Inflammaging determines health and disease in lumbar discs: evidence from differing proteomic signatures of healthy, aging and degenerating discs

Rajasekaran, S.; Tangavel, Chitraa; Anand, Sri Vijay; Soundararajan, Dilip Chand Raja; Nayagam, Sharon Miracle; Matchado, Monica Steffi; Raveendran, M.; Shetty, Ajoy Prasad; Kanna, Rishi Mugesh; Dharmalingam, K.

doi:10.1016/j.spinee.2019.05.170

Cited by 12 publications

(15 citation statements)

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“…Microbiological studies on disc biopsies show mixed results, and it is still uncertain whether the observed C.acnes in such studies are partly or completely explained by contamination. However, proteomic analyses of degenerated discs did find evidence of response to gram positive bacterial infection that is difficult to explain by contamination [27]. Further trials with antibiotic treatment in back pain should preferably be performed on patients with confirmed infection, either microbiologically or other methods.…”

Section: Discussionmentioning

confidence: 99%

Clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes - secondary analyses of a randomised, placebo-controlled trial (the AIM study)

Bråten

Grøvle

Espeland

et al. 2020

BMC Musculoskelet Disord

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Background: Randomised trials on antibiotic treatment for patients with chronic low back pain and vertebral endplate changes visible on MRI (Modic changes) have shown mixed results. A possible explanation might be a real treatment effect in subgroups of the study populations. The purpose of the present study was to explore potential clinical effect modifiers of 3-months oral amoxicillin treatment in patients with chronic low back pain and type I or II Modic changes at the level of a previous lumbar disc herniation. Methods: We performed analyses of effect modifiers on data from AIM, a double-blind parallel-group multicentre trial. One hundred eighty patients with chronic low back pain, previous disc herniation, Modic change type I (n = 118) or type II (n = 62) were randomised to 3-months oral treatment with 750 mg amoxicillin (n = 89) or placebo (n = 91) three times daily. The primary outcome was the Roland-Morris Disability Questionnaire (RMDQ) score (possible values 0-24) at 1-year follow-up in the intention-to-treat population. The predefined minimal clinically important between-group mean difference was 4 RMDQ points (not reached in the primary analysis of AIM). Predefined baseline characteristics were analysed as potential effect modifiers, four primary (type I Modic changes, previous disc surgery, positive pain provocation test, high CRP) and five exploratory (disturbed sleep, constant low back pain, short duration of low back pain, younger age, and male) using ANCOVA with interaction terms.

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Section: Discussionmentioning

confidence: 99%

Clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes - secondary analyses of a randomised, placebo-controlled trial (the AIM study)

Bråten

Grøvle

Espeland

et al. 2020

BMC Musculoskelet Disord

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“…Furthermore, the enhanced secretion of proinflammatory and catabolic factors by senescent cells may favour the senescence of neighbouring healthy cells thus precipitating a sort of degenerative domino effect. The strong relationships among IDD, cell senescence, and inflammation have been recently described as "inflammaging," a process with distinctive biological and proteomic features typical of aging and degenerating IVDs [68].…”

Section: Intervertebral Disc Degeneration: a Great Challenge For Cellmentioning

confidence: 99%

Interaction between Mesenchymal Stem Cells and Intervertebral Disc Microenvironment: From Cell Therapy to Tissue Engineering

Vadalà

Ambrosio

Russo

et al. 2019

Stem Cells International

112

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Low back pain (LBP) in one of the most disabling symptoms affecting nearly 80% of the population worldwide. Its primary cause seems to be intervertebral disc degeneration (IDD): a chronic and progressive process characterized by loss of viable cells and extracellular matrix (ECM) breakdown within the intervertebral disc (IVD) especially in its inner region, the nucleus pulposus (NP). Over the last decades, innovative biological treatments have been investigated in order to restore the original healthy IVD environment and achieve disc regeneration. Mesenchymal stem cells (MSCs) have been widely exploited in regenerative medicine for their capacity to be easily harvested and be able to differentiate along the osteogenic, chondrogenic, and adipogenic lineages and to secrete a wide range of trophic factors that promote tissue homeostasis along with immunomodulation and anti-inflammation. Several in vitro and preclinical studies have demonstrated that MSCs are able to acquire a NP cell-like phenotype and to synthesize structural components of the ECM as well as trophic and anti-inflammatory mediators that may support resident cell activity. However, due to its unique anatomical location and function, the IVD presents distinctive features: avascularity, hypoxia, low glucose concentration, low pH, hyperosmolarity, and mechanical loading. Such conditions establish a hostile microenvironment for both resident and exogenously administered cells, which limited the efficacy of intradiscal cell therapy in diverse investigations. This review is aimed at describing the characteristics of the healthy and degenerated IVD microenvironment and how such features influence both resident cells and MSC viability and biological activity. Furthermore, we focused on how recent research has tried to overcome the obstacles coming from the IVD microenvironment by developing innovative cell therapies and functionalized bioscaffolds.

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“…Nevertheless, human-animal differences in cellular phenotypes and mechanical loading physiologies mean that these findings might not translate to the human scenario. So far, human proteomic studies have compared IVDs with other cartilaginous tissues (Onnerfjord et al, 2012a); and have shown increases in fibrotic changes in ageing and degeneration (Yee et al, 2016), a role for inflammation in degenerated discs (Rajasekaran et al, 2020), the presence of haemoglobins and immunoglobulins in discs with spondylolisthesis and herniation (Maseda et al, 2016), and changes in proteins related to cell adhesion and migration in IDD (Sarath Babu et al, 2016). The reported human disc proteomes were limited in the numbers of proteins identified and finer compartmentalisation within the IVD, and disc levels along the lumbar spine have yet to be studied.…”

Section: Introductionmentioning

confidence: 99%

DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics

Tam

Chen

Yee

et al. 2020

eLife

114

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The spatiotemporal proteome of the intervertebral disc (IVD) underpins its integrity and function. We present DIPPER, a deep and comprehensive IVD proteomic resource comprising 94 genome-wide profiles from 17 individuals. To begin with, protein modules defining key directional trends spanning the lateral and anteroposterior axes were derived from high-resolution spatial proteomes of intact young cadaveric lumbar IVDs. They revealed novel region-specific profiles of regulatory activities and displayed potential paths of deconstruction in the level- and location-matched aged cadaveric discs. Machine learning methods predicted a ‘hydration matrisome’ that connects extracellular matrix with MRI intensity. Importantly, the static proteome used as point-references can be integrated with dynamic proteome (SILAC/degradome) and transcriptome data from multiple clinical samples, enhancing robustness and clinical relevance. The data, findings, and methodology, available on a web interface (http://www.sbms.hku.hk/dclab/DIPPER/), will be valuable references in the field of IVD biology and proteomic analytics.

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Inflammaging determines health and disease in lumbar discs: evidence from differing proteomic signatures of healthy, aging and degenerating discs

Cited by 12 publications

References 0 publications

Clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes - secondary analyses of a randomised, placebo-controlled trial (the AIM study)

Clinical effect modifiers of antibiotic treatment in patients with chronic low back pain and Modic changes - secondary analyses of a randomised, placebo-controlled trial (the AIM study)

Interaction between Mesenchymal Stem Cells and Intervertebral Disc Microenvironment: From Cell Therapy to Tissue Engineering

DIPPER, a spatiotemporal proteomics atlas of human intervertebral discs for exploring ageing and degeneration dynamics

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