Muscone protects vertebral end-plate degeneration by antiinflammatory property.
Most chronic neck pain is the result of degeneration of the cervical spine. IL-1beta may play an important role in intervertebral disc degeneration. This being the case, inhibiting IL-1beta could provide a therapeutic approach for reducing or preventing disc degeneration. Muscone reportedly relieves pain and suppresses inflammation. Therefore, we asked whether muscone, a potent antiinflammatory agent, could reduce proinflammatory cytokines in vitro (end-plate cartilage cultures) and end-plate degeneration in vivo (a rat model that induces intervertebral disc degeneration). In vitro, muscone reversed IL-1beta-induced upregulation of IL-1beta, tumor necrosis factor alpha, cyclooxygenase 2, inducible nitric oxide synthase, matrix metalloproteinase 13, aggrecanase 2, and nitric oxide and downregulation of Col2alpha1 and aggrecan. Pretreatment with muscone (6.25, 12.5, 25 mumol/L) inhibited the IL-1beta-induced phosphorylation of extracellular signal-regulated kinases 1/2 and c-Jun N-terminal kinase in a dose-dependent manner. In vivo, muscone inhibited the expression of prostaglandin E2, 6-keto-prostaglandin F1alpha, IL-1beta, and tumor necrosis factor alpha and recovered the structural distortion of the degenerative disc. Our findings suggest muscone is a promising agent for treating intervertebral disc degeneration through its antiinflammatory effects.
Liang
Qian-Qian
QQ
Institute of Spine, 725 Wan-Ping South Road, Shanghai, 200032, China.
Zhang
Min
M
Zhou
Quan
Q
Shi
Qi
Q
Wang
Yong-Jun
YJ
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002574:Cervical Vertebrae / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D019902:Chondrocytes / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D003516:Cycloparaffins / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism*; D007403:Intervertebral Disc / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D055959:Intervertebral Disc Degeneration / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D003516:Cycloparaffins; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C031021:muscone