An adiponectin receptor agonist promote osteogenesis via regulating bone-fat balance

脂联素受体激动剂通过调节骨脂平衡促进成骨

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作者:Hanghang Liu, Shibo Liu, Huanzhong Ji, Qiucheng Zhao, Yao Liu, Pei Hu, En Luo

Conclusions

Our study demonstrated a pro-osteogenic, anti-adipogenic and anti-osteoclastogenic effect of adiponectin receptor activation in young mice, which suggested adiponectin receptor signalling was involved in bone regeneration and bone-fat balance regulation.

Methods

We primarily applied a newly found specific activator for adiponectin receptor, AdipoRon, to treat bone metabolism-related cells to investigate the role of Adiponectin receptor signals on bone-fat balance. We then established femur defect mouse model and treated them with AdipoRon to see whether adiponectin receptor activation could promote bone regeneration.

Results

We found that AdipoRon could slightly inhibit the proliferation of pre-osteoblast and pre-osteoclast, but AdipoRon showed no effect on the viability of mesenchymal stromal cells. AdipoRon could remarkably promote cell migration of mesenchymal stromal cells. Additionally, AdipoRon promoted osteogenesis in both pre-osteoblasts and mesenchymal cells. Besides, AdipoRon significantly inhibited osteoclastogenesis via its direct impact on pre-osteoclast and its indirect inhibition of RANKL in osteoblast. Moreover, mesenchymal stromal stems cells showed obviously decreased adipogenesis when treated with AdipoRon. Consistently, AdipoRon-treated mice showed faster bone regeneration and repressed adipogenesis. Conclusions: Our study demonstrated a pro-osteogenic, anti-adipogenic and anti-osteoclastogenic effect of adiponectin receptor activation in young mice, which suggested adiponectin receptor signalling was involved in bone regeneration and bone-fat balance regulation.

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