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Caveolin‐1 regulates proliferation and osteogenic differentiation of human mesenchymal stem cells
Author(s) -
Baker Natasha,
Zhang Guofeng,
You Yang,
Tuan Rocky S.
Publication year - 2012
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.24252
Subject(s) - caveolae , mesenchymal stem cell , microbiology and biotechnology , caveolin 1 , stem cell , biology , caveolin , cellular differentiation , gene knockdown , chemistry , signal transduction , cell culture , biochemistry , gene , genetics
Abstract Caveolin‐1 is a scaffolding protein of cholesterol‐rich caveolae lipid rafts in the plasma membrane. In addition to regulating cholesterol transport, caveolin‐1 has the ability to bind a diverse array of cell signaling molecules and regulate cell signal transduction in caveolae. Currently, there is little known about the role of caveolin‐1 in stem cells. It has been reported that the caveolin‐1 null mouse has an expanded population of cells expressing stem cell markers in the gut, mammary gland, and brain, suggestive of a role for caveolin‐1 in stem cell regulation. The caveolin‐1 null mouse also has increased bone mass and an increased bone formation rate, and its bone marrow‐derived mesenchymal stem cells (MSCs) have enhanced osteogenic potential. However, the role of caveolin‐1 in human MSC osteogenic differentiation remains unexplored. In this study, we have characterized the expression of caveolin‐1 in human bone marrow derived MSCs. We show that caveolin‐1 protein is enriched in density gradient‐fractionated MSC plasma membrane, consisting of ∼100 nm diameter membrane‐bound vesicles, and is distributed in a punctate pattern by immunofluoresence localization. Expression of caveolin‐1 increases in MSCs induced to undergo osteogenic differentiation, and siRNA‐mediated knockdown of caveolin‐1 expression enhances MSC proliferation and osteogenic differentiation. Taken together, these findings suggest that caveolin‐1 normally acts to regulate the differentiation and renewal of MSCs, and increased caveolin‐1 expression during MSC osteogenesis likely acts as a negative feedback to stabilize the cell phenotype. J. Cell. Biochem. 113: 3773–3787, 2012. © 2012 Wiley Periodicals, Inc.