Netrin-4 Promotes Differentiation and Migration of Osteoblasts

Kwon

et al. 2020

IJMS

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.

Section: Discussionmentioning

confidence: 99%

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

Kwon

et al. 2020

IJMS

“…The recently identified DJ‐1 protein is a novel osteogenic factor that promotes the osteogenesis of MSCs through the activation of FGF signalling. 21 Additionally, recent studies showed that Thy‐1, 22 , 23 netrin 4 24 and retinol‐binding protein 1 25 are positive regulators of osteoblast differentiation. These results indicate that CME contains numerous known osteogenic stimulators or osteogenic regulatory proteins, which might be why CME has osteogenic properties in hMSCs.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive analysis of human chorionic membrane extracts regulating mesenchymal stem cells during osteogenesis

Chae

Song

2021

Cell Proliferation

Objective Human chorionic membrane extracts (CMEs) from placenta are known to be a natural biomaterial for bone regeneration, with their excellent osteogenic efficacy on osteoblasts. However, little is known about the regulatory mechanism involved. Methods and Results We have shown the in vitro and in vivo bone‐forming ability of CME using human osteoblasts and bone defect animal models, suggesting that CME greatly enhances osteogenesis by providing an osteoconductive environment for the osteogenesis of osteoblasts. Proteomic analysis revealed that CME contained several osteogenesis‐related stimulators such as osteopontin, osteomodulin, Thy‐1, netrin 4, retinol‐binding protein and DJ‐1. Additionally, 23 growth factors/growth factor–related proteins were found in CME, which may trigger mitogen‐activated protein kinase (MAPK) signalling as a specific cellular signalling pathway for osteogenic differentiation. Microarray analysis showed four interaction networks (chemokine, Wnt signalling, angiogenesis and ossification), indicating the possibility that CME can promote osteogenic differentiation through a non‐canonical Wnt‐mediated CXCL signalling–dependent pathway. Conclusions The results of this study showed the function and mechanism of action of CME during the osteogenesis of osteoblasts and highlighted a novel strategy for the use of CME as a biocompatible therapeutic material for bone regeneration.

“…More recent data show that, also, Netrin-4 may link angiogenesis and bone remodeling. Endothelial Netrin 4 inhibits osteoclast differentiation in vitro and showed osteoprotective effects in an osteoporotic mouse model [ 36 ], but the effect of Netrin-4 does not seem to be limited to osteoclasts, as Netrin-4-dependent differentiation and migration of osteoblasts were also shown [ 37 ].…”

Section: Bone Remodelingmentioning

confidence: 99%

Neuronal Guidance Molecules in Bone Remodeling and Orthodontic Tooth Movement

Şen

Erber

2022

IJMS

During orthodontic tooth movement, mechanically induced remodeling occurs in the alveolar bone due to the action of orthodontic forces. The number of factors identified to be involved in mechanically induced bone remodeling is growing steadily. With the uncovering of the functions of neuronal guidance molecules (NGMs) for skeletal development as well as for bone homeostasis, NGMs are now also among the potentially significant factors for the regulation of bone remodeling during orthodontic tooth movement. This narrative review attempts to summarize the functions of NGMs in bone homeostasis and provides insight into the currently sparse literature on the functions of these molecules during orthodontic tooth movement. Presently, four families of NGMs are known: Netrins, Slits, Semaphorins, ephrins and Eph receptors. A search of electronic databases revealed roles in bone homeostasis for representatives from all four NGM families. Functions during orthodontic tooth movement, however, were only identified for Semaphorins, ephrins and Eph receptors. For these, crucial prerequisites for participation in the regulation of orthodontically induced bone remodeling, such as expression in cells of the periodontal ligament and in the alveolar bone, as well as mechanical inducibility, were shown, which suggests that the importance of NGMs in orthodontic tooth movement may be underappreciated to date and further research might be warranted.