Research Papers:

VEGF promotes cartilage angiogenesis by phospho-ERK1/2 activation of Dll4 signaling in temporomandibular joint osteoarthritis caused by chronic sleep disturbance in Wistar rats

Yabing Dong, Gaoyi Wu, Ting Zhu, Hongyu Chen, Yong Zhu, Guoxiong Zhu, Fabin Han and Huaqiang Zhao _

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Oncotarget. 2017; 8:17849-17861. https://doi.org/10.18632/oncotarget.14874

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Yabing Dong1,2,*, Gaoyi Wu3,*, Ting Zhu1,2,*, Hongyu Chen1,2, Yong Zhu1,2, Guoxiong Zhu3, Fabin Han4, Huaqiang Zhao1

1School of Stomatology, Shandong University, Wen Hua Xi Lu, Jinan City 250012, Shandong Province, China

2Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Wen Hua Xi Lu, Jinan City 250012, Shandong Province, China

3Department of Stomatology, Jinan Military General Hospital, Shi Fan Lu, Jinan City 250031, Shandong Province, China

4Center for Stem Cells and Regenerative Medicine, The Affiliated Liaocheng Hospital, Taishan Medical University, 252000, Shandong Province, China

*These authors contributed equally to this work

Correspondence to:

Huaqiang Zhao, email: [email protected]

Keywords: chronic sleep disturbance, angiogenesis, TMJ-OA, VEGF

Received: November 22, 2016     Accepted: January 18, 2017     Published: January 28, 2017


Chronic sleep disturbance (CSD) has been linked to the development of temporomandibular joint osteoarthritis (TMJ-OA). While the pathogenesis of TMJ-OA is unclear, recent studies indicate that osteochondral angiogenesis is important. We developed a rat model of CSD induced TMJ-OA to investigate the changes caused by sleep disturbance and to correlate them with vascular invasion in the TMJ. We found pathological alterations and an increased microvessel density in the rat TMJ following CSD. VEGF, Dll4 and p-ERK1/2, the expression of angiogenic factors, were highly expressed in the rat mandibular condylar cartilage and their expression increased with CSD. Furthermore, we show that VEGF-induce activation of ERK1/2, which in turn, increases Dll4 expression. Together, our results suggest that CSD can cause OA-like pathological alterations in the rat TMJ by increasing angiogenesis.

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