Can Proinflammatory Cytokine Gene Expression Explain Multifidus Muscle Fiber Changes After an Intervertebral Disc Lesion?

Hodges, Paul W.; James, Gregory; Blomster, Linda V.; Hall, Leanne; Schmid, Annina B.; Shu, Cindy; Little, Christopher B.; Melrose, James

doi:10.1097/brs.0000000000000318

Cited by 63 publications

(135 citation statements)

References 59 publications

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“…19 Muscle harvested at 6 months was used in earlier analyses. 6 Procedures were approved by the University of Sydney animal care and ethics care committee.…”

Section: Animalsmentioning

confidence: 99%

“…Surgical procedures for remaining animals were performed as previously described. 6 In brief, 17 animals were anesthetized and received lesions (20-mm wide × 6-mm deep to penetrate annulus fi brosis without entering nucleus pulpous) to the left annular IVD at L1-L2, L3-L4, and L5-L6 via an extraperitoneal approach. Animals were held in pens for 10 days to monitor wound healing and lameness.…”

Section: Surgical Procedure Ivd Lesion and Postoperative Carementioning

confidence: 99%

“…6 In brief, muscle cells were identifi ed as fast or slow on the basis of reaction to specifi c antibodies (mouse antislow and -fast Myosin [Sigma, St. Louis, Mo]), and intermediate if they reacted to both 20 ( Figure 2 ). Muscle fi ber CSA was measured using ImageJ from a random selection of 5 to 10 muscle fi bers of each type from twelve 620 × 400-μ m images (20 × magnifi cation) (60-120 fi bers/type/animal/side).…”

Section: Muscle Fiber Analysismentioning

confidence: 99%

“…At 6 months after IVD lesion in sheep, multifi dus muscle undergoes transformation from slow-(fatigueresistant postural function 18 ) to fast-(fatigue-sensitive/high torque) muscle fi bers in conjunction with increased proinfl ammatory cytokine gene expression (tumor necrosis factor [TNF]-α /interleukin [IL]-1 β ). 6 Key issues to resolve are the molecular link between cytokines and structural changes (muscle and noncontractile) and their time course.…”

mentioning

confidence: 99%

“…6 This creates a platform for detailed cellular analysis. Figure 1 presents putative mechanisms for multifi dus changes, including signaling pathways for muscle atrophy, adipogenesis, and muscle fi brosis.…”

mentioning

confidence: 99%

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Multifidus Muscle Changes After Back Injury Are Characterized by Structural Remodeling of Muscle, Adipose and Connective Tissue, but Not Muscle Atrophy

Hodges

James

Blomster

et al. 2015

Spine

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124

173

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“…19 Muscle harvested at 6 months was used in earlier analyses. 6 Procedures were approved by the University of Sydney animal care and ethics care committee.…”

Section: Animalsmentioning

confidence: 99%

Section: Surgical Procedure Ivd Lesion and Postoperative Carementioning

confidence: 99%

Section: Muscle Fiber Analysismentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Multifidus Muscle Changes After Back Injury Are Characterized by Structural Remodeling of Muscle, Adipose and Connective Tissue, but Not Muscle Atrophy

Hodges

James

Blomster

et al. 2015

Spine

Self Cite

124

173

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Lumbar multifidus muscle degenerates in individuals with chronic degenerative lumbar spine pathology

Shahidi

Hubbard

Gibbons

et al. 2017

Journal Orthopaedic Research

104

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Histological and cell-level changes in the lumbar musculature in individuals with chronic lumbar spine degenerative conditions are not well characterized. Although prior literature supports evidence of changes in fiber type and size, little information exists describing the tissue quality and biology of pathological features of muscle in this population. The purpose of this study was to quantify multifidus tissue composition and structure, inflammation, vascularity, and degeneration in individuals with chronic degenerative lumbar spine pathology. Human multifidus biopsies were acquired from 22 consecutive patients undergoing surgery for chronic degenerative lumbar spine pathology. Relative fractions of muscle, adipose, and extracellular matrix were quantified along with muscle fiber type and cross-sectional area (CSA) and markers of inflammation, vascularity, satellite cell density, and muscle degeneration. On average, multifidus biopsies contained 48.5% muscle, 11.7% adipose tissue, and 26.1% collagen tissue. Elevated inflammatory cell counts (48.5 ± 30.0 macrophages/mm2) and decreased vascularity (275.6 ± 69.4 vessels/mm2) were also observed compared to normative values. Satellite cell densities were on average 13 ± 9 cells per every 100 muscle fibers. Large fiber CSA (3,996.0 ± 1,909.2 um2) and a predominance of type I fibers (61.8 ± 18.0%) were observed in addition to evidence of pathological degeneration-regeneration cycling (18.8 ± 9.4% centrally nucleated fibers, and 55.2 ± 24.2% of muscle regions containing degeneration). High levels of muscle degeneration, inflammation, and decreased vascularity were commonly seen in human multifidus biopsies of individuals with lumbar spine pathology in comparison to normative data. Evidence of active muscle degeneration suggests that changes in muscle tissue are more complex than simple atrophy.

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Efficacy of administered mesenchymal stem cells in the initiation and co‐ordination of repair processes by resident disc cells in an ovine (Ovis aries) large destabilizing lesion model of experimental disc degeneration

et al. 2018

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Background Forty percent of low back pain cases are due to intervertebral disc degeneration (IVDD), with mesenchymal stem cells (MSCs) a reported treatment. We utilized an ovine IVDD model and intradiscal heterologous MSCs to determine therapeutic efficacy at different stages of IVDD. Methodology Three nonoperated control (NOC) sheep were used for MSC isolation. In 36 sheep, 6 × 20 mm annular lesions were made at three spinal levels using customized blades/scalpel handles, and IVDD was allowed to develop for 4 weeks in the Early (EA) and late Acute (LA) groups, or 12 weeks in the chronic (EST) group. Lesion IVDs received injections of 10 × 10 6 MSCs or PBS, and after 8 (EA), 22 (LA) or 14 (EST) weeks recuperation the sheep were sacrificed. Longitudinal lateral radiographs were used to determine disc heights. IVD glycosaminoglycan (GAG) and hydroxyproline contents were quantified using established methods. An Instron materials testing machine and customized jigs analyzed IVD (range of motion, neutral zone [NZ] and stiffness) in flexion/extension, lateral bending and axial rotation. qRTPCR gene profiles of key anabolic and catabolic matrix molecules were undertaken. Toluidine blue and hematoxylin and eosin stained IVD sections were histopathologically scoring by two blinded observers. Results IVDD significantly reduced disc heights. MSC treatment restored 95% to 100% of disc height, maximally improved NZ and stiffness in flexion/extension and lateral bending in the EST group, restoring GAG levels. With IVDD qRTPCR demonstrated elevated catabolic gene expression ( MMP2/3/9/13, ADAMTS4/5 ) in the PBS IVDs and expession normalization in MSC‐treated IVDs. Histopathology degeneracy scores were close to levels of NOC IVDs in MSC IVDs but IVDD developed in PBS injected IVDs. Discussion Administered MSCs produced recovery in degenerate IVDs, restored disc height, composition, biomechanical properties, down regulated MMPs and fibrosis, strongly supporting the efficacy of MSCs for disc repair.

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Can Proinflammatory Cytokine Gene Expression Explain Multifidus Muscle Fiber Changes After an Intervertebral Disc Lesion?

Abstract: N/A.

Cited by 63 publications

References 59 publications

Multifidus Muscle Changes After Back Injury Are Characterized by Structural Remodeling of Muscle, Adipose and Connective Tissue, but Not Muscle Atrophy

Multifidus Muscle Changes After Back Injury Are Characterized by Structural Remodeling of Muscle, Adipose and Connective Tissue, but Not Muscle Atrophy

Lumbar multifidus muscle degenerates in individuals with chronic degenerative lumbar spine pathology

Efficacy of administered mesenchymal stem cells in the initiation and co‐ordination of repair processes by resident disc cells in an ovine (Ovis aries) large destabilizing lesion model of experimental disc degeneration

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