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Differing calcification processes in cultured vascular smooth muscle cells and osteoblasts

Patel, J J; Bourne, L E; Davies, B K; Arnett, T R; MacRae, V E; Wheeler-Jones, C P D; Orriss, I R


J J Patel

L E Bourne

B K Davies

T R Arnett

V E MacRae

C P D Wheeler-Jones

I R Orriss


Arterial medial calcification (AMC) is the deposition of calcium phosphate mineral, often as hydroxyapatite, in the medial layer of the arteries. AMC shares some similarities to skeletal mineralisation and has been associated with the transdifferentiation of vascular smooth muscle cells (VSMCs) towards an osteoblast-like phenotype. This study used primary mouse VSMCs and calvarial osteoblasts to directly compare the established and widely used in vitro models of AMC and bone formation. Significant differences were identified between osteoblasts and calcifying VSMCs. First, osteoblasts formed large mineralised bone nodules that were associated with widespread deposition of an extracellular collagenous matrix. In contrast, VSMCs formed small discrete regions of calcification that were not associated with collagen deposition and did not resemble bone. Second, calcifying VSMCs displayed a progressive reduction in cell viability over time (≤7-fold), with a 50% increase in apoptosis, whereas osteoblast and control VSMCs viability remained unchanged. Third, osteoblasts expressed high levels of alkaline phosphatase (TNAP) activity and TNAP inhibition reduced bone formation by to 90%. TNAP activity in calcifying VSMCs was ∼100-fold lower than that of bone-forming osteoblasts and cultures treated with β-glycerophosphate, a TNAP substrate, did not calcify. Furthermore, TNAP inhibition had no effect on VSMC calcification. Although, VSMC calcification was associated with increased mRNA expression of osteoblast-related genes (e.g. Runx2, osterix, osteocalcin, osteopontin), the relative expression of these genes was up to 40-fold lower in calcifying VSMCs versus bone-forming osteoblasts. In summary, calcifying VSMCs in vitro display some limited osteoblast-like characteristics but also differ in several key respects: 1) their inability to form collagen-containing bone; 2) their lack of reliance on TNAP to promote mineral deposition; and, 3) the deleterious effect of calcification on their viability.


Patel, J. J., Bourne, L. E., Davies, B. K., Arnett, T. R., MacRae, V. E., Wheeler-Jones, C. P. D., & Orriss, I. R. (2019). Differing calcification processes in cultured vascular smooth muscle cells and osteoblasts. Experimental Cell Research, 380(1), 100-113.

Journal Article Type Article
Acceptance Date Apr 15, 2019
Publication Date Jul 1, 2019
Deposit Date Apr 25, 2019
Publicly Available Date May 31, 2019
Journal Experimental Cell Research
Print ISSN 0014-4827
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 380
Issue 1
Pages 100-113
Public URL


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