The secreted protein WNT5A regulates condylar chondrocyte proliferation, hypertrophy and migration
The secreted protein WNT5A regulates condylar chondrocyte proliferation, hypertrophy and migration
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DOI：
10.1016/j.archoralbio.2017.06.019
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发表时间：
2017-10-01
影响因子：
3
通讯作者：
Ma, Xuchen
中科院分区：
文献类型：
--
作者：
Ge, Xianpeng;Shi, Ruirui;Ma, Xuchen
目的：我们的前期研究表明，WNT 5A，一个非经典的WNT通路的成员，参与白细胞介素-1 β诱导的颞下颌关节（TMJ）髁突软骨细胞基质金属蛋白酶的表达。本研究旨在进一步探讨WNT 5A在TMJ软骨生物学中的作用。方法：采用机械法（稳定张口）建立早期TMJ骨关节炎样大鼠模型。检测髁突软骨变化过程中WNT 5A基因和蛋白水平的变化。在体外WNT 5A功能获得或丧失后，分析WNT 5A对软骨细胞增殖、肥大和迁移的影响。使用c-Jun N-末端激酶（JNK）抑制剂SP 600125来评估JNK通路在WNT 5A的这些作用中的参与。检测细胞周期调节因子c-MYC和Cyclin D1的表达和转录活性，以确定WNT 5A调节软骨细胞增殖的机制。结果：在TMJ骨关节炎样模型早期，WNT 5A在大鼠髁突软骨中表达显著上调。激活WNT 5A促进髁突软骨细胞增殖、肥大和迁移。相反，抑制软骨细胞中的WNT 5A活性会降低其增殖、肥大和迁移。JNK通路的抑制剂SP 600125阻断JNK通路，削弱了WNT 5A对软骨细胞的这些作用。结论：WNT 5A调控髁突软骨细胞的增殖、肥大和迁移。这些发现为WNT 5A信号在TMJ软骨生物学中的作用及其在未来TMJ退行性疾病治疗中的潜力提供了新的见解。
Objective: Our previous study showed that WNT5A, a member of the noncanonical WNT pathway, is involved in interleukin-lbeta induced matrix metalloproteinase expression in temporomandibular joint (TMJ) condylar chondrocytes. The purpose of this study is to further explore the roles of WNT5A in cartilage biology of the TMJ.Methods: An early TMJ osteoarthritis-like rat model was constructed by a mechanical method (steady mouth opening). The gene and protein levels of WNT5A during the condylar cartilage changes were measured. Effects of WNT5A on chondrocyte proliferation, hypertrophy and migration were analyzed after WNT5A gain or loss of function in vitro. A c-Jun N-terminal kinase (JNK) inhibitor SP600125 was used to evaluate the involvement of JNK pathway in these effects of WNT5A. The expression and transcription activity of cell cycle regulators c-MYC and Cyclin Dl were examined to determine the mechanism behind WNT5A regulation of chondrocyte proliferation.Results: WNT5A was significantly upregulated in the condylar cartilage of rats in the early TMJ osteoarthritis-like model. Activating WNT5A facilitated condylar chondrocyte proliferation, hypertrophy and migration. Conversely, inhibiting WNT5A activity in chondrocytes decreased their proliferation, hypertrophy and migration. Blockage of the JNK pathway by its inhibitor, SP600125, impaired these effects of WNT5A on chondrocytes. WNT5A regulated both the expression and transcriptional activity of c-MYC and Cyclin Dl in chondrocytes, both of which were upregulated in condylar cartilage of the rat early TMJ osteoarthritis.Conclusion: WNT5A regulates condylar chondrocyte proliferation, hypertrophy and migration. These findings provide new insights into the role of WNT5A signaling in TMJ cartilage biology and its potential in future therapy for TMJ degenerative diseases.