Stimulation of α7-nAChRs coordinates autophagy and apoptosis signaling in experimental knee osteoarthritis.

Abstract

Osteoarthritis (OA) is the most common chronic joint disease in the elderly population. Growing evidence indicates that a balance between autophagy and apoptosis in chondrocytes plays a key role in OA's cartilage degradation. Thus, drugs targeting the balance between apoptosis and autophagy are potential therapeutic approaches for OA treatment. In previous studies, we found that the activation of α7 nicotinic acetylcholine receptors (α7-nAChRs) alleviated monosodium iodoacetate (MIA)-induced joint degradation and osteoarthritis pain. To explore the potential functions of α7-nAChRs in autophagy and apoptosis signaling in knee OA, we compared the expression of α7-nAChRs in human knee articular cartilage tissues from normal humans and OA patients. We found that knee joint cartilage tissues of OA patients showed decreased α7-nAChRs and an imbalance between autophagy and apoptosis. Next, we observed that α7-nAChRs deficiency did not affect cartilage degradation in OA development but reversed the beneficial effects of nicotine on mechanical allodynia, cartilage degradation, and an MIA-induced switch from autophagy to apoptosis. Unlike in vivo studies, we found that primary chondrocytes from α7-nAChRs knockout (KO) mice showed decreased LC3 levels under normal conditions and were more sensitive toward MIA-induced apoptosis. Finally, we found that α7-nAChRs deficiency increased the phosphorylation of mTOR after MIA treatment, which can also be observed in OA patients' tissues. Thus, our findings not only confirmed that nicotine alleviated MIA-induced pain behavior and cartilage degradation via stimulating the α7-nAChRs/mTOR signal pathway but found the potential role of α7-nAChRs in mediating the balance between apoptosis and autophagy.

• Authors: Yuan Liu, Shi Xu, Haijun Zhang, Kaoliang Qian, Jiachen Huang, Xianger Gu, Yan Li, Yi Fan, Jun Hu
• Journal: Cell death & disease (Cell Death Dis) Vol. 12 Issue 5 Pg. 448 (05 05 2021) ISSN: 2041-4889 [Electronic] England
• PMID: 33953172 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• alpha7 Nicotinic Acetylcholine Receptor

Topics

• Animals
• Apoptosis (physiology)
• Autophagy (physiology)
• Disease Models, Animal
• Humans
• Male
• Mice
• Osteoarthritis, Knee (genetics)
• Signal Transduction
• alpha7 Nicotinic Acetylcholine Receptor (metabolism)