In vitro study of a novel oxysterol for osteogenic differentiation on rabbit bone marrow stromal cells

Akishige Hokugo, Sarah Sorice, Anisa Yalom, James C. Lee, Andrew Li, Patricia Zuk, Reza Jarrahy

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

BACKGROUND: Bone morphogenetic proteins (BMPs) are powerful osteoinductive growth factors but are associated with exorbitant costs and undesirable side effects. Oxysterols are biocompatible cholesterol oxidation products with osteoinductive properties that may represent an alternative to BMP. In this study, the authors examine the osteogenic potential and mechanisms of actions of oxysterol 49, a novel oxysterol analogue, in primary rabbit bone marrow stromal cells. METHODS: Bone marrow stromal cells were isolated from the iliac crests of New Zealand White rabbits and then treated with various concentrations of oxysterol 49 or BMP-2, either alone or in combination. Alkaline phosphatase activity and expression of osteocalcin and osteopontin were evaluated. The effect of treatment of cells with cyclopamine, a known hedgehog signaling pathway inhibitor, was also assessed. RESULTS: Alkaline phosphatase activity was increased in cells treated with 1 μM oxysterol 49 relative to cells treated with BMP-2. Expression of osteocalcin and osteopontin in cells treated with oxysterol 49 and BMP-2 was equivalent. Alkaline phosphatase activity was decreased with the addition of cyclopamine. Combined treatment with oxysterol 49 and BMP-2 resulted in additive increases in alkaline phosphatase activity and osteocalcin and osteopontin expression. CONCLUSIONS: Oxysterol 49 has osteoinductive properties that are similar to those of BMP-2 in rabbit bone marrow stromal cells. The mechanism of this activity is at least in part related to the hedgehog signaling pathway. The two growth factors demonstrate additive effects when used in combination. Further study is required to examine the potential role of oxysterol 49 as a complement or alternative to BMP-2 in bone tissue engineering.

Original languageEnglish (US)
Pages (from-to)70e-80e
JournalPlastic and reconstructive surgery
Volume132
Issue number1
DOIs
StatePublished - Jul 1 2013
Externally publishedYes

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Mesenchymal Stromal Cells
Bone Morphogenetic Protein 2
Rabbits
Osteopontin
Alkaline Phosphatase
Osteocalcin
Bone Morphogenetic Proteins
Hedgehogs
Intercellular Signaling Peptides and Proteins
In Vitro Techniques
Oxysterols
Tissue Engineering
Action Potentials
Cholesterol
Costs and Cost Analysis
Bone and Bones

ASJC Scopus subject areas

  • Surgery

Cite this

In vitro study of a novel oxysterol for osteogenic differentiation on rabbit bone marrow stromal cells. / Hokugo, Akishige; Sorice, Sarah; Yalom, Anisa; Lee, James C.; Li, Andrew; Zuk, Patricia; Jarrahy, Reza.

In: Plastic and reconstructive surgery, Vol. 132, No. 1, 01.07.2013, p. 70e-80e.

Research output: Contribution to journalArticle

Hokugo, Akishige ; Sorice, Sarah ; Yalom, Anisa ; Lee, James C. ; Li, Andrew ; Zuk, Patricia ; Jarrahy, Reza. / In vitro study of a novel oxysterol for osteogenic differentiation on rabbit bone marrow stromal cells. In: Plastic and reconstructive surgery. 2013 ; Vol. 132, No. 1. pp. 70e-80e.
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AU - Zuk, Patricia

AU - Jarrahy, Reza

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N2 - BACKGROUND: Bone morphogenetic proteins (BMPs) are powerful osteoinductive growth factors but are associated with exorbitant costs and undesirable side effects. Oxysterols are biocompatible cholesterol oxidation products with osteoinductive properties that may represent an alternative to BMP. In this study, the authors examine the osteogenic potential and mechanisms of actions of oxysterol 49, a novel oxysterol analogue, in primary rabbit bone marrow stromal cells. METHODS: Bone marrow stromal cells were isolated from the iliac crests of New Zealand White rabbits and then treated with various concentrations of oxysterol 49 or BMP-2, either alone or in combination. Alkaline phosphatase activity and expression of osteocalcin and osteopontin were evaluated. The effect of treatment of cells with cyclopamine, a known hedgehog signaling pathway inhibitor, was also assessed. RESULTS: Alkaline phosphatase activity was increased in cells treated with 1 μM oxysterol 49 relative to cells treated with BMP-2. Expression of osteocalcin and osteopontin in cells treated with oxysterol 49 and BMP-2 was equivalent. Alkaline phosphatase activity was decreased with the addition of cyclopamine. Combined treatment with oxysterol 49 and BMP-2 resulted in additive increases in alkaline phosphatase activity and osteocalcin and osteopontin expression. CONCLUSIONS: Oxysterol 49 has osteoinductive properties that are similar to those of BMP-2 in rabbit bone marrow stromal cells. The mechanism of this activity is at least in part related to the hedgehog signaling pathway. The two growth factors demonstrate additive effects when used in combination. Further study is required to examine the potential role of oxysterol 49 as a complement or alternative to BMP-2 in bone tissue engineering.

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