| First Author | Teng P | Year | 2019 |
| Journal | J Immunol | Volume | 203 |
| Issue | 2 | Pages | 485-492 |
| PubMed ID | 31152077 | Mgi Jnum | J:276910 |
| Mgi Id | MGI:6323706 | Doi | 10.4049/jimmunol.1801513 |
| Citation | Teng P, et al. (2019) Nicotine Attenuates Osteoarthritis Pain and Matrix Metalloproteinase-9 Expression via the alpha7 Nicotinic Acetylcholine Receptor. J Immunol 203(2):485-492 |
| abstractText | Osteoarthritis (OA) is a degenerative joint disease that causes chronic disability among the elderly. Despite recent advances in symptomatic management of OA by pharmacological and surgical approaches, there remains a lack of optimal approaches to manage inflammation in the joints, which causes cartilage degradation and pain. In this study, we investigated the efficacy and underlying mechanisms of nicotine exposure in attenuating joint inflammation, cartilage degradation, and pain in a mouse model of OA. A mouse model of OA was induced by injection of monosodium iodoacetate into the knee joint. Cell culture models were also used to study the efficacy and underlying mechanisms of nicotine treatment in attenuating symptoms of OA. Nicotine treatment reduced mechanical allodynia, cartilage degradation, and the upregulation of matrix metalloproteinase-9 (MMP-9), a hallmark of joint inflammation in OA, in mice treated with monosodium iodoacetate. The effects of nicotine were abolished by the selective alpha7 nicotinic acetylcholine receptor (nAChR) blocker, methyllycaconitine . In RAW264.7 cells and murine primary bone marrow-derived macrophages, nicotine significantly inhibited MMP-9 production induced by LPS. In addition, nicotine significantly enhanced PI3K/Akt and inhibited NF-kappaB translocation from the cytosol to the nucleus in an alpha7-nAChR-dependent manner, suggesting that nicotine acts on alpha7-nAChRs to inhibit MMP-9 production by macrophages through modulation of the PI3K/Akt-NF-kappaB pathway. Our results provide novel evidence that nicotine can attenuate joint inflammation and pain in experimental OA via alpha7-nAChRs. alpha7-nAChR could thus serve as a highly promising target to manage joint inflammation and pain in OA. |
