VEGF promotes cartilage angiogenesis by phospho-ERK1/2 activation of Dll4 signaling in temporomandibular joint osteoarthritis caused by chronic sleep disturbance in Wistar rats.
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.
School of Stomatology, Shandong University, Jinan City 250012, Shandong Province, China.|Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan City 250012, Shandong Province, China.
Yabing
Y
Dong
Department of Stomatology, Jinan Military General Hospital, Jinan City 250031, Shandong Province, China.
Gaoyi
G
Wu
School of Stomatology, Shandong University, Jinan City 250012, Shandong Province, China.|Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan City 250012, Shandong Province, China.
Ting
T
Zhu
School of Stomatology, Shandong University, Jinan City 250012, Shandong Province, China.|Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan City 250012, Shandong Province, China.
Hongyu
H
Chen
School of Stomatology, Shandong University, Jinan City 250012, Shandong Province, China.|Shandong Provincial Key Laboratory of Oral Tissue Regeneration, Jinan City 250012, Shandong Province, China.
Yong
Y
Zhu
Department of Stomatology, Jinan Military General Hospital, Jinan City 250031, Shandong Province, China.
Guoxiong
G
Zhu
Center for Stem Cells and Regenerative Medicine, The Affiliated Liaocheng Hospital, Taishan Medical University, 252000, Shandong Province, China.
Fabin
F
Han
School of Stomatology, Shandong University, Jinan City 250012, Shandong Province, China.
Huaqiang
H
Zhao
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D002356:Cartilage / Q000098:blood supply*; D003345:Corticosterone / Q000097:blood; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology; D008335:Mandibular Condyle / Q000473:pathology; D008565:Membrane Proteins / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D010003:Osteoarthritis / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012893:Sleep Wake Disorders / Q000473:pathology*; D013704:Temporomandibular Joint / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D042461:Vascular Endothelial Growth Factor A; C064045:delta protein; C467498:vascular endothelial growth factor A, rat; D000324:Adrenocorticotropic Hormone; D048049:Extracellular Signal-Regulated MAP Kinases; D003345:Corticosterone
TMJ-OA; VEGF; angiogenesis; chronic sleep disturbance