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 1, 2, * , Gaoyi Wu 3, * , Ting Zhu 1, 2, * , Hongyu Chen 1, 2 , Yong Zhu 1, 2 , Guoxiong Zhu 3 , Fabin Han 4 , Huaqiang Zhao 1 1 School of Stomatology, Shandong University, Wen Hua Xi Lu, Jinan City 250012, Shandong Province, China 2 Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Wen Hua Xi Lu, Jinan City 250012, Shandong Province, China 3 Department of Stomatology, Jinan Military General Hospital, Shi Fan Lu, Jinan City 250031, Shandong Province, China 4 Center 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: zhaohq@sdu.edu.cn Keywords: chronic sleep disturbance, angiogenesis, TMJ-OA, VEGF Received: November 22, 2016      Accepted: January 18, 2017      Published: January 28, 2017 ABSTRACT 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.