Oxy133, a novel osteogenic agent, promotes bone regeneration in an intramembranous bone-healing model

Andrew Li, Akishige Hokugo, Luis Andres Segovia, Anisa Yalom, Kameron Rezzadeh, Situo Zhou, Zheyu Zhang, Farhad Parhami, Frank Stappenbeck, Reza Jarrahy

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Current reconstructive techniques for complex craniofacial osseous defects are challenging and are associated with significant morbidity. Oxysterols are naturally occurring cholesterol oxidation products with osteogenic potential. In this study, we investigated the effects of a novel semi-synthetic oxysterol, Oxy133, on in vitro osteogenesis and an in vivo intramembranous bone-healing model. Rabbit bone marrow stromal cells (BMSCs) were treated with either Oxy133 or BMP-2. Alkaline phosphatase (ALP) activity, expression of osteogenic gene markers and in vitro mineralization were all examined. Next, collagen sponges carrying either Oxy133 or BMP-2 were used to reconstruct critical-sized cranial defects in mature rabbits and bone regeneration was assessed. To determine the mechanism of action of Oxy133 both in vitro and in vivo, rabbit BMSCs cultures and collagen sponge/Oxy133 implants were treated with the Hedgehog signalling pathway inhibitor, cyclopamine, and similar outcomes were measured. ALP activity in rabbit BMSCs treated with 1 μm Oxy133 was induced and was significantly higher than in control cells. These results were mitigated in cultures treated with cyclopamine. Expression of osteogenic gene markers and mineralization in BMSCs treated with 1 μm Oxy133 was significantly higher than in control groups. Complete bone regeneration was noted in vivo when cranial defects were treated with Oxy133; healing was incomplete, however, when cyclopamine was added. Collectively, these results demonstrate that Oxy133 has the ability to induce osteogenic differentiation in vitro in rabbit BMSCs and to promote robust bone regeneration in vivo in an animal model of intramembranous bone healing.

Original languageEnglish (US)
Pages (from-to)1490-1499
Number of pages10
JournalJournal of Tissue Engineering and Regenerative Medicine
Volume11
Issue number5
DOIs
StatePublished - May 2017
Externally publishedYes

Keywords

  • bone regeneration
  • Hedgehog signalling
  • intramembranous bone healing
  • osteogenesis
  • oxysterol
  • rabbit

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Biomaterials
  • Biomedical Engineering

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    Li, A., Hokugo, A., Segovia, L. A., Yalom, A., Rezzadeh, K., Zhou, S., Zhang, Z., Parhami, F., Stappenbeck, F., & Jarrahy, R. (2017). Oxy133, a novel osteogenic agent, promotes bone regeneration in an intramembranous bone-healing model. Journal of Tissue Engineering and Regenerative Medicine, 11(5), 1490-1499. https://doi.org/10.1002/term.2047