BMP9/COX-2 axial mediates high phosphate-induced calcification in vascular smooth muscle cells via Wnt/β-catenin pathway
Authors: Zhong-Liang Deng
Han Wang
Wen-Yan Ren
Yun-Peng Liao
Yu-Xi Su
Bai-Cheng He
Jia-Hui Zhu
Jin Cui
Fang He
Hua Gan
Yan Ma
Journal: Journal of Cellular Biochemistry (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: BMP9; COX-2; Wnt/β-catenin; high phosphate; vascular calcification.
Affiliations: Department of Nephrology, First Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China., Key Laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing Medical University, Chongqing, People's Republic of China., Department of Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China., Infectious Disease Laboratory of Chongqing Medical University, Chongqing, People's Republic of China., Department of Orthorpedic, Second Affiliated Hospital, Chongqing Medical University, Chongqing, People's Republic of China., Department of Orthorpedic, Children Hospital of Chongqing Medical University, Chongqing, People's Republic of China.

Abstract:  Vascular calcification is a notable risk factor for cardiovascular system. High phosphate can induce calcification in vascular smooth muscle cells (VSMCs), but the detail mechanism underlying this process remains unclear. In the present study, we determined the relationship between high phosphate and bone morphogenetic protein 9 (BMP9) in VSMCs, the effect of BMP9 on calcification in VSMCs and the effect of COX-2 on BMP9 induced calcification in VSMCs, as well as the possible mechanism underlying this biological process. We found that high phosphate obviously up-regulates the expression of BMP9 in VSMCs. Over-expression of BMP9 decreases the level of alpha-smooth muscle cell actin (α-SMA) apparently, but increases the level of Runx-2, Dlx-5, and ALP in VSMCs. Meanwhile, BMP9 increases the level of OPN and OCN, promotes mineralization in VSMCs and induces calcification in thoracic aorta. High phosphate and over-expression of BMP9 increases the level of COX-2. Over-expression of COX-2 enhances the inhibitory effect of BMP9 on α-SAM and increases the level of OPN and OCN induced by BMP9. However, inhibition of COX-2 decreases the BMP9-induced calcification in VSMCs and thoracic aorta. For mechanism, we found that high phosphate or BMP9 increases the level of β-catenin and p-GSK3β in VSMCs, but no substantial effect on GSK3β. However, COX-2 inhibitor decreases the expression of β-catenin induced by BMP9. Our findings indicated that BMP9 is involved in the phosphate-induced calcification in VSMCs and COX-2 partly mediates the BMP9-induced calcification in VSMCs through activating Wnt/β-catenin pathway. 

Retracted: No

PubPeer comments:
 Figure 3F. ![file] , 
 Duplication of areas in two panels of Fig 5E ![file] and what looks like the wrong image used for the 2.5mM sample in Fig 1D ![file] , 
 #1 Got this kindly comment, Iu2019ll check all the original data carefully and then make a response to the journal. #2 Got this kindly comment, Iu2019ll check all the original data carefully and then make a response to the journal. , 
 #3 Is a correction in the pipeline? , 
 #4 The editorial process is, perhaps, calcified. , 
 #3 #4 https: onlinelibrary.wiley.com doi full 10.1002 jcb.29185 ,