Wei Lu1, Zhenfei Ding1, Fuen Liu1, Wenshan Shan1, Chao Cheng2, Jiegou Xu3, Wei He3, Wei Huang4, Junting Ma5, Zongsheng Yin6. 1. Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, 218#Ji Xi Road, Hefei, 230032, Anhui, China. 2. Department of Orthopaedics, The Fourth Affiliated Hospital of Anhui Medical University, 372#Tun Xi Road, Hefei, 230032, Anhui, China. 3. School of Basic Medical Sciences, Anhui Medical University, 81#Mei Shan Road, Hefei, 230032, Anhui, China. 4. Department of Orthopaedics, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, 17#Lu Jiang Road, Hefei, 230001, Anhui, China. Electronic address: ahslyyhwei@126.com. 5. School of Basic Medical Sciences, Anhui Medical University, 81#Mei Shan Road, Hefei, 230032, Anhui, China. Electronic address: majunting@ahmu.edu.cn. 6. Department of Orthopaedics, The First Affiliated Hospital of Anhui Medical University, 218#Ji Xi Road, Hefei, 230032, Anhui, China. Electronic address: anhuiyzs@126.com.
Abstract
BACKGROUND: The progressive loss of cartilage matrix and the breakdown of articular cartilage induced by inflammation play an essential role in osteoarthritis (OA) pathogenesis. Dopamine (DA) is a critical neurotransmitter that is not only involved in controlling exercise, emotion, cognition and neuroendocrine activity but also has anti-inflammatory effects. This study aimed to investigate the effects of DA on OA in vitro and in vivo. METHODS: OA progression was evaluated in a mouse model with surgically induced destabilization of the medial meniscus. Cartilage degradation and OA were analyzed using Safranin O/Fast Green staining. Additionally, qRT-PCR and Western blotting were applied to detect catabolic and anabolic factors involved in cartilage degeneration and underlying mechanisms in OA chondrocytes treated with Interleukin-1β. RESULTS: In vitro, DA treatment inhibited the production of inducible nitric oxide synthase, cyclooxygenase-2, matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13, while increasing type II collagen and glycosaminoglycan content. Mechanistically, DA reversed IL-1β-treated nuclear factor-kappa B activation and JAK2/STAT3 phosphorylation. Furthermore, DA suppressed the degradation of cartilage matrix and reduced Osteoarthritis Research Society International scores in the surgically induced OA models. CONCLUSION: DA may be a novel therapeutic agent for OA treatment.
BACKGROUND: The progressive loss of cartilage matrix and the breakdown of articular cartilage induced by inflammation play an essential role in osteoarthritis (OA) pathogenesis. Dopamine (DA) is a critical neurotransmitter that is not only involved in controlling exercise, emotion, cognition and neuroendocrine activity but also has anti-inflammatory effects. This study aimed to investigate the effects of DA on OA in vitro and in vivo. METHODS:OA progression was evaluated in a mouse model with surgically induced destabilization of the medial meniscus. Cartilage degradation and OA were analyzed using Safranin O/Fast Green staining. Additionally, qRT-PCR and Western blotting were applied to detect catabolic and anabolic factors involved in cartilage degeneration and underlying mechanisms in OA chondrocytes treated with Interleukin-1β. RESULTS: In vitro, DA treatment inhibited the production of inducible nitric oxide synthase, cyclooxygenase-2, matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13, while increasing type II collagen and glycosaminoglycan content. Mechanistically, DA reversed IL-1β-treated nuclear factor-kappa B activation and JAK2/STAT3 phosphorylation. Furthermore, DA suppressed the degradation of cartilage matrix and reduced Osteoarthritis Research Society International scores in the surgically induced OA models. CONCLUSION:DA may be a novel therapeutic agent for OA treatment.