scholarly journals Biological Effects of Anti-RANKL Antibody and Zoledronic Acid on Growth and Tooth Eruption in Growing Mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Motoki Isawa ◽  
Akiko Karakawa ◽  
Nobuhiro Sakai ◽  
Saki Nishina ◽  
Miku Kuritani ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Osteoblast Differentiation ◽  
Pediatric Patients ◽  
Root Formation ◽  
Biological Effects ◽  
Normal Growth ◽  
Bone Diseases ◽  
Bone Volume ◽  
Tooth Eruption ◽  
Tooth Root

AbstractThe anti-bone resorptive drugs denosumab, an anti-human-RANKL antibody, and zoledronic acid (ZOL), a nitrogen-containing bisphosphonate, have recently been applied for treatment of pediatric patients with bone diseases, though details regarding their effects in growing children have yet to be fully elucidated. In the present study, we administered these anti-resorptive drugs to mice from the age of 1 week and continued once-weekly injections for a total of 7 times. Mice that received the anti-RANKL antibody displayed normal growth and tooth eruption, though osteopetrotic bone volume gain in long and alveolar bones was noted, while there were nearly no osteoclasts and a normal of number osteoblasts observed. In contrast, ZOL significantly delayed body growth, tooth root formation, and tooth eruption, with increased osteoclast and decreased osteoblast numbers. These findings suggest regulation of tooth eruption via osteoblast differentiation by some types of anti-resorptive drugs.

Osteogenic Effects of Triterpene Saponin Soyasapogenol B on Differentiation, Mineralization, Autophagy, and Necroptosis

2021 ◽  
Author(s):  
Kyung-Ran Park ◽  
Joon Yeop Lee ◽  
Soo Hyun Kim ◽  
Il Keun Kwon ◽  
Hyung-Mun Yun
Keyword(s):  
Cell Proliferation ◽  
Osteoblast Differentiation ◽  
Biological Effects ◽  
Bone Diseases ◽  
Adhesion Assay ◽  
Pharmacological Properties ◽  
Alizarin Red ◽  
Triterpenoid Saponins ◽  
Triterpene Saponin ◽  
Osteogenic Activity

Abstract Background: Triterpenoid saponins are a diverse group of natural compounds in plants. A triterpene saponin, Soyasapogenol B (SoyB), from Arachis hypogaea (peanut) has various pharmacological properties. This study aimed to elucidate pharmacological properties and mechanisms of SoyB on bone-forming cells. Methods: Cell viability adhesion, and migration were analyzed using MTT assay, cell adhesion assay, and Boyden chamber assay. Osteogenic activity and osteogenicity were analyzed using alkaline phosphatase (ALP) staining and activity, and Alizarin Red S (ARS) staining. Cell signaling, protein expression, and autophagy were analyzed using Western blot analysis, immunofluorescence assay, and DAPGreen autophagy detection assay. Results and Conclusion: In the present study, SoyB (> 99.99% purity), triterpene saponin, was isolated from the fruit of A. hypogaea. At concentrations ranging from 1 to 20 mM, SoyB showed no cell proliferation effects, whereas 30 - 100 mM SoyB increased cell proliferation in MC3T3-E1 cells. Next, osteoblast differentiation was analyzed and found that SoyB enhanced ALP staining and activity and bone mineralization as evidence for early and late osteoblast differentiation. SoyB also induced RUNX2 expression in nucleus with the increased phosphorylation of Smad1/5/8 and JNK2 during osteoblast differentiation. In addition, SoyB-mediated osteoblast differentiation was not associated with autophagy and necroptosis. Furthermore, SoyB increased cell migration and adhesion with the upregulation of MMP13 levels during osteoblast differentiation. The findings of this study provide new evidence that SoyB possesses biological effects on osteogenic activity and osteogenicity in bone-forming cells, and suggest a potentially beneficial role for peanuts foods and drugs containing SoyB in the treatment and prevention of bone diseases.

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

2020 ◽  
Vol 21 (21) ◽  
pp. 8059
Author(s):  
Kyung-Ran Park ◽  
Yoon-Ju Kwon ◽  
Ji-Eun Park ◽  
Hyung-Mun Yun
Keyword(s):  
Cell Migration ◽  
Phenolic Compound ◽  
Osteoblast Differentiation ◽  
Bone Mineralization ◽  
Biological Effects ◽  
Bone Diseases ◽  
Myristica Fragrans ◽  
Receptor Activator ◽  
Mitogen Activated Protein ◽  
Myristica Fragrans Houtt

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.

scholarly journals The Role of Wnt Signaling in Postnatal Tooth Root Development

2021 ◽  
Vol 2 ◽  
Author(s):  
Nicha Tokavanich ◽  
Marc N. Wein ◽  
Jeryl D. English ◽  
Noriaki Ono ◽  
Wanida Ono
Keyword(s):  
Transcription Factors ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Root Development ◽  
Root Formation ◽  
Wnt Signaling Pathway ◽  
Tooth Eruption ◽  
Follicle Cells ◽  
Tooth Root

Appropriate tooth root formation and tooth eruption are critical for achieving and maintaining good oral health and quality of life. Tooth eruption is the process through which teeth emerge from their intraosseous position to their functional position in the oral cavity. This temporospatial process occurs simultaneously with tooth root formation through a cascade of interactions between the epithelial and adjoining mesenchymal cells. Here, we will review the role of the Wnt system in postnatal tooth root development. This signaling pathway orchestrates the process of tooth root formation and tooth eruption in conjunction with several other major signaling pathways. The Wnt signaling pathway is comprised of the canonical, or Wnt/β-catenin, and the non-Canonical signaling pathway. The expression of multiple Wnt ligands and their downstream transcription factors including β-catenin is found in the cells in the epithelia and mesenchyme starting from the initiation stage of tooth development. The inhibition of canonical Wnt signaling in an early stage arrests odontogenesis. Wnt transcription factors continue to be present in dental follicle cells, the progenitor cells responsible for differentiation into cells constituting the tooth root and the periodontal tissue apparatus. This expression occurs concurrently with osteogenesis and cementogenesis. The conditional ablation of β-catenin in osteoblast and odontoblast causes the malformation of the root dentin and cementum. On the contrary, the overexpression of β-catenin led to shorter molar roots with thin and hypo-mineralized dentin, along with the failure of tooth eruption. Therefore, the proper expression of Wnt signaling during dental development is crucial for regulating the proliferation, differentiation, as well as epithelial-mesenchymal interaction essential for tooth root formation and tooth eruption.

scholarly journals Mesenchymal Progenitor Regulation of Tooth Eruption: A View from PTHrP

2019 ◽  
Vol 99 (2) ◽  
pp. 133-142 ◽  
Author(s):  
M. Nagata ◽  
N. Ono ◽  
W. Ono
Keyword(s):  
Parathyroid Hormone ◽  
Progenitor Cell ◽  
Root Formation ◽  
Genetic Disorder ◽  
Tooth Eruption ◽  
Cell Populations ◽  
Mesenchymal Progenitor Cell ◽  
Tooth Root ◽  
Parathyroid Hormone Related Protein ◽  
Periodontal Attachment

Tooth eruption is a unique biological process by which highly mineralized tissues emerge into the outer world, and it occurs concomitantly with tooth root formation. These 2 processes have been considered independent phenomena; however, recent studies support the theory that they are indeed intertwined. Dental mesenchymal progenitor cells in the dental follicle lie at the heart of the coupling of these 2 processes, providing a source for diverse mesenchymal cells that support formation of the highly functional tooth root and the periodontal attachment apparatus, while facilitating formation of osteoclasts. These cells are regulated by autocrine signaling by parathyroid hormone–related protein (PTHrP) and its parathyroid hormone/PTHrP receptor PPR. This PTHrP-PPR signaling appears to crosstalk with other signaling pathways and regulates proper cell fates of mesenchymal progenitor cell populations. Disruption of this autocrine PTHrP-PPR signaling in these cells leads to defective formation of the periodontal attachment apparatus, tooth root malformation, and failure of tooth eruption in molars, which essentially recapitulate primary failure of eruption in humans, a rare genetic disorder exclusively affecting tooth eruption. Diversity and distinct functionality of these mesenchymal progenitor cell populations that regulate tooth eruption and tooth root formation are beginning to be unraveled.

scholarly journals TMARg, a Novel Anthraquinone Isolated from Rubia cordifolia Nakai, Increases Osteogenesis and Mineralization through BMP2 and β-Catenin Signaling

2020 ◽  
Vol 21 (15) ◽  
pp. 5332
Author(s):  
Kyung-Ran Park ◽  
Joon Yeop Lee ◽  
Bo-Mi Kim ◽  
Sang Wook Kang ◽  
Hyung-Mun Yun
Keyword(s):  
Cell Migration ◽  
Signaling Pathways ◽  
Intracellular Signaling ◽  
Osteoblast Differentiation ◽  
Biological Effects ◽  
Bone Diseases ◽  
C2c12 Cells ◽  
Alizarin Red ◽  
Rubia Cordifolia ◽  
Mitogen Activated Protein

Background: Plant extracts have long been regarded as useful medicines in the treatment of human diseases. Rubia cordifolia Nakai has been used as a traditional medicine, as it has pharmacological properties such as antioxidant and anti-inflammatory activity. However, the biological functions of TMARg, isolated from the roots of R. cordifolia, in osteoblast differentiation remain unknown. This study was performed to investigate the pharmacological effects and intracellular signaling of TMARg in the osteoblast differentiation of pre-osteoblast MC3T3-E1 cells and mesenchymal precursor C2C12 cells. Methods: Cell viability was evaluated using an MTT assay. Early and late osteoblast differentiation was examined by analyzing the activity of alkaline phosphatase (ALP), and by staining it with Alizarin red S (ARS). Cell migration was determined by using migration assays. Western blot analysis and immunocytochemical analysis were used to examine the intracellular signaling pathways and differentiation proteins. Results: In the present study, TMARg showed no cytotoxicity and increased the osteoblast differentiation in pre-osteoblasts, as assessed from the alkaline phosphate (ALP) staining and activity and ARS staining. TMARg also induced BMP2 expression and increased the p-smad1/5/8-RUNX2 and β-catenin pathways in both MC3T3-E1 and C2C12 cells. Furthermore, TMARg activated mitogen-activated protein kinases (MAPKs) and increased the cell migration rate. In addition, the TMARg-mediated osteoblast differentiation was suppressed by BMP and Wnt inhibitors with the downregulation of BMP2 expression. Conclusion: These findings demonstrate that TMARg exerts pharmacological and biological effects on osteoblast differentiation through the activation of BMP2 and β-catenin signaling pathways, and suggest that TMARg might be a potential phytomedicine for the treatment of bone diseases.

scholarly journals Skeletal Site-Specific Response of Jawbones and Long Bones to Surgical Interventions in Rats Treated with Zoledronic Acid

2019 ◽  
Vol 2019 ◽  
pp. 1-11
Author(s):  
Jing Yi Wang ◽  
Lei Huo ◽  
Ru Qing Yu ◽  
Nian Jing Rao ◽  
Weijia William Lu ◽  
...  
Keyword(s):  
Zoledronic Acid ◽  
Surgical Procedures ◽  
Bone Diseases ◽  
Bone Volume ◽  
Female Rats ◽  
Specific Response ◽  
Long Bones ◽  
Mineral Density ◽  
Bone Response ◽  
Skeletal Site

Bisphosphonates (BPs) have been extensively used for management of bone diseases with pathologically high resorption. Despite the great clinical benefits, a severe complication known as medication-related osteonecrosis of the jaw (MRONJ) has been reported. It is found that most of the reported MRONJ cases were limited in the jawbones/craniofacial bones instead of long bones. The present study aims to investigate the differential bone response to surgical procedures between jawbones and long bones exposed to BPs. Forty-eight skeletal mature Sprague Dawley female rats were administered oncologic dose of zoledronic acid (ZA) or normal saline for 4 weeks and then subjected to tooth extraction on the mandible and maxilla, and a bone defect creation on the femur. After surgical procedures, ZA or saline treatment were continued until sacrifice at week 2, week 4, and week 8, post-operatively. The samples were subjected to micro-computerized tomography (micro-CT) and histological assessment. Osteonecrosis was only found in jawbones in ZA-treated rats. ZA-treated rats showed significantly higher bone mineral density with greater bone volume in all surgical sites than that in the controls. The length of exposure of ZA did not seem to affect trabecular microstructure, and it only showed higher bone volume and BMD with longer healing time which is expected in the healing process.

scholarly journals Multiple essential MT1-MMP functions in tooth root formation, dentinogenesis, and tooth eruption

2016 ◽  
Vol 52-54 ◽  
pp. 266-283 ◽  
Author(s):  
H. Xu ◽  
T.N. Snider ◽  
H.F. Wimer ◽  
S.S. Yamada ◽  
T. Yang ◽  
...  
Keyword(s):  
Root Formation ◽  
Tooth Eruption ◽  
Tooth Root

Ziyuglycoside I Upregulates RUNX2 through ERK1/2 in Promoting Osteoblast Differentiation and Bone Mineralization

2021 ◽  
pp. 1-18
Author(s):  
Kyung-Ran Park ◽  
Joon Yeop Lee ◽  
MyoungLae Cho ◽  
Hyung-Mun Yun
Keyword(s):  
Cell Migration ◽  
Osteoblast Differentiation ◽  
Bone Mineralization ◽  
Biological Effects ◽  
Bone Diseases ◽  
Nuclear Accumulation ◽  
Herbaceous Plant ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Alizarin Red

Sanguisorba officinalis L. (Rosaceae) is a perennial herbaceous plant and its roots have been used as an important traditional medicine for over 2000 years. Ziyuglycoside I (Ziyu), an active compound isolated from the roots of S. officinalis L., has shown biological effects such as anti-oxidant, antiviral, and antiwrinkle activities. This study aimed to elucidate the underlying mechanisms of action of Ziyu on cytotoxicity, migration, and differentiation of pre-osteoblasts. Herein, at concentrations ranging from 1 to 100 [Formula: see text]M, Ziyu was not cytotoxic against pre-osteoblasts. Alkaline phosphatase activity assay and staining, and migration assay showed that Ziyu increased cell migration and promoted early osteoblast differentiation, followed by the enhancement of mineralized nodule formation in a dose-dependent manner, as indicated by Alizarin Red S staining. In addition, Ziyu increased the protein levels of runt-related transcription factor 2 (RUNX2) during osteoblast differentiation, whereas it did not affect the phosphorylation of Smad1/5/8 and GSK3b and expression of [Formula: see text]-catenin. Ziyu also activated ERK1/2 and mitogen-activated protein kinase during osteoblast differentiation, and ERK1/2 inhibitor attenuated Ziyu-mediated RUNX2 expression and nuclear accumulation. Furthermore, Ziyu-mediated early and late osteoblast differentiation was significantly suppressed by the inhibition of ERK1/2, which was accompanied by attenuation in the mRNA levels of osteoblast-related genes including bone sialoprotein, osteopontin, and osteocalcin. Taken together, the findings of this study provide evidence that Ziyu promotes cell migration, osteoblast differentiation, and bone mineralization and suggest a potential role for Ziyu in the treatment of bone diseases.

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