Differential Gene Expression in Anterior and Posterior Annulus Fibrosus

Koerner, John D.; Markova, Dessislava; Yadla, Sanjay; Mendelis, Joseph; Hilibrand, Alan S.; Vaccaro, Alexander R.; Risbud, Makarand V.; Albert, Todd J.; Anderson, D. Greg; Kepler, Christopher K.

doi:10.1097/brs.0000000000000590

Cited by 19 publications

(19 citation statements)

References 42 publications

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“…5, 7) relative to either IL-6 or leptin alone. This pathway could act in vivo as leptin and IL-6 colocalise within degenerated IVDs [34]. As shown in other cell types [37][38][39], leptin can upregulate IL-6 directly via the IL-6 specific receptor.…”

Section: Discussionmentioning

confidence: 81%

“…That similar effects of leptin could be of relevance in vivo, has not been demonstrated directly in the disc. However, leptin and its receptors have been identified in degenerate regions of rat and human NP [13,33] and also in AF cells [12,34] which themselves produce leptin throughout the spectrum of degeneration [12]. The results thus indicate that a biochemical pathway involving increased leptin levels could be involved in the deleterious effects of obesity on disc degeneration and back pain.…”

Section: Discussionmentioning

confidence: 96%

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Leptin and the intervertebral disc: a biochemical link exists between obesity, intervertebral disc degeneration and low back pain—an in vitro study in a bovine model

2018

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The aim of this study was to identify the effects of leptin upon the intervertebral disc (IVD) and to determine whether these responses are potentiated within an environment of existing degeneration. Obesity is a significant risk factor for low back pain (LBP) and IVD degeneration. Adipokines, such as leptin, are novel cytokines produced primarily by adipose tissue and have been implicated in degradative and inflammatory processes. Obese individuals are known to have higher concentrations of serum leptin, and IVD cells express leptin receptors. We hypothesise that adipokines, such as leptin, mediate a biochemical link between obesity, IVD degeneration and LBP. Methods The bovine intervertebral disc was used as a model system to investigate the biochemical effects of obesity, mediated by leptin, upon the intervertebral disc. Freshly isolated cells, embedded in 3D alginate beads, were subsequently cultured under varying concentrations of leptin, alone or together with the pro-inflammatory cytokines TNF-α, IL-1β or IL-6. Responses in relation to production of nitric oxide, lactate, glycosaminoglycans and expression of anabolic and catabolic genes were analysed. Results Leptin influenced the cellular metabolism leading particularly to greater production of proteases and NO. Addition of leptin to an inflammatory environment demonstrated a marked deleterious synergistic effect with greater production of NO, MMPs and potentiation of pro-inflammatory cytokine production. Conclusions Leptin can initiate processes involved in IVD degeneration. This effect is potentiated in an environment of existing degeneration and inflammation. Hence, a biochemical mechanism may underlie the link between obesity, intervertebral disc degeneration and low back pain. Graphical abstract These slides can be retrieved under Electronic Supplementary Material.

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Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 96%

Leptin and the intervertebral disc: a biochemical link exists between obesity, intervertebral disc degeneration and low back pain—an in vitro study in a bovine model

2018

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“…Koerner et al reported that IL-4, which seemed to limit inflammatory hyperalgesia, IL-5, IL-6, M-CSF, MDC, TNF-β (lymphotoxin), EGF, IGF-1, angiogenin, and leptin showed significantly higher expression in the posterior degenerated AF than the anterior or normal one. This can be attributed to the high levels of strain on the posterior lumbar AF (Koerner et al, 2014).…”

Section: Molecular Aspects Of Intervertebral Disc Degenerationmentioning

confidence: 99%

Molecular Biology and Interactions in Intervertebral Disc Development, Homeostasis, and Degeneration, with Emphasis on Future Therapies: A Systematic Review

Aker¹,

Ghannam²,

Alzuabi³

et al. 2017

The Spine Scholar

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The unique properties of the intervertebral disc (IVD) are evident in its structural complexity and functional importance for spinal support and stability. The contributions of the different cellular and extracellular components to the function of the IVD depend on their distinctive molecular features and pathways. Disruption of these molecular pathways influences the pathological changes involved in IVD degeneration. Therefore, the molecular features of the IVD have been the focus of interest for many researchers seeking to elucidate its normal functioning, potential pathologies, and appropriate therapies. The aim of the present article is to review the molecular aspects of IVD development, specific cellular markers, and the interactions between cellular and extracellular components responsible for homeostasis, degeneration and potential therapies. The literature available via PubMed and Google Scholar was reviewed and the relevant references in review articles were searched manually. Spine

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“…Other studies suggest that asymmetric IVD degeneration is the cause, resulting in uneven loading forces that perpetuate the rate of asymmetric degeneration. Recent evidence suggests that cytokines and growth factors are differentially expressed within various locations of the IVD, likely creating regional discrepancies in the rates of cellular apoptosis, inflammation, and angiogenesis (74–76). Whether or not these differences are the result of other causative etiologies or are the instigating impetus behind the disease remains to be seen.…”

Section: Degenerative Lumbar Scoliosismentioning

confidence: 99%

Genetics Underlying an Individualized Approach to Adult Spinal Disorders

et al. 2016

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Adult spinal disorders are a significant cause of morbidity across the world and carry significant health and economic burdens. Genetic predispositions are increasingly considered for these conditions and are becoming understood. Advances in molecular technologies since the mid-1990s have made possible genetic characterizations of these diseases in many populations, and recent findings have provided insight into the underlying pathophysiologic mechanisms. These studies have made clear the genetic heterogeneity producing clinical phenotypes and suggest that individualized treatments are possible in the future. We review the genetics and heritability of cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament and perform a systematic review of the genetics of adult lumbar degenerative scoliotic deformity, highlighting recent discoveries and the potential for personalized future therapeutics for these patients.

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Differential Gene Expression in Anterior and Posterior Annulus Fibrosus

Abstract: N/A.

Cited by 19 publications

References 42 publications

Leptin and the intervertebral disc: a biochemical link exists between obesity, intervertebral disc degeneration and low back pain—an in vitro study in a bovine model

Leptin and the intervertebral disc: a biochemical link exists between obesity, intervertebral disc degeneration and low back pain—an in vitro study in a bovine model

Molecular Biology and Interactions in Intervertebral Disc Development, Homeostasis, and Degeneration, with Emphasis on Future Therapies: A Systematic Review

Genetics Underlying an Individualized Approach to Adult Spinal Disorders

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