Plumbagin Prevents IL-1β-Induced Inflammatory Response in Human Osteoarthritis Chondrocytes and Prevents the Progression of Osteoarthritis in Mice.
Inflammation and inflammatory cytokines have been reported to play vital roles in the development of osteoarthritis (OA). Plumbagin, a quinonoid compound extracted from the roots of medicinal herbs of the Plumbago genus, has been reported to have anti-inflammatory effects. However, the anti-inflammatory effects of plumbagin on OA have not been reported. This study aimed to assess the effects of plumbagin on human OA chondrocytes and in a mouse model of OA induced by destabilization of the medial meniscus (DMM). In vitro, human OA chondrocytes were pretreated with plumbagin (2, 5, 10 μM) for 2 h and subsequently stimulated with IL-1β for 24 h. Production of NO, PGE2, MMP-1, MMP-3, and MMP-13 was evaluated by the Griess reagent and ELISAs. The messenger RNA (mRNA) expression of COX-2, iNOS, MMP-1, MMP-3, MMP-13, aggrecan, and collagen-II was measured by real-time PCR. The protein expression of COX-2, iNOS, p65, p-p65, IκBα, and p-IκBα was detected by Western blot. The protein expression of collagen-II was evaluated by immunofluorescence. In vivo, the severity of OA was determined by histological analysis. We found that plumbagin significantly inhibited the IL-1β-induced production of NO and PGE2; expression of COX-2, iNOS, MMP-1, MMP-3, and MMP-13; and degradation of aggrecan and collagen-II. Furthermore, plumbagin dramatically suppressed IL-1β-stimulated NF-κB activation. In vivo, treatment of plumbagin not only prevented the destruction of cartilage and the thickening of subchondral bone but also relieved synovitis in mice OA models. Taken together, these results suggest that plumbagin may be a potential agent in the treatment of OA.
Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Xi Road, Wenzhou, 325000, China.
Wenhao
W
Zheng
Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Xi Road, Wenzhou, 325000, China.
Zhenyu
Z
Tao
Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Xi Road, Wenzhou, 325000, China.
Chunhui
C
Chen
Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Xi Road, Wenzhou, 325000, China.
Chuanxu
C
Zhang
Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Xi Road, Wenzhou, 325000, China.
Hui
H
Zhang
Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Xi Road, Wenzhou, 325000, China.
Xiaozhou
X
Ying
Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109 Xueyuan Xi Road, Wenzhou, 325000, China. chenhuafey@126.com.
Hua
http://orcid.org/0000-0003-3086-2317
H
Chen
D000276:Adjuvants, Immunologic; D000818:Animals; D019902:Chondrocytes / Q000187:drug effects / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors*; D051379:Mice; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology* / Q000627:therapeutic use; D010003:Osteoarthritis / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction / Q000187:drug effects
D000276:Adjuvants, Immunologic; D053583:Interleukin-1beta; D016328:NF-kappa B; D009285:Naphthoquinones; C014758:plumbagin
IL-1β; NF-κB; chondrocytes; osteoarthritis; plumbagin