Role of Wnt-5A in interleukin-1beta-induced matrix metalloproteinase expression in rabbit temporomandibular joint condylar chondrocytes.
OBJECTIVE
To determine the possible involvement and regulatory mechanisms of Wnt-5A signaling in interleukin-1beta (IL-1beta)-induced increase in matrix metalloproteinase 1 (MMP-1), MMP-3, MMP-9, and MMP-13 expression in temporomandibular joint (TMJ) condylar chondrocytes.


METHODS
Primary rabbit condylar chondrocytes were treated with IL-1beta, purified Wnt-5A protein, or both and transfected with Wnt-5A expression vector. Expression of Wnt-5A, MMP-1, MMP-3, MMP-9, MMP-13, and type II collagen, as well as cell morphologic changes, were examined. To explore the mechanisms of action of Wnt-5A, the accumulation and nuclear translocation of beta-catenin, the transcription activity of the beta-catenin-Tcf/Lef complex, phosphorylated JNK, phosphorylated ERK, and phosphorylated p38 were analyzed. SP600125, a JNK inhibitor, was used to investigate the role of the JNK pathway in Wnt-5A induction of MMP-1, MMP-3, MMP-9, and MMP-13.


RESULTS
Treatment of rabbit condylar chondrocytes with IL-1beta up-regulated Wnt-5A expression. Purified Wnt-5A protein and transfection with Wnt-5A expression vector promoted the expression of MMP-1, MMP-3, MMP-9, and MMP-13. Wnt-5A did not cause accumulation and nuclear translocation of beta-catenin or activation of the beta-catenin-Tcf/Lef transcription complex. Instead, Wnt-5A activated JNK, and an inhibitor of JNK blocked the Wnt-5A-induced up-regulated expression of MMPs.


CONCLUSIONS
These findings indicate that IL-1beta up-regulates Wnt-5A, and the activation of Wnt-5A signaling induces the expression of MMP-1, MMP-3, MMP-9, and MMP-13 via the JNK signaling pathway in rabbit TMJ condylar chondrocytes. Blockage of JNK signaling impairs the Wnt-5A-induced up-regulation of MMPs. Thus, Wnt-5A may be associated with cartilage destruction by promoting the expression of MMPs.
Ge
Xianpeng
X
Center for Temporomandibular Disorders and Orofacial Pain, Peking University School and Hospital of Stomatology, 22 Zhongguancun Nandajie, Beijing, China.
Ma
Xuchen
X
Meng
Juanhong
J
Zhang
Chenguang
C
Ma
Kangtao
K
Zhou
Chunyan
C
D000818:Animals; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D024043:Collagen Type II / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D053583:Interleukin-1beta / Q000502:physiology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology; D013704:Temporomandibular Joint / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D051153:Wnt Proteins / Q000378:metabolism* / Q000494:pharmacology; D051176:beta Catenin / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D024043:Collagen Type II; D053583:Interleukin-1beta; D051153:Wnt Proteins; D051176:beta Catenin; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D053509:Matrix Metalloproteinase 13; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1