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

• Published in: International journal of molecular sciences Vol. 24; no. 10; p. 8566
• Main Authors: Ohnishi, Hiroki, Zhang, Zhongying, Yurube, Takashi, Takeoka, Yoshiki, Kanda, Yutaro, Tsujimoto, Ryu, Miyazaki, Kunihiko, Matsuo, Tomoya, Ryu, Masao, Kumagai, Naotoshi, Kuroshima, Kohei, Hiranaka, Yoshiaki, Kuroda, Ryosuke, Kakutani, Kenichiro
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.05.2023; MDPI
• Subjects: Adenosine kinase; Adenosine monophosphate; Adenylic acid; Adipocytes; Adiponectin; Adiponectin - metabolism; AdipoRon; Agonists; Analysis; Animals; Anti-Inflammatory Agents - metabolism; Anti-inflammatory drugs; Cartilage; Cartilage diseases; Cytokines; Degeneration; Degenerative disc disease; disc degeneration; Experiments; Extracellular matrix; Gene expression; Health aspects; Humans; Inflammatory diseases; Interleukins; intervertebral disc (IVD); Intervertebral Disc - metabolism; Intervertebral Disc Degeneration - metabolism; Intervertebral discs; Kinases; Metabolism; Nucleus pulposus; Obesity; Phosphorylation; Physiological aspects; Physiological effects; Polymerase chain reaction; puncture model; Rats; Receptors, Adiponectin - metabolism; Scientific equipment and supplies industry; spine; Tumor necrosis factor-TNF; Western blotting; United States; Japan; intervertebral disc (IVD); adiponectin; disc degeneration; AdipoRon; spine; puncture model
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24108566

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 ( < 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.