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

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.

Biological Mechanisms of Paeonoside in the Differentiation of Pre-Osteoblasts and the Formation of Mineralized Nodules

“…Therefore, research targeting osteoblasts is necessary for the development of anabolic drugs [18,25,26]. Recently, our group demonstrated the biological activities and mechanisms of natural compounds in osteoblasts [27][28][29][30][31]. In the present study, we demonstrated the novel function of PASI isolated from P. suffruticosa in pre-osteoblasts.…”

Paeonolide as a Novel Regulator of Core-Binding Factor Subunit Alpha-1 in Bone-Forming Cells

“…Immunofluorescence was performed as previously described [ 49 ]. Cells were fixed for 10 min at room temperature, permeabilized with 0.2% Triton X-100 in 1× PBS for 20 min, and blocked with 3% BSA diluted in 1× PBS for 1 h. The cells were incubated with anti-RUNX2 primary antibody (1:200, Cell Signaling Technology, Beverly, MA, USA) overnight at 4 °C.…”

Limonoid Triterpene, Obacunone Increases Runt-Related Transcription Factor 2 to Promote Osteoblast Differentiation and Function

“…Immunofluorescence was performed as previously described [ 53 ]. Cells were fixed, permeabilized, and blocked with 3% BSA diluted in 1 × PBS for 1 h. The cells were incubated with an anti-RUNX2 antibody (1:200, Cell Signaling Technology, Beverly, MA, USA) overnight at 4 °C.…”

“…Immunofluorescence was performed as previously described [53]. Cells were fixed, permeabilized, and blocked with 3% BSA diluted in 1 × PBS for 1 h. The cells were incubated with an anti-RUNX2 antibody (1:200, Cell Signaling Technology, Beverly, MA, USA) overnight at 4 • C. After washing three times in 1 × PBS, the cells were incubated with an Alexa-Fluor 568-conjugated secondary antibody (1:500, Invitrogen, Carlsbad, CA, USA) for 2 h at room temperature, stained with DAPI (Sigma-Aldrich, St. Louis, MO, USA), washed three times, mounted on glass slides, and observed using a confocal microscope (K1-Fluo Confocal Laser Scanning Microscope, Korea).…”