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Cyclic strain inhibits switching of smooth muscle cells to an osteoblast‐like phenotype
Author(s) -
Nikolovski Janeta,
Kim ByungSoo,
Mooney David J.
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0459fje
Subject(s) - osteopontin , ectopic calcification , phenotype , osteoblast , calcification , microbiology and biotechnology , gene expression , alkaline phosphatase , biology , runx2 , matrix gla protein , ectopic expression , gene , in vivo , chemistry , in vitro , pathology , endocrinology , genetics , biochemistry , medicine , enzyme
Ectopic calcification is commonly associated with cardiovascular disease, injury, aging, and biomaterial implantation. We hypothesized that the normal mechanical environment of smooth muscle cells (SMCs) inhibits a phenotypic switch to a pattern of gene expression more typical for bone and inducive for calcification. This hypothesis was tested using a 3‐D engineered smooth muscle tissue model subjected to cyclic mechanical strain. This simplified model maintained a 3‐D tissue architecture while eliminating systemic effects as can be seen with in vivo models. All engineered tissues were found to express bone‐associated genes (osteopontin, matrix gla protein, alkaline phosphatase, and the transcription factor CBFA‐1). Strikingly, however, expression of these genes was down‐regulated in tissues exposed to cyclic strain at all time points ranging from 5 to 150 days. Furthermore, long‐term strain played a protective role in regard to calcification, as unstrained tissues exhibited increased calcium deposition with respect to strained tissues. The results of this study suggest that without an appropriate mechanical environment, SMCs in 3‐D culture undergo a phenotypic conversion to an osteoblast‐like pattern of gene expression. This finding has significant implications for the mechanisms underlying a variety of cardiovascular diseases and indicates the broad utility of engineered tissue models in basic biology studies.