The secreted protein WNT5A regulates condylar chondrocyte proliferation, hypertrophy and migration
| Autor: | Xianpeng Ge, Xu-chen Ma, Ruirui Shi |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Chondrocyte hypertrophy Matrix metalloproteinase Biology Wnt-5a Protein Chondrocyte Muscle hypertrophy Proto-Oncogene Proteins c-myc Rats Sprague-Dawley 03 medical and health sciences Chondrocytes Cyclin D1 stomatognathic system Cell Movement Internal medicine medicine Animals General Dentistry Cell Proliferation Cartilage Mandibular Condyle Wnt signaling pathway Hypertrophy Cell Biology General Medicine Temporomandibular Joint Disorders Rats Up-Regulation Cell biology body regions WNT5A Disease Models Animal 030104 developmental biology Endocrinology medicine.anatomical_structure Otorhinolaryngology embryonic structures sense organs Signal Transduction |
| Zdroj: | Archives of Oral Biology. 82:171-179 |
| ISSN: | 0003-9969 |
| DOI: | 10.1016/j.archoralbio.2017.06.019 |
| Popis: | Objective Our previous study showed that WNT5A, a member of the noncanonical WNT pathway, is involved in interleukin-1beta 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 D1 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 D1 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect