Abstract

Objective

Omentin-1 is a newly discovered metabolic regulatory adipokine. Studies have shown that omentin-1 possesses pleiotropic effects in different types of cells. This study aims to investigate the regulation by omentin-1 on mitochondrial biogenesis in chondrocytes.

Methodology

C-28/I2 chondrocytes were treated with omentin-1 (150 and 300 ng/ml) for 24 h. The expression of mitochondrial regulators, markers and the DNA copy was assessed. The mitochondrial morphology was observed by electron microscopy. The mitochondrial respiratory rate and ATP production in chondrocytes were measured by cell lysates.

Results

Omentin-1 treatment up-regulated PGC-1α, NRF-1 and mitochondrial transcription factor A (TFAM) in cultured chondrocytes, indicating that omentin-1 could be involved in the regulation of mitochondrial function. Omentin-1 promoted mtDNA/nDNA and four mitochondrial genes (Tomm20, Tomm40, Timm9 and Atp5c1), mRNA transcripts as well as two mitochondrial protein expressions (SDHB and MTCO1). At a cellular level, omentin-1 enhanced the mitochondrial respiratory rate and ATP production. Mechanistically, we proved that omentin-1 increased AMPKα activation, and the blockage of AMPKα by its inhibitor compound C abolished the inductive effect of omentin-1 on PGC1α expression and mtDNA/nDNA ratio, indicating that the effect of omentin-1 is dependent on AMPKα activation.

Conclusion

Omentin-1 is a positive regulator of mitochondrial biogenesis in chondrocytes, and its action is dependent on the AMPK-PGC1α pathway. This study, therefore, implies that omentin-1 has the potential to remedy chondrocyte damage in the prevention and treatment of osteoarthritis.

中文翻译：

---

Omentin-1 通过软骨细胞中的 PGC1α-AMPK 通路促进线粒体生物发生

摘要

客观的

Omentin-1 是一种新发现的代谢调节脂肪因子。研究表明，omentin-1 在不同类型的细胞中具有多效性。本研究旨在研究 omentin-1 对软骨细胞线粒体生物合成的调控。

方法

C-28/I2 软骨细胞用 omentin-1（150 和 300 ng/ml）处理 24 小时。评估了线粒体调节剂、标记物和 DNA 拷贝的表达。通过电子显微镜观察线粒体形态。通过细胞裂解物测量软骨细胞中的线粒体呼吸速率和 ATP 产生。

结果

Omentin-1 处理上调培养的软骨细胞中的 PGC-1α、NRF-1 和线粒体转录因子 A (TFAM)，表明 Omentin-1 可能参与线粒体功能的调节。Omentin-1 促进 mtDNA/nDNA 和四种线粒体基因（Tomm20、Tomm40、Timm9 和 Atp5c1）、mRNA 转录物以及两种线粒体蛋白表达（SDHB 和 MTCO1）。在细胞水平上，omentin-1 增强了线粒体呼吸频率和 ATP 的产生。从机制上讲，我们证明 omentin-1 增加了 AMPKα 的激活，其抑制剂化合物 C 对 AMPKα 的阻断消除了 omentin-1 对 PGC1α 表达和 mtDNA/nDNA 比率的诱导作用，表明 omentin-1 的作用依赖于AMPKα 激活。

结论

Omentin-1 是软骨细胞线粒体生物发生的正调节因子，其作用依赖于 AMPK-PGC1α 通路。因此，本研究暗示 omentin-1 在预防和治疗骨关节炎方面具有修复软骨细胞损伤的潜力。