Enhancement of Bone Marrow-Derived Mesenchymal Stem Cell Osteogenesis and New Bone Formation in Rats by Obtusilactone A

Int J Mol Sci. 2017 Nov 15;18(11):2422. doi: 10.3390/ijms18112422.

Abstract

The natural pure compound obtusilactone A (OA) was identified in Cinnamomum kotoense Kanehira & Sasaki, and shows effective anti-cancer activity. We studied the effect of OA on osteogenesis of bone marrow-derived mesenchymal stem cells (BMSCs). OA possesses biocompatibility, stimulates Alkaline Phosphatase (ALP) activity and facilitates mineralization of BMSCs. Expression of osteogenesis markers BMP2, Runx2, Collagen I, and Osteocalcin was enhanced in OA-treated BMSCs. An in vivo rat model with local administration of OA via needle implantation to bone marrow-residing BMSCs revealed that OA increased the new bone formation and trabecular bone volume in tibias. Micro-CT images and H&E staining showed more trabecular bone at the needle-implanted site in the OA group than the normal saline group. Thus, OA confers an osteoinductive effect on BMSCs via induction of osteogenic marker gene expression, such as BMP2 and Runx2 expression and subsequently elevates ALP activity and mineralization, followed by enhanced trabecular bone formation in rat tibias. Therefore, OA is a potential osteoinductive drug to stimulate new bone formation by BMSCs.

Keywords: Cinnamomum kotoense; bone formation; bone marrow derived mesenchymal stem cells (BMSCs); obtusilactone A; osteogenesis.

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology*
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Cancellous Bone / diagnostic imaging
  • Cancellous Bone / drug effects
  • Cell Death / drug effects
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics
  • Cinnamomum / chemistry
  • Gene Expression Regulation / drug effects
  • Imaging, Three-Dimensional
  • Lignans / chemistry
  • Lignans / pharmacology*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Mice, Inbred BALB C
  • Osseointegration / drug effects
  • Osseointegration / genetics
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Rats, Sprague-Dawley
  • Tibia / drug effects
  • Tibia / growth & development
  • X-Ray Microtomography

Substances

  • Lignans
  • obtusilactone A