mRNA expressions of peroxisome proliferator-activated receptor gamma coactivator 1α, tumor necrosis factor-α, and interleukin-6 in paraspinal muscles of patients with lumbar kyphosis: a preliminary study

Abstract

BackgroundKyphosis is a spine deformity that can lead to falls and reduced quality of life. Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) regulates mitochondrial biogenesis and is important for proper functioning of skeletal muscle, including the paraspinal muscles, which support and allow movement of the spine. The role of PGC-1α in paraspinal muscles in lumbar kyphosis has not been examined. We also examined the expressions of the proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-6.MethodsWe obtained paraspinal muscle specimens from 12 patients who underwent posterior lumbar surgery. RNA was isolated from these samples, and quantitative PCR was performed to compare the expression levels of PGC-1α, TNF-α, and IL-6 mRNA between patients with decreased lumbar lordosis (LL) and normal LL patients.ResultsTNF-α and IL-6 mRNA expressions in paraspinal muscles were significantly higher in the decreased LL group than in the normal LL group (P=0.048 for both). PGC-1α mRNA expression was slightly increased in the decreased LL group, but the difference was not significant. Age was significantly positively correlated with PGC-1α mRNA expression (P=0.010). PGC-1α mRNA expression was significantly positively correlated with TNF-α mRNA expression (P=0.022). LL was significantly negatively correlated with PGC-1α, TNF-α, and IL-6 mRNA expressions (P=0.015, 0.036, and 0.010, respectively).ConclusionTNF-α and IL-6 mRNA expressions in paraspinal muscles were significantly higher in the decreased LL group than in the normal LL group. LL was significantly negatively correlated with PGC-1α, TNF-α, and IL-6 mRNA expressions. PGC-1α mRNA expression levels in paraspinal muscles may be affected by lumbar kyphosis.

Paraspinal muscle pathophysiology associated with low back pain and spine degenerative disorders

“…Equally few articles have studied the effects of spine pathology on the gene expression of the paraspinal muscles 38,40–42 . Kudo et al 38 discovered that genes associated with impaired muscle function (PGC‐1α) as well as proinflammatory genes (tumor necrosis factor (TNF)‐α and interleukin (IL)‐6) were greater in multifidus samples from patients undergoing posterior lumbar spinal surgery who had a reduced lumbar lordosis (ie., lumbar kyphosis) when compared to patients with normal lumbar lordosis.…”

“…The paraspinal muscles of patients with LBPDs are prone to developing fatty infiltration (intrusion of fatty tissue into the body of the muscle), fibrosis (tissue remodeling whereby normal tissue is replaced by collagen‐based connective tissue), and possibly atrophy (the loss of contractile protein volume, ie, reduced cross‐sectional area of muscle cells and whole muscle); all of which can be considered features of muscle degeneration. For example, fatty and/or fibrotic changes have been regularly observed using noninvasive imaging in IVD herniation (eg, References 12 , 38 , 74 ), facet joint osteoarthritis (eg, Reference 75 ), nonspecific low back pain (eg, References 13 , 76 , 77 , 78 , 79 ), and spinal stenosis, 80 including greater fatty/fibrotic infiltration in patients who have a lower compared to higher functional status (eg, References 80 , 81 ). Interestingly, a statistically significant difference in multifidus fat content between CLBP and asymptomatic volunteers was only found in the intramyocellular (0.61 ± 0.27 (×10 3 ) mmol L −1 vs 0.26 ± 0.14 (×10 3 ) mmol L −1 , respectively) rather than extramyocellular (2.63 ± 1.75 (×10 3 ) mmol L −1 vs 1.52 ± 1.54 (×10 3 ) mmol L −1 , respectively) stores, 78 and a statistically significant correlation between multifidus fat content and visual analog scale (VAS) for pain in CLBP patients was again only found intracellularly and not extracellularly, 79 both in studies using MR spectroscopy.…”

“…Equally few articles have studied the effects of spine pathology on the gene expression of the paraspinal muscles. 38 , 40 , 41 , 42 Kudo et al 38 discovered that genes associated with impaired muscle function (PGC‐1α) as well as proinflammatory genes (tumor necrosis factor (TNF)‐α and interleukin (IL)‐6) were greater in multifidus samples from patients undergoing posterior lumbar spinal surgery who had a reduced lumbar lordosis (ie., lumbar kyphosis) when compared to patients with normal lumbar lordosis. Likewise, greater expression of pro‐inflammatory and lower expression of anti‐inflammatory genes have been found in the multifidus as well as adipose (intramuscular and subcutaneous) tissue of patients with high vs low muscle fatty infiltration (Kjaer grade).…”

“…Numerous spine pathologies, including intervertebral disc (IVD) herniation, 17,18 sagittal balance disorder, 19–22 and nonspecific low back pain 12,23–25 are associated with paraspinal muscle adaptations; therefore, these muscle adaptations have been linked with a lowered quality of life for millions of patients annually 26–28 . Frequently reported muscle‐specific adaptations to spine pathology and low back pain include: lower muscle endurance 11,29,30 and lower muscle strength, 10,11,31 muscle atrophy, 17,23,24 fiber type changes, 26,32,33 increased intramuscular fat 24,34 and connective tissue, 18,35,36 distorted cell populations, 18,37 and altered gene expression 38–41 . It should be noted that reported findings from some of these studies are unable to compare to true controls (ie, asymptomatic patients) due to the invasive nature of paraspinal muscle biopsies required to make certain measurements; the details of these comparisons will be discussed throughout the main section of the text.…”

“… 26 , 27 , 28 Frequently reported muscle‐specific adaptations to spine pathology and low back pain include: lower muscle endurance 11 , 29 , 30 and lower muscle strength, 10 , 11 , 31 muscle atrophy, 17 , 23 , 24 fiber type changes, 26 , 32 , 33 increased intramuscular fat 24 , 34 and connective tissue, 18 , 35 , 36 distorted cell populations, 18 , 37 and altered gene expression. 38 , 39 , 40 , 41 It should be noted that reported findings from some of these studies are unable to compare to true controls (ie, asymptomatic patients) due to the invasive nature of paraspinal muscle biopsies required to make certain measurements; the details of these comparisons will be discussed throughout the main section of the text.…”