title: Cartilage oligomeric matrix protein inhibits vascular smooth muscle calcification by interacting with bone morphogenetic protein-2.
abstract: BACKGROUND
  Vascular calcification is a significant contributor to cardiovascular morbidity and mortality. We recently reported that cartilage oligomeric matrix protein (COMP) is pivotal for maintaining the homeostasis of vascular smooth muscle cells (VSMCs). Whether COMP affects the process of vascular calcification is unknown.
  
  
  OBJECTIVE
  We aimed to test whether COMP modulates vascular calcification.
  
  
  RESULTS
  VSMC calcification in vitro was induced by calcifying media containing high inorganic phosphate or calcium. In vivo medial vessel calcification was induced in rats by 5/6 nephrectomy with a high-phosphate diet or by periadventitial application of CaCl(2) to the abdominal aorta. COMP protein level was markedly reduced in both calcified VSMCs and arteries. COMP deficiency remarkably exacerbated VSMC calcification, whereas ectopic expression of COMP greatly reduced calcification. Furthermore, COMP knockdown facilitated osteogenic markers expression by VSMCs even in the absence of calcifying media. By contrast, COMP overexpression significantly inhibited high phosphate- or high calcium-induced VSMC osteochondrogenic transition. Induction of osteogenic marker expression by COMP silencing was reversed by a soluble form of bone morphogenetic protein (BMP)-2 receptor IA, which suggests a BMP-2-dependent mechanism. Our data revealed that COMP bound directly to BMP-2 through the C terminus, inhibited BMP-2 receptor binding, and blocked BMP-2 osteogenic signaling, indicating COMP inhibits osteochondrogenic transition of VSMCs at least partially through inhibiting BMP-2.
  
  
  CONCLUSIONS
  Our data strongly suggest that COMP is a novel inhibitor of vascular calcification. The imbalance between the effects of COMP and BMP-2 may provide new insights into the pathophysiology of vascular calcification.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing, People's Republic of China.
authors.forename: Yaoyao
authors.initials: Y
authors.lastname: Du
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Bo
authors.initials: B
authors.lastname: Liu
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Tian
authors.forename: Chuan-ju
authors.initials: CJ
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Qingbo
authors.initials: Q
authors.lastname: Xu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Oldberg
authors.initials: O
authors.lastname: Ake
authors.forename: Yongfen
authors.initials: Y
authors.lastname: Qi
authors.forename: Chaochu
authors.initials: C
authors.lastname: Tang
authors.forename: Wei
authors.initials: W
authors.lastname: Kong
authors.forename: Xian
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000378:metabolism / Q000502:physiology*; D002114:Calcinosis / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D002358:Cartilage, Articular / Q000098:blood supply / Q000378:metabolism / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000172:deficiency / Q000378:metabolism*; D055785:Gene Knockdown Techniques / Q000379:methods; D006023:Glycoproteins / Q000172:deficiency / Q000378:metabolism*; D008297:Male; D064235:Matrilin Proteins; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D055396:Bone Morphogenetic Protein 2; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D064235:Matrilin Proteins