Abstract
PurposeThe 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.MethodsThe 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.ResultsLeptin 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.ConclusionsLeptin 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 abstractThese slides can be retrieved under Electronic Supplementary Material.
Highlights
Materials and methodsLow back pain (LBP) is the leading cause of years lived with disability, worldwide [1]
In the annulus fibrosus (AF), there was no discernible change in lactate production with increasing leptin concentration
The nucleus pulposus (NP) showed a trend for a fall in metabolism with the increase in leptin concentration, but this did not reach statistical significance (Fig. 1a)
Summary
Materials and methodsLow back pain (LBP) is the leading cause of years lived with disability, worldwide [1]. While the pathogenesis of low back pain is complex and not well understood, many authors have linked LBP to intervertebral disc (IVD) degeneration [2,3,4] Obesity is another public health epidemic, described as one of the most important contributors to the worldwide disease burden [5]. Leptin, discovered in 1994, is the prototypical adipokine and acts primarily to regulate appetite [10] It is the primary biochemical mediator of the inflammatory, degradative and pain-related effects of obesity and, while primarily the product of adipocytes, is produced by multiple other tissues including cartilages [11,12,13]
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