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Intervertebral disc herniation effects on multifidus muscle composition and resident stem cell populations.

ABSTRACT: Background:Paraspinal muscles are crucial for vertebral stabilization and movement. These muscles are prone to develop fatty infiltration (FI), fibrosis, and atrophy in many spine conditions. Fibro-adipogenic progenitors (FAPs), a resident muscle stem cell population, are the main contributors of muscle fibrosis and FI. FAPs are involved in a complex interplay with satellite cells (SCs), the primary myogenic progenitor cells within muscle. Little is known about the stem cell composition of the multifidus. The aim of this study is to examine FAPs and SCs in the multifidus in disc herniation patients. Multifidus muscle samples were collected from 10 patients undergoing decompressive spine surgery for lumbar disc herniation. Hamstring muscle was collected from four patients undergoing hamstring autograft ACL reconstruction as an appendicular control. Multifidus tissue was analyzed for FI and fibrosis using Oil-Red-O and Masson's trichrome staining. FAPs and SCs were visualized using immunostaining and quantified with fluorescence-activated cell sorting (FACS) sorting. Gene expression of these cells from the multifidus were analyzed with reverse transcription-polymerase chain reaction and compared to those from hamstring muscle. FI and fibrosis accounted for 14.2%± 7.4% and 14.8%±4.2% of multifidus muscle, respectively. The multifidus contained more FAPs (11.7%±1.9% vs 1.4%±0.2%; P<.001) and more SCs (3.4%±1.6% vs 0.08%±0.02%; P=.002) than the hamstring. FAPs had greater ? Smooth Muscle Actin (?SMA) and adipogenic gene expression than FAPs from the hamstring. SCs from the multifidus displayed upregulated expression of stem, proliferation, and differentiation genes. Conclusion:The multifidus in patients with disc herniation contains large percentages of FAPs and SCs with different gene expression profiles compared to those in the hamstring. These results may help explain the tendency for the multifidus to atrophy and form FI and fibrosis as well as elucidate potential approaches for mitigating these degenerative changes by leveraging these muscle stem cell populations.

SUBMITTER: Agha O

PROVIDER: S-EPMC7323461 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Intervertebral disc herniation effects on multifidus muscle composition and resident stem cell populations.

Agha Obiajulu O Mueller-Immergluck Andreas A Liu Mengyao M Zhang He H Theologis Alekos A AA Clark Aaron A Kim Hubert T HT Liu Xuhui X Feeley Brian T BT Bailey Jeannie F JF

JOR spine 20200506 2

<h4>Background</h4>Paraspinal muscles are crucial for vertebral stabilization and movement. These muscles are prone to develop fatty infiltration (FI), fibrosis, and atrophy in many spine conditions. Fibro-adipogenic progenitors (FAPs), a resident muscle stem cell population, are the main contributors of muscle fibrosis and FI. FAPs are involved in a complex interplay with satellite cells (SCs), the primary myogenic progenitor cells within muscle. Little is known about the stem cell composition ...[more]

PMID: 32613166

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Project description:Intervertebral disc herniation (IVDH) is an important pathology in humans and also in dogs. While the molecular disease mechanisms are well investigated in humans, little is known about the inflammatory mediators in naturally occurring canine IVDH. The objective of this study was to investigate whether the involved proinflammatory cytokines in human IVDH are also key cytokines in canine IVDH and thus to elucidate the suitability of the dog as a model for human trials. 59 samples from 25 dogs with surgically confirmed thoracolumbar IVDH were collected and classified in three subgroups: herniated (H), affected non-herniated (NH) disc, and adjacent non-affected (NA) disc. Discs from 11 healthy dogs acted as controls (C). Samples were analyzed for IL-1, IL-6, IL-8, and TNF-? expression (qPCR/ELISA) as well as cell infiltration and activation of the MAP kinase pathways (immunohistochemistry). Gene and protein expression of all key cytokines could be detected in IVDH affected dogs. Canine IVDH was significantly associated with a higher gene expression of IL-6 (H?>?C, NH?>?C) and TNF-? (H?>?C, NH?>?C, NA?>?C) and a significant down-regulation of IL-1? (H?<?C). Dogs with spontaneous pain had significantly higher IL-6 mRNA compared to those with pain arising only upon palpation. An inter-donor comparison (H and HN relative to NA) revealed a significant increase of IL-6 gene expression (H?>?NA, NH?>?NA). IL-8 (H?>?C, NA?>?C) and TNF-? (NH?>?C) protein levels were significantly increased in diseased dogs while inversely, IL-6 protein levels were significantly higher in patients with better clinical outcome. Aside from resident IVD cells, mostly monocytes and macrophages were found in extruded material, with concomitant activation of extracellular signal-regulated kinase p38 in the majority of samples. Dogs with spontaneous IVDH might provide a useful model for human disc diseases. Although the expression of key cytokines found in human IVDH was also demonstrated in canine tissue, the inflammatory mechanisms accompanying canine IVDH diverges partially from humans, which will require further investigations in the future. In dogs, IL-6 seems to play an important pathological role and may represent a new potential therapeutic target for canine patients.

Project description:ObjectiveTo investigate the effect of protrusion amount on pain, lumbar mobility, physical dysfunction, and the cross-sectional area of the multifidus muscle in patients with lumbar disc herniation.Methods54 male patients aged 20 to 50 years were included in this study in 2 groups. The control group (n = 18) consisted of patients with disc herniation without nerve root compression, and the study group (n = 36) consisted of patients with lumbar disc herniation and nerve root compression in 3 subgroups according to the amount of protrusion. The multifidus muscle cross-sectional area and the amount of protrusion were measured using Magnetic Resonance Imaging. Pain intensity was measured using the Visual Pain Scale, physical dysfunction was measured using the Oswestry Disability Index, flexion-extension was measured with TiltMeter, and trunk rotation was measured with smartphone applications called iPhone Compass.ResultsThere were no differences in pain levels (P > .05), mean trunk rotation movements of the affected and unaffected sides (P = .001, P = .001, P = .983, and P = .954, respectively), Oswestry Disability Index results (P = .967), or cross-sectional area sizes of the multifidus muscle (P = .866, P = .552, P = .787, respectively). There was a difference between the groups in terms of the mean trunk flexion and extension movement values (P = .001). The regression analysis indicated that there was no significant correlation between the binary variables, and the models exhibited a low explanatory rate for the dependent variable.ConclusionA relationship has been identified between lumbar disc herniation and low back pain, lumbar movement limitation, and physical functionality. Nevertheless, subsequent to the regression analysis, it became evident that the binary variables did not exhibit a noteworthy relationship, leading to a decrease in the explanatory capacity of the models for the dependent variable. In forthcoming studies, it is advisable to contemplate the augmentation of the subject pool or the incorporation of multiple independent variables into the regression analysis as potential strategies to enhance the model capability in elucidating variations in the dependent variable.

Project description:Lumbar intervertebral disc herniation, as a leading cause of low back pain, productivity loss, and disability, is a common musculoskeletal disorder that results in significant socioeconomic burdens. Despite extensive clinical and basic scientific research efforts, herniation etiopathogenesis, particularly its initiation and progression, is not well understood. Understanding herniation etiopathogenesis is essential for developing effective preventive measures and therapeutic interventions. Thus, this review seeks to provide a thorough overview of the advances in herniation-oriented research, with a discussion on ongoing challenges and potential future directions for clinical, translational, and basic scientific investigations to facilitate innovative interdisciplinary research aimed at understanding herniation etiopathogenesis. Specifically, risk factors for herniation are identified and summarized, including familial predisposition, obesity, diabetes mellitus, smoking tobacco, selected cardiovascular diseases, disc degeneration, and occupational risks. Basic scientific experimental and computational research that aims to understand the link between excessive mechanical load, catabolic tissue remodeling due to inflammation or insufficient nutrient supply, and herniation, are also reviewed. Potential future directions to address the current challenges in herniation-oriented research are explored by combining known progressive development in existing research techniques with ongoing technological advances. More research on the relationship between occupational risk factors and herniation, as well as the relationship between degeneration and herniation, is needed to develop preventive measures for working-age individuals. Notably, researchers should explore using or modifying existing degeneration animal models to study herniation etiopathogenesis, as such models may allow for a better understanding of how to prevent mild-to-moderately degenerated discs from herniating.

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Intervertebral disc herniation effects on multifidus muscle composition and resident stem cell populations.

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Intervertebral disc herniation effects on multifidus muscle composition and resident stem cell populations.

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