Caveolin-1 regulates proliferation and osteogenic differentiation of human mesenchymal stem cells.
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.
Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Bethesda, MD 20892, USA.
Natasha
N
Baker
Guofeng
G
Zhang
Yang
Y
You
Rocky S
RS
Tuan
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000880:Anthraquinones; D001853:Bone Marrow / Q000378:metabolism; D021941:Caveolae / Q000648:ultrastructure; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D003470:Culture Media / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008856:Microscopy, Fluorescence; D010012:Osteogenesis; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection
D000880:Anthraquinones; C495540:CAV1 protein, human; D051242:Caveolin 1; D003470:Culture Media; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C010078:alizarin; D000469:Alkaline Phosphatase