In vitro osteoinductive effects of hydroxycholesterol on human adipose-derived stem cells are mediated through the hedgehog signaling pathway

Anisa Yalom, Akishige Hokugo, Sarah Sorice, Andrew Li, Luis A. Segovia Aguilar, Patricia Zuk, Reza Jarrahy

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Human adipose-derived stem cells have been identified as a potential source of cells for use in bone tissue engineering because of their ready availability, ease of harvest, and susceptibility to osteogenic induction. The authors have previously demonstrated the ability of an osteogenic molecule called hydroxycholesterol, an oxidative derivative of cholesterol, to induce osteogenic differentiation in pluripotent murine and rabbit bone marrow stromal cells. In this study, the authors examine the ability of hydroxycholesterol to induce osteogenesis in human adipose-derived stem cells. Methods: Human adipose-derived stem cells were isolated from raw human lipoaspirates through standard isolation and expansion of the stromal vascular fraction. Cells were plated onto tissue culture plates in control medium and harvested between passages 2 and 3, incubated with conventional osteogenic media, and treated with various concentrations (1, 5, and 10 μM) of the 20(S) analogue of hydroxycholesterol. Evaluation of cellular osteogenic activity was performed. The role of the hedgehog signaling pathway in hydroxycholesterolmediated osteogenesis was evaluated by hedgehog inhibition assays. Results: Alkaline phosphatase activity, bone-related gene expression, and mineralization were all significantly increased in cultures of human adipose-derived stem cells treated with 5 μM of 20(S)-hydroxycholesterol relative to controls. In addition, induction of hydroxycholesterol-mediated osteogenesis was mitigated by the addition of the hedgehog pathway inhibitor to cell cultures, implicating the hedgehog signaling pathway in the osteogenic mechanism on human adipose-derived stem cells by hydroxycholesterol. Conclusion: These in vitro studies demonstrate that hydroxycholesterol exerts an osteoinductive influence on human adipose-derived stem cells and that these effects are mediated at least in part through the hedgehog signaling pathway.

Original languageEnglish (US)
Pages (from-to)960-968
Number of pages9
JournalPlastic and reconstructive surgery
Volume134
Issue number5
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

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Hydroxycholesterols
Hedgehogs
Stem Cells
Osteogenesis
Bone and Bones
Tissue Engineering
In Vitro Techniques
Mesenchymal Stromal Cells
Alkaline Phosphatase
Blood Vessels
Cell Culture Techniques
Cholesterol
Rabbits
Gene Expression

ASJC Scopus subject areas

  • Surgery

Cite this

In vitro osteoinductive effects of hydroxycholesterol on human adipose-derived stem cells are mediated through the hedgehog signaling pathway. / Yalom, Anisa; Hokugo, Akishige; Sorice, Sarah; Li, Andrew; Segovia Aguilar, Luis A.; Zuk, Patricia; Jarrahy, Reza.

In: Plastic and reconstructive surgery, Vol. 134, No. 5, 01.01.2014, p. 960-968.

Research output: Contribution to journalArticle

Yalom, Anisa ; Hokugo, Akishige ; Sorice, Sarah ; Li, Andrew ; Segovia Aguilar, Luis A. ; Zuk, Patricia ; Jarrahy, Reza. / In vitro osteoinductive effects of hydroxycholesterol on human adipose-derived stem cells are mediated through the hedgehog signaling pathway. In: Plastic and reconstructive surgery. 2014 ; Vol. 134, No. 5. pp. 960-968.
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abstract = "Background: Human adipose-derived stem cells have been identified as a potential source of cells for use in bone tissue engineering because of their ready availability, ease of harvest, and susceptibility to osteogenic induction. The authors have previously demonstrated the ability of an osteogenic molecule called hydroxycholesterol, an oxidative derivative of cholesterol, to induce osteogenic differentiation in pluripotent murine and rabbit bone marrow stromal cells. In this study, the authors examine the ability of hydroxycholesterol to induce osteogenesis in human adipose-derived stem cells. Methods: Human adipose-derived stem cells were isolated from raw human lipoaspirates through standard isolation and expansion of the stromal vascular fraction. Cells were plated onto tissue culture plates in control medium and harvested between passages 2 and 3, incubated with conventional osteogenic media, and treated with various concentrations (1, 5, and 10 μM) of the 20(S) analogue of hydroxycholesterol. Evaluation of cellular osteogenic activity was performed. The role of the hedgehog signaling pathway in hydroxycholesterolmediated osteogenesis was evaluated by hedgehog inhibition assays. Results: Alkaline phosphatase activity, bone-related gene expression, and mineralization were all significantly increased in cultures of human adipose-derived stem cells treated with 5 μM of 20(S)-hydroxycholesterol relative to controls. In addition, induction of hydroxycholesterol-mediated osteogenesis was mitigated by the addition of the hedgehog pathway inhibitor to cell cultures, implicating the hedgehog signaling pathway in the osteogenic mechanism on human adipose-derived stem cells by hydroxycholesterol. Conclusion: These in vitro studies demonstrate that hydroxycholesterol exerts an osteoinductive influence on human adipose-derived stem cells and that these effects are mediated at least in part through the hedgehog signaling pathway.",
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AU - Sorice, Sarah

AU - Li, Andrew

AU - Segovia Aguilar, Luis A.

AU - Zuk, Patricia

AU - Jarrahy, Reza

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