Inflammatory biomarkers of low back pain and disc degeneration: a review

Khan, Aysha N.; Jacobsen, Hayley E.; Khan, Jansher; Filippi, Christopher G.; Levine, Mitchell; Lehman, Ronald A.; Riew, K. Daniel; Lenke, Lawrence G.; Chahine, Nadeen O.

doi:10.1111/nyas.13551

Cited by 272 publications

(243 citation statements)

References 86 publications

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“…). Multiple studies have identified immune cells after IVD injury and degeneration, including macrophages, T lymphocytes, and mast cells (Table ), as well as important proinflammatory cytokine responses . While some studies demonstrate a weak immune response in herniated tissue and with induced AF injury in animal models, repeated injury is known to increase that proinflammatory condition .…”

Section: Cellular Responses To Injurymentioning

confidence: 99%

Annulus fibrosus cell phenotypes in homeostasis and injury: implications for regenerative strategies

Torre

Mroz

Bartelstein

et al. 2018

Annals of the New York Academy of Sciences

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Despite considerable efforts to develop cellular, molecular, and structural repair strategies and restore intervertebral disk function after injury, the basic biology underlying intervertebral disk healing remains poorly understood. Remarkably, little is known about the origins of cell populations residing within the annulus fibrosus, or their phenotypes, heterogeneity, and roles during healing. This review focuses on recent literature highlighting the intrinsic and extrinsic cell types of the annulus fibrosus in the context of the injury and healing environment. Spatial, morphological, functional, and transcriptional signatures of annulus fibrosus cells are reviewed, including inner and outer annulus fibrosus cells, which we propose to be referred to as annulocytes. The annulus also contains peripheral cells, interlamellar cells, and potential resident stem/progenitor cells, as well as macrophages, T lymphocytes, and mast cells following injury. Phases of annulus fibrosus healing include inflammation and recruitment of immune cells, cell proliferation, granulation tissue formation, and matrix remodeling. However, annulus fibrosus healing commonly involves limited remodeling, with granulation tissues remaining, and the development of chronic inflammatory states. Identifying annulus fibrosus cell phenotypes during health, injury, and degeneration will inform reparative regeneration strategies aimed at improving annulus fibrosus healing.

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Section: Cellular Responses To Injurymentioning

confidence: 99%

Annulus fibrosus cell phenotypes in homeostasis and injury: implications for regenerative strategies

Torre

Mroz

Bartelstein

et al. 2018

Annals of the New York Academy of Sciences

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“…This is an emerging field and new biomarkers are being developed that can distinguish different sources of back pain. Serum biomarkers are quantitative and objective measurements, and can be used as indicators of biological processes involved in discogenic pain or as indicators for systematic disorders such as osteoporosis . Currently reported candidates for serum biomarkers for back pain include C‐C motif ligand 5, C‐X‐C motif ligand 6, IL‐6, high‐sensitivity C‐reactive protein, TNF‐α, IL‐1β, and type 2 collagen .…”

Section: Noninvasive Diagnostic Tools For Discogenic Painmentioning

confidence: 99%

“…Serum biomarkers are quantitative and objective measurements, and can be used as indicators of biological processes involved in discogenic pain or as indicators for systematic disorders such as osteoporosis. (52) Currently reported candidates for serum biomarkers for back pain include C-C motif ligand 5, C-X-C motif ligand 6, IL-6, high-sensitivity C-reactive protein, TNF-a, IL-1b, and type 2 collagen. (52)(53)(54)(55)(56)(57)(58)(59) Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has also been shown to distinguish discogenic LBP from the other forms of chronic back pain, and complement C3 and fibrinogen are potential serum biomarkers for discogenic back pain.…”

Section: Noninvasive Diagnostic Tools For Discogenic Painmentioning

confidence: 99%

“…(52) Currently reported candidates for serum biomarkers for back pain include C-C motif ligand 5, C-X-C motif ligand 6, IL-6, high-sensitivity C-reactive protein, TNF-a, IL-1b, and type 2 collagen. (52)(53)(54)(55)(56)(57)(58)(59) Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) has also been shown to distinguish discogenic LBP from the other forms of chronic back pain, and complement C3 and fibrinogen are potential serum biomarkers for discogenic back pain. (60) Nevertheless, serum cytokines and other biomarkers can be from a variety of sources of systemic conditions, so their specificity to discogenic back pain conditions must be validated with other methods.…”

Section: Noninvasive Diagnostic Tools For Discogenic Painmentioning

confidence: 99%

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Discogenic Back Pain: Literature Review of Definition, Diagnosis, and Treatment

et al. 2019

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Discogenic back pain is multifactorial; hence, physicians often struggle to identify the underlying source of the pain. As a result, discogenic back pain is often hard to treat—even more so when clinical treatment strategies are of questionable efficacy. Based on a broad literature review, our aim was to define discogenic back pain into a series of more specific and interacting pathologies, and to highlight the need to develop novel approaches and treatment strategies for this challenging and unmet clinical need. Discogenic pain involves degenerative changes of the intervertebral disc, including structural defects that result in biomechanical instability and inflammation. These degenerative changes in intervertebral discs closely intersect with the peripheral and central nervous systems to cause nerve sensitization and ingrowth; eventually central sensitization results in a chronic pain condition. Existing imaging modalities are nonspecific to pain symptoms, whereas discography methods that are more specific have known comorbidities based on intervertebral disc puncture and injection. As a result, alternative noninvasive and specific diagnostic methods are needed to better diagnose and identify specific conditions and sources of pain that can be more directly treated. Currently, there are many treatments/interventions for discogenic back pain. Nevertheless, many surgical approaches for discogenic pain have limited efficacy, thus accentuating the need for the development of novel treatments. Regenerative therapies, such as biologics, cell‐based therapy, intervertebral disc repair, and gene‐based therapy, offer the most promise and have many advantages over current therapies. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research

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“…IDD is a multifactorial, cell‐mediated process originating in the NP in which normal tissue turnover becomes imbalanced, favoring degradation over formation . This degradative environment is known to include metalloproteinases (MMPs) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)—catabolic enzymes that respectively degrade the two main constituents of the IVD, collagen and aggrecan .…”

Section: Introductionmentioning

confidence: 99%

Ethanol‐mediated compaction and cross‐linking enhance mechanical properties and degradation resistance while maintaining cytocompatibility of a nucleus pulposus scaffold

2019

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Intervertebral disc degeneration is a complex, cell‐mediated process originating in the nucleus pulposus (NP) and is associated with extracellular matrix catabolism leading to disc height loss and impaired spine kinematics. Previously, we developed an acellular bovine NP (ABNP) for NP replacement that emulated human NP matrix composition and supported cell seeding; however, its mechanical properties were lower than those reported for human NP. To address this, we investigated ethanol‐mediated compaction and cross‐linking to enhance the ABNP's dynamic mechanical properties and degradation resistance while maintaining its cytocompatibility. First, volumetric and mechanical effects of compaction only were confirmed by evaluating scaffolds after various immersion times in buffered 28% ethanol. It was found that compaction reached equilibrium at ~30% compaction after 45 min, and dynamic mechanical properties significantly increased 2–6× after 120 min of submersion. This was incorporated into a cross‐linking treatment, through which scaffolds were subjected to 120 min precompaction in buffered 28% ethanol prior to carbodiimide cross‐linking. Their dynamic mechanical properties were evaluated before and after accelerated degradation by ADAMTS‐5 or MMP‐13. Cytocompatibility was determined by seeding stem cells onto scaffolds and evaluating viability through metabolic activity and fluorescent staining. Compacted and cross‐linked scaffolds showed significant increases in DMA properties without detrimentally altering their cytocompatibility, and these mechanical gains were maintained following enzymatic exposure. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2488–2499, 2019.

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Inflammatory biomarkers of low back pain and disc degeneration: a review

Cited by 272 publications

References 86 publications

Annulus fibrosus cell phenotypes in homeostasis and injury: implications for regenerative strategies

Annulus fibrosus cell phenotypes in homeostasis and injury: implications for regenerative strategies

Discogenic Back Pain: Literature Review of Definition, Diagnosis, and Treatment

Ethanol‐mediated compaction and cross‐linking enhance mechanical properties and degradation resistance while maintaining cytocompatibility of a nucleus pulposus scaffold

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