Anti-Inflammatory Effects of Adiponectin Receptor Agonist AdipoRon against Intervertebral Disc Degeneration

Int J Mol Sci. 2023 May 10;24(10):8566. doi: 10.3390/ijms24108566.

Abstract

Adiponectin, a hormone secreted by adipocytes, has anti-inflammatory effects and is involved in various physiological and pathological processes such as obesity, inflammatory diseases, and cartilage diseases. However, the function of adiponectin in intervertebral disc (IVD) degeneration is not well understood. This study aimed to elucidate the effects of AdipoRon, an agonist of adiponectin receptor, on human IVD nucleus pulposus (NP) cells, using a three-dimensional in vitro culturing system. This study also aimed to elucidate the effects of AdipoRon on rat tail IVD tissues using an in vivo puncture-induced IVD degeneration model. Analysis using quantitative polymerase chain reaction demonstrated the downregulation of gene expression of proinflammatory and catabolic factors by interleukin (IL)-1β (10 ng/mL) in human IVD NP cells treated with AdipoRon (2 μM). Furthermore, western blotting showed AdipoRon-induced suppression of p65 phosphorylation (p < 0.01) under IL-1β stimulation in the adenosine monophosphate-activated protein kinase (AMPK) pathway. Intradiscal administration of AdipoRon was effective in alleviating the radiologic height loss induced by annular puncture of rat tail IVD, histomorphological degeneration, production of extracellular matrix catabolic factors, and expression of proinflammatory cytokines. Therefore, AdipoRon could be a new therapeutic candidate for alleviating the early stage of IVD degeneration.

Keywords: AdipoRon; adiponectin; disc degeneration; intervertebral disc (IVD); puncture model; spine.

MeSH terms

  • Adiponectin / metabolism
  • Animals
  • Anti-Inflammatory Agents / metabolism
  • Humans
  • Intervertebral Disc Degeneration* / metabolism
  • Intervertebral Disc* / metabolism
  • Rats
  • Receptors, Adiponectin / metabolism

Substances

  • Adiponectin
  • Receptors, Adiponectin
  • AdipoRon
  • Anti-Inflammatory Agents

Grants and funding

This research was funded by JSPS KAKENHI (Grant Number JP20K09480). The fundershad no role in the design of the study, data collection, analyses, or interpretation, in the writing of themanuscript, or in the decision to publish the results.