber morphology associated with acute and chronic muscle degeneration in lumbar spine pathology.

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

Cell populations and muscle fiber morphology associated with acute and chronic muscle degeneration in lumbar spine pathology

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