School of Medicine, College of Medicine, Taipei Medical University, Taipei.
Department of Neurosurgery, Taipei Medical University Hospital, Taipei.
Cell Transplant. 2021 Jan-Dec;30:9636897211045319. doi: 10.1177/09636897211045319.
Apart from aging process, adult intervertebral disc (IVD) undergoes various degenerative processes. However, the nicotine has not been well identified as a contributing etiology. According to a few studies, nicotine ingestion through smoking, air or clothing may significantly accumulate in active as well as passive smokers. Since nicotine has been demonstrated to adversely impact various physiological processes, such as sympathetic nervous system, leading to impaired vasculature and cellular apoptosis, we aimed to investigate whether nicotine could induce IVD degeneration. In particular, we evaluated dose-dependent impact of nicotine in vitro to simulate its chronic accumulation, which was later treated by platelet-derived biomaterials (PDB). Further, during in vivo studies, mice were subcutaneously administered with nicotine to examine IVD-associated pathologic changes. The results revealed that nicotine could significantly reduce chondrocytes and chondrogenic indicators (Sox, Col II and aggrecan). Mice with nicotine treatment also exhibited malformed IVD structure with decreased Col II as well as proteoglycans, which was significantly increased after PDB administration for 4 weeks. Mechanistically, PDB significantly restored the levels of IGF-1 signaling proteins, particularly pIGF-1 R, pAKT, and IRS-1, modulating ECM synthesis by chondrocytes. Conclusively, the PDB impart reparative and tissue regenerative processes by inhibiting nicotine-initiated IVD degeneration, through regulating IGF-1/AKT/IRS-1 signaling axis.
除了衰老过程，成人椎间盘（IVD）还会经历各种退行性过程。然而，尼古丁是否是导致这种退行性过程的病因尚未得到充分证实。根据一些研究，通过吸烟、空气或衣物摄入的尼古丁可能会在主动和被动吸烟者体内大量积累。由于尼古丁已被证明会对各种生理过程产生不利影响，例如交感神经系统，导致血管和细胞凋亡受损，我们旨在研究尼古丁是否会导致 IVD 退化。特别是，我们评估了尼古丁在体外的剂量依赖性影响，以模拟其慢性积累，然后用血小板衍生生物材料（PDB）进行处理。此外，在体内研究中，通过皮下注射尼古丁来研究与 IVD 相关的病理变化。结果表明，尼古丁可显著减少软骨细胞和软骨生成指标（Sox、Col II 和 aggrecan）。用尼古丁处理的小鼠还表现出畸形的 IVD 结构，Col II 和蛋白聚糖减少，而在用 PDB 处理 4 周后，这些物质的含量显著增加。从机制上讲，PDB 通过调节 IGF-1 信号蛋白（特别是 pIGF-1R、pAKT 和 IRS-1）的水平，恢复细胞外基质的合成，从而显著恢复 IGF-1 信号通路，从而抑制尼古丁引发的 IVD 退化。综上所述，PDB 通过调节 IGF-1/AKT/IRS-1 信号轴，抑制尼古丁引起的 IVD 退变，从而发挥修复和组织再生作用。
