7-HYB, a Phenolic Compound Isolated from Myristica fragrans Houtt Increases Cell Migration, Osteoblast Differentiation, and Mineralization through BMP2 and β-catenin Signaling

Int J Mol Sci. 2020 Oct 29;21(21):8059. doi: 10.3390/ijms21218059.

Abstract

The seeds (nutmegs) of Myristica fragrans Houtt have been used as popular spices and traditional medicine to treat a variety of diseases. A phenolic compound, ((7S)-8'-(benzo[3',4']dioxol-1'-yl)-7-hydroxypropyl)benzene-2,4-diol (7-HYB) was isolated from the seeds of M. fragrans. This study aimed to investigate the anabolic effects of 7-HYB in osteogenesis and bone mineralization. In the present study, 7-HYB promotes the early and late differentiation of MC3T3-E1 preosteoblasts. 7-HYB also elevated cell migration rate during differentiation of the preosteoblasts with the increased phosphorylation of mitogen-activated protein kinases (MAPKs) including ERK1/2, p38, and JNK. In addition, 7-HYB induced the protein level of BMP2, the phosphorylation of Smad1/5/8, and the expression of RUNX2. 7-HYB also inhibited GSK3β and subsequently increased the level of β-catenin. However, in bone marrow macrophages (BMMs), 7-HYB has no biological effects in cell viability, TRAP-positive multinuclear osteoclasts, and gene expression (c-Fos and NF-ATc1) in receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis. Our findings suggest that 7-HYB plays an important role in osteoblast differentiation through the BMP2 and β-catenin signaling pathway. It also indicates that 7-HYB might have a therapeutic effect for the treatment of bone diseases such as osteoporosis and periodontitis.

Keywords: 7-HYB; BMP2; Myristica fragrans Houtt; osteoblast; β-catenin.

MeSH terms

  • Animals
  • Benzene Derivatives / chemistry
  • Benzene Derivatives / isolation & purification
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism*
  • Calcification, Physiologic / drug effects*
  • Cell Differentiation
  • Cell Movement*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Macrophages / pathology
  • Mice
  • Myristica / chemistry*
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteoblasts / pathology*
  • Phenols / chemistry
  • Phenols / isolation & purification
  • Phenols / pharmacology
  • Plant Extracts / pharmacology*
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • Benzene Derivatives
  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • CTNNB1 protein, mouse
  • Phenols
  • Plant Extracts
  • beta Catenin