Calcifying vascular smooth muscle cells and osteoblasts: independent cell types exhibiting extracellular matrix and biomineralization-related mimicries.
BACKGROUND
Ectopic vascular calcifications represent a major clinical problem associated with cardiovascular disease and mortality. However, the mechanisms underlying pathological vascular calcifications are largely unknown hampering the development of therapies to tackle this life threatening medical condition.


RESULTS
In order to gain insight into the genes and mechanisms driving this pathological calcification process we analyzed the transcriptional profile of calcifying vascular smooth muscle cells (C-VSMCs). These profiles were compared to differentiating osteoblasts, cells that constitute their physiological calcification counterparts in the body. Overall the transcriptional program of C-VSMC and osteoblasts did not overlap. Several genes, some of them relevant for bone formation, were distinctly modulated by C-VSMCs which did not necessarily lose their smooth muscle cell markers while calcifying. Bioinformatics gene clustering and correlation analysis disclosed limited bone-related mechanisms being shared by two cell types. Extracellular matrix (ECM) and biomineralization genes represented common denominators between pathological vascular and physiological bone calcifications. These genes constitute the strongest link between these cells and represent potential drivers for their shared end-point phenotype.


CONCLUSIONS
The analyses support the hypothesis that VSMC trans-differentiate into C-VSMCs keeping their own identity while using mechanisms that osteoblasts use to mineralize. The data provide novel insights into groups of genes and biological processes shared in MSC and VSMC osteogenic differentiation. The distinct gene regulation between C-VSMC and osteoblasts might hold clues to find cell-specific pathway modulations, opening the possibility to tackle undesired vascular calcifications without disturbing physiologic bone formation and vice versa.
Rodrigo D A M
RD
Alves
Marco
M
Eijken
Jeroen
J
van de Peppel
Department of Internal Medicine, Erasmus MC, Wytemaweg 80, 3015 CN Rotterdam, The Netherlands. j.vanleeuwen@erasmusmc.nl.
Johannes P T M
JP
van Leeuwen
D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation; D016000:Cluster Analysis; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D063990:Gene Ontology; D006801:Humans; D008903:Minerals / Q000378:metabolism*; D018716:Molecular Mimicry; D058977:Molecular Sequence Annotation; D009119:Muscle Contraction / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics; D025341:Principal Component Analysis; D015203:Reproducibility of Results; D061205:Vascular Calcification / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers; D008903:Minerals; D000469:Alkaline Phosphatase