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At least 433 records · Page 24
All sourcesNASA NTRSDOE OSTI
DOE OSTI2019

Broad band tunable energy electron beam pulser

An electromagnetic mechanical pulser implements a transverse wave metallic comb stripline TWMCS kicker having inwardly opposing teeth structured to retard a phase velocity of an RF traveling wave propagated therethrough to match the kinetic velocity of a continuous electron beam simultaneously propagated therethrough. The kicker imposes transverse oscillations onto the beam, which is subsequently chopped into pulses by an aperture. The RF phase velocity is substantially independent of RF frequency and amplitude, thereby enabling independent tuning of the electron pulse widths and repetition rate. The exterior surface of the kicker is conductive, thereby avoiding electron charging. In embodiments, various elements of the kicker and/or aperture can be mechanically varied to provide further tuning of the pulsed electron beam. A divergence suppression section can include a mirror TWMCS and/or magnetic quadrupoles. RF can be applied to a down-selecting TWMCS downstream of the aperture to reduce the pulse repetition rate.

Jing, Chunguang↗
DOE OSTI2020

Broad band tunable energy electron beam pulser

An electromagnetic mechanical pulser implements a transverse wave metallic comb stripline TWMCS kicker having inwardly opposing teeth that retards a phase velocity of an RF traveling wave to match the kinetic velocity of a continuous electron beam, causing the beam to oscillate before being chopped into pulses by an aperture. The RF phase velocity is substantially independent of RF frequency and amplitude, thereby enabling independent tuning of the electron pulse widths and repetition rate. The TWMCS further comprises an electron pulse picker (EPP) that applies a pulsed transverse electric field across the TWMCS to deflect electrons out of the beam, allowing only selected electrons and/or groups of electrons to pass through. The EPP pulses can be synchronized with the RF traveling wave and/or with a pumping trigger of a transverse electron microscope (TEM), for example to obtain dynamic TEM images in real time.

42 ENGINEERING↗
DOE OSTI2022

Results of ISO/TS 6336-22 Evaluating Full Contact Zone

ISO/TS 6336-22 (Calculation of load capacity of spur and helical gears - Part 22: Calculation of micropitting load capacity) is the ISO technical specification containing a proposal for calculations of the risk of micropitting in gear sets. Micropitting is a Hertzian fatigue phenomenon that appears as ultra-fine cracking and pitting on the flanks of gear teeth. Since progressive micropitting can lead to macropitting and flank damage, critical applications such as wind turbines, marine drives, and high-speed gear drives seek to accurately predict whether their designs are susceptible to this damage. ISO/TS 6336-22 assesses micropitting risk through a safety factor which is calculated as the minimum specific film thickness in the contact zone divided by a permissible specific film thickness. In the previous paper, the calculations were performed using the simplified method (Method B) that evaluates points on the path of contact. This was done for three gear sets that experienced micropitting in operation. The minimum specific film thickness for the two field cases was very high, which indicates that the gears were operating in the full elastohydrodynamic lubrication (EHL) regime. A more accurate calculation for these cases (Method A) calculates the specific film thickness across the entire contact zone. This paper applies this Method to the case study from the previous paper. The results are compared to micropitting observed in operation. Results are also compared to the results of the previous paper. Conclusions are made regarding the accuracy of both Methods compared to the field cases and relative to each other.

ENGINEERING,WIND ENERGY↗
DOE OSTI2022

Results of ISO/TS 6336-22 Evaluating Full Contact Zone: Preprint

ISO/TS 6336-22 (Calculation of load capacity of spur and helical gears — Part 22: Calculation of micropitting load capacity) is the ISO technical specification containing a proposal for calculations of the risk of micropitting in gear sets. Micropitting is a Hertzian fatigue phenomenon that appears as ultra-fine cracking and pitting on the flanks of gear teeth. Since progressive micropitting can lead to macropitting and flank damage, critical applications such as wind turbines, marine drives, and high-speed gear drives seek to accurately predict whether their designs are susceptible to this damage. ISO/TS 6336-22 assesses micropitting risk through a safety factor which is calculated as the minimum specific film thickness in the contact zone divided by a permissible specific film thickness. In the previous paper, the calculations were performed using the simplified method (Method B) that evaluates points on the path of contact. This was done for three gear sets that experienced micropitting in operation. The minimum specific film thickness for the two field cases was very high, which indicates that the gears were operating in the full elastohydrodynamic lubrication (EHL) regime. A more accurate calculation for these cases (Method A) calculates the specific film thickness across the entire contact zone. This paper applies this Method to the case study from the previous paper. The results are compared to micropitting observed in operation. Results are also compared to the results of the previous paper. Conclusions are made regarding the accuracy of both Methods compared to the field cases and relative to each other.

gearbox↗
DOE OSTI2022

Results of ISO/TS 6336-22 Evaluating Full Contact Zone

ISO/TS 6336-22 (Calculation of load capacity of spur and helical gears - Part 22: Calculation of micropitting load capacity) is the ISO technical specification containing a proposal for calculations of the risk of micropitting in gear sets. Micropitting is a Hertzian fatigue phenomenon that appears as ultra-fine cracking and pitting on the flanks of gear teeth. Since progressive micropitting can lead to macropitting and flank damage, critical applications such as wind turbines, marine drives, and high-speed gear drives seek to accurately predict whether their designs are susceptible to this damage. ISO/TS 6336-22 assesses micropitting risk through a safety factor which is calculated as the minimum specific film thickness in the contact zone divided by a permissible specific film thickness. In the previous paper, the calculations were performed using the simplified method (Method B) that evaluates points on the path of contact. This was done for three gear sets that experienced micropitting in operation. The minimum specific film thickness for the two field cases was very high, which indicates that the gears were operating in the full elastohydrodynamic lubrication (EHL) regime. A more accurate calculation for these cases (Method A) calculates the specific film thickness across the entire contact zone. This paper applies this Method to the case study from the previous paper. The results are compared to micropitting observed in operation. Results are also compared to the results of the previous paper. Conclusions are made regarding the accuracy of both Methods compared to the field cases and relative to each other.

gearbox↗
DOE OSTI2023

Electric motor cooling with oscillating heat pipes

A stator and a motor including a stator. The stator includes a stator hub, a plurality of stator teeth extending from the stator hub that define a stator slot having a stator slot base, at least one winding disposed in the stator slot, and one or more oscillating heat pipes disposed at least partially in the at least one winding. The at least one winding is held apart from the stator slot base so that a cooling channel is defined between an inner winding portion of the at least one winding and a portion of the one or more oscillating heat pipes is disposed in the channel so cooling fluid can be passed between the stator slot base and the inner winding portion to cool the inner winding portion via at least operation of the one or more oscillating heat pipes.

Alahyari, Abbas A.↗
DOE OSTI2018

Influence of Laser Nitriding on the Surface and Corrosion Properties of Ti-20Nb-13Zr Alloy in Artificial Saliva for Dental Applications

Ti alloys have been used for dentistry due to their lower density and improved compatibility. However, the resistance to corrosion and surface hardness of Ti alloys need to be improved to avoid the formation of debris, which affects the long-term biocompatibility. In the present work, the surface characteristics and corrosion protection in artificial saliva produced by laser nitriding of a new biomedical Ti-20Nb-13Zr at.% alloy have been investigated for dental applications. The laser nitrided and untreated alloy surfaces were examined using XRD, FE-SEM, x-ray photon spectroscopy, Vickers microhardness measurements, atomic force microscopy, scratch measurements, Raman spectroscopy, and surface energy measurements. The susceptibility of the laser nitrided TNZ alloy to corrosion in an artificial saliva medium was investigated by electrochemical corrosion tests, which were performed by utilizing open circuit potential monitoring, electrochemical frequency modulation, and electrochemical impedance spectroscopic methods. The findings revealed that a TiN layer formed on the alloy surface after nitriding. The surface hardness of the treated alloy was 2.4 times that of the as-received samples. Moreover, the results showed improved friction coefficient and hydrophilic surface characteristics. The corrosion analysis revealed that the compact and dense TiN layer produced during laser nitriding improved the corrosion resistance of the Ti-20Nb-13Zr sample in artificial saliva medium.

36 MATERIALS SCIENCE↗
DOE OSTI2026

Paleotribological models using preserved fossil tissue properties reveal functional significance of Eurasian mammoth dental evolution

Eurasian mammoths (Mammuthus) underwent substantial modifications in molar morphology as later-diverging species evolved progressively thinner enamel and increased enamel crest complexity. These features have been hypothesized to reduce whole-tooth wear and extend dental longevity as increasingly graze-dominated diets evolved within the lineage. This hypothesis has yet to be directly tested. Here, in this study, we developed an in-silico wear model using experimentally derived wear rates from fossil and extant proboscidean dental tissues. The models revealed that shifts in tissue topology do not affect whole-tooth wear rate, as inverse trends in lamellar frequency and enamel thickness preserve a consistent surface enamel area fraction; the determining factor of wear. Rather, topological shifts produce a wear-emergent secondary occlusal surface with greater numbers of triturating crests that create a regular, low-relief, file-like shearing pavement. These changes in occlusal architecture likely directly impacted the mastication capacity of Mammuthus dentitions, facilitating their dietary expansion to incorporate fibrous, lower-nutrient graze.

Dental wear↗
DOE OSTI2012

Characterization of p75{sup +} ectomesenchymal stem cells from rat embryonic facial process tissue

Highlights: Black-Right-Pointing-Pointer Ectomesenchymal stem cells (EMSCs) were found to migrate to rat facial processes at E11.5. Black-Right-Pointing-Pointer We successfully sorted p75NTR positive EMSCs (p75{sup +} EMSCs). Black-Right-Pointing-Pointer p75{sup +} EMSCs up to nine passages showed relative stable proliferative activity. Black-Right-Pointing-Pointer We examined the in vitro multilineage potential of p75{sup +} EMSCs. Black-Right-Pointing-Pointer p75{sup +}EMSCs provide an in vitro model for tooth morphogenesis. -- Abstract: Several populations of stem cells, including those from the dental pulp and periodontal ligament, have been isolated from different parts of the tooth and periodontium. The characteristics of such stem cells have been reported as well. However, as a common progenitor of these cells, ectomesenchymal stem cells (EMSCs), derived from the cranial neural crest have yet to be fully characterized. The aim of this study was to better understand the characteristics of EMSCs isolated from rat embryonic facial processes. Immunohistochemical staining showed that EMSCs had migrated to rat facial processes at E11.5, while the absence of epithelial invagination or tooth-like epithelium suggested that any epithelial-mesenchymal interactions were limited at this stage. The p75 neurotrophin receptor (p75NTR), a typical neural crest marker, was used to select p75NTR-positive EMSCs (p75{sup +} EMSCs), which were found to show a homogeneous fibroblast-like morphology and little change in the growth curve, proliferation capacity, and cell phenotype during cell passage. They also displayed the capacity to differentiate into diverse cell types under chemically defined conditions in vitro. p75{sup +} EMSCs proved to be homogeneous, stable in vitro and potentially capable of multiple lineages, suggesting their potential for application in dental or orofacial tissue engineering.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Proliferation and osteo/odontogenic differentiation of stem cells from apical papilla regulated by Zinc fingers and homeoboxes 2: An in vitro study

In the process of tooth root development, stem cells from the apical papilla (SCAPs) can differentiate into odontoblasts and form root dentin, however, molecules regulating SCAPs differentiation have not been elucidated. Zinc fingers and homeoboxes 2 (ZHX2) is a novel transcriptional inhibitor. It is reported to modulate the development of nerve cells, liver cells, B cells, red blood cells, and so on. However, the role of ZHX2 in tooth root development remains unclear. In this study, we explored the potential role of ZHX2 in the process of SCAPs differentiation. The results showed that overexpression of ZHX2 upregulated the expression of osteo/odontogenic related genes and ALP activity, inhibited the proliferation of SCAPs. Consistently, ZHX2 knockdown reduced SCAPs mineralization and promoted SCAPs proliferation. These results indicated that ZHX2 plays a critical role in the proliferation and osteo/odontogenic differentiation of SCAPs. - Highlights: • Zinc fingers and homeoboxes 2 (ZHX2) is a novel transcriptional inhibitor. • we found another new biological function of ZHX2 for the first time. • ZHX2 inhibit SCAPs proliferation. • ZHX2 promote the osteo/odontogenic differentiation of SCAPs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Harmine promotes molar root development via SMAD1/5/8 phosphorylation

Tooth and bone are major tissues involved in physiological calcification in the body, and they use similar molecular pathways for development, homeostasis, and regeneration. Harmine (HMN) is a natural small compound that stimulates osteoblast differentiation in vitro and in vivo. Here we examined the biological effect of HMN on the postnatal development of molar tooth roots and periodontal tissues. HMN supported the formation of tooth roots and periodontal tissues in developing tooth germs. In tooth germ organ culture, HMN promoted the elongation of Hertwig's epithelial root sheath (HERS) and stimulated cell proliferation in HERS and dental follicle-derived tissues, including dental papillae and dental follicles. HMN stimulated cell proliferation and cell movement of HERS-derived cells without mesenchymal cells in vitro and directly induced the phosphorylation of SMAD1/5/8 protein in HERS-derived cells. Our results indicated that HMN was the first natural small compound to stimulate postnatal development of tooth germs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2013

Histone deacetylase inhibitors epigenetically promote reparative events in primary dental pulp cells

Application of histone deacetylase inhibitors (HDACi) to cells epigenetically alters their chromatin structure and induces transcriptional and cellular reparative events. This study investigated the application of two HDACi, valproic acid (VPA) and trichostatin A (TSA) on the induction of repair-associated responses in primary dental pulp cell (DPC) cultures. Flow cytometry demonstrated that TSA (100 nM, 400 nM) significantly increased cell viability. Neither HDACi was cytotoxic, although cell growth analysis revealed significant anti-proliferative effects at higher concentrations for VPA (>0.5 mM) and TSA (>50 nM). While high-content-analysis demonstrated that HDACi did not significantly induce caspase-3 or p21 activity, p53-expression was increased by VPA (3 mM, 5 mM) at 48 h. HDACi-exposure induced mineralization per cell dose-dependently to a plateau level (VPA-0.125 mM and TSA-25 nM) with accompanying increases in mineralization/dentinogenic-associated gene expression at 5 days (DMP-1, BMP-2/-4, Nestin) and 10 days (DSPP, BMP-2/-4). Both HDACis, at a range of concentrations, significantly stimulated osteopontin and BMP-2 protein expression at 10 and 14 days further supporting the ability of HDACi to promote differentiation. HDACi exert different effects on primary compared with transformed DPCs and promote mineralization and differentiation events without cytotoxic effects. These novel data now highlight the potential in restorative dentistry for applying low concentrations of HDACi in vital pulp treatment. -- Highlights: • Valproic acid and trichostatin A promoted mineralization in primary pulp cells. • Cell viability, apoptosis, caspase-3, p21 unaltered; p53 increased by valproic acid. • Trichostatin A increased cell viability at 24 h at selected concentrations. • Altered cell toxicity and differentiation between primary and transformed cells. • HDACi-induced the differentiation marker proteins osteopontin and BMP-2.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2014

Multilineage potential and proteomic profiling of human dental stem cells derived from a single donor

Dental tissues provide an alternative autologous source of mesenchymal stem cells (MSCs) for regenerative medicine. In this study, we isolated human dental MSCs of follicle, pulp and papilla tissue from a single donor tooth after impacted third molar extraction by excluding the individual differences. We then compared the morphology, proliferation rate, expression of MSC-specific and pluripotency markers, and in vitro differentiation ability into osteoblasts, adipocytes, chondrocytes and functional hepatocyte-like cells (HLCs). Finally, we analyzed the protein expression profiles of undifferentiated dental MSCs using 2DE coupled with MALDI-TOF-MS. Three types of dental MSCs largely shared similar morphology, proliferation potential, expression of surface markers and pluripotent transcription factors, and differentiation ability into osteoblasts, adipocytes, and chondrocytes. Upon hepatogenic induction, all MSCs were transdifferentiated into functional HLCs, and acquired hepatocyte functions by showing their ability for glycogen storage and urea production. Based on the proteome profiling results, we identified nineteen proteins either found commonly or differentially expressed among the three types of dental MSCs. In conclusion, three kinds of dental MSCs from a single donor tooth possessed largely similar cellular properties and multilineage potential. Further, these dental MSCs had similar proteomic profiles, suggesting their interchangeable applications for basic research and call therapy. - Highlights: • Isolated and characterized three types of human dental MSCs from a single donor. • MSCs of dental follicle, pulp and papilla had largely similar biological properties. • All MSCs were capable of transdifferentiating into functional hepatocyte-like cells. • 2DE proteomics with MALDI-TOF/MS identified 19 proteins in three types of MSCs. • Similar proteomic profiles suggest interchangeable applications of dental MSCs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Nuclear Factor I-C promotes proliferation and differentiation of apical papilla-derived human stem cells in vitro

The transcription factor Nuclear Factor I-C (NFIC) has been implicated in the regulation of tooth root development, where it may be anticipated to impact on the behavior of stem cells from the apical papilla (SCAPs) and root odontoblast activity. We hypothesized that NFIC may provide an important target for promoting dentin/root regeneration. In the present study, the effects of NFIC on the proliferation and differentiation of SCAPs were investigated. Over-expression of NFIC increased cell proliferation, mineralization nodule formation and alkaline phosphatase (ALP) activity in SCAPs. Furthermore, NFIC up-regulated the mRNA levels of odontogenic-related markers, ALP, osteocalcin and collagen type I as well as dentin sialoprotein protein levels. In contrast, knockdown of NFIC by si-RNA inhibited the mineralization capacity of SCAPs and down-regulated the expression of odontogenic-related markers. In conclusion, the results indicated that upregulation of NFIC activity in SCAPs may promote osteo/odontoblastic differentiation of SCAPs. - Highlights: • NFIC promotes the proliferation of SCAPs in vitro. • NFIC promotes osteo/odontogenic differentiation of SCAPs in vitro. • Knockdown of NFIC inhibits odontogenic differentiation in SCAPs.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

Wnt5a attenuates Wnt3a-induced alkaline phosphatase expression in dental follicle cells

Wnt signaling regulates multiple cellular events such as cell proliferation, differentiation, and apoptosis through β-catenin-dependent canonical and β-catenin-independent noncanonical pathways. Canonical Wnt/β-catenin signaling can promote the differentiation of dental follicle cells, putative progenitor cells for cementoblasts, osteoblasts, and periodontal ligament cells, toward a cementoblast/osteoblast phenotype during root formation, but little is known about the biological significance of noncanonical Wnt signaling in this process. We identified the expression of Wnt5a, a representative noncanonical Wnt ligand, in tooth root lining cells (i.e. precementoblasts/cementoblasts) and dental follicle cells during mouse tooth root development, as assessed by immunohistochemistry. Silencing expression of the Wnt5a gene in a dental follicle cell line resulted in enhancement of the Wnt3a (a representative canonical Wnt ligand)-mediated increase in alkaline phosphatase (ALP) expression. Conversely, treatment with recombinant Wnt5a inhibited the increase in ALP expression, suggesting that Wnt5a signaling functions as a negative regulator of canonical Wnt-mediated ALP expression of dental follicle cells. Wnt5a did not affect the nuclear translocation of β-catenin as well as β-catenin-mediated transcriptional activation of T-cell factor (Tcf) triggered by Wnt3a, suggesting that Wnt5a inhibits the downstream part of the β-catenin-Tcf pathway. These findings suggest the existence of a feedback mechanism between canonical and noncanonical Wnt signaling during the differentiation of dental follicle cells. - Highlights: • Dental follicle cells express Wnt5a during tooth root development. • Silencing of Wnt5a enhances Wnt3a-mediated ALP expression of dental follicle cells. • Conversely, treatment with rWnt5a inhibited the increase in ALP expression. • Wnt5a functions as a negative regulator of Wnt3a-mediated ALP expression.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2015

In vitro cementoblast-like differentiation of postmigratory neural crest-derived p75{sup +} stem cells with dental follicle cell conditioned medium

Cranial neural crest-derived cells (CNCCs) play important role in epithelial–mesenchymal interactions during tooth morphogenesis. However, the heterogeneity of CNCCs and their tendency to spontaneously differentiate along smooth muscle or osteoblast lineages in vitro limit further understanding of their biological properties. We studied the differentiation properties of isolated rat embryonic postmigratory CNCCs, expressing p75 neurotrophin receptor (p75NTR). These p75NTR positive (p75{sup +}) CNCCs, isolated using fluorescence activated cell sorter, exhibited fibroblast-like morphology and characteristics of mesenchymal stem cells. Incubation of p75{sup +} CNCCs in dental follicle cell conditioned medium (DFCCM) combined with dentin non-collagenous proteins (dNCPs), altered their morphological features to cementoblast-like appearance. These cells also showed low proliferative activity, high ALP activity and significantly increased calcified nodule formation. Markers related to mineralization or specific to cementoblast lineage were highly expressed in dNCPs/DFCCM-treated p75{sup +} cells, suggesting their differentiation along cementoblast-like lineage. p75{sup +} stem cells selected from postmigratory CNCCs represent a pure stem cell population and could be used as a stem cell model for in vitro studies due to their intrinsic ability to differentiate to neuronal cells and transform from neuroectoderm to ectomesenchyme. They can provide a potential stem cell resource for tooth engineering studies and help to further investigate mechanisms of epithelial–mesenchymal interactions in tooth morphogenesis. - Highlights: • Cranial neural crest-derived cells (CNCCs) take part in tooth morphogenesis. • positive (p75{sup +}) CNCCs are fibroblast-like and resemble mesenchymal stem cells. • p75{sup +} CNCCs in dental follicle cell medium (DFCCM/dNCP) appear like cementoblasts. • DFCCM/dNCP-treated p75{sup +} cells express cementoblast specific mineralization markers. • p75{sup +} cells are pure stem cells and able to differentiate to neuronal cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Bcl-2 expression is essential for development and normal physiological properties of tooth hard tissue and saliva production

Background: Apoptosis plays a fundamental role in appropriate tissue development and function. Although expression of Bcl-2 has been reported during tooth and submandibular gland (SMG) development, the physiological role Bcl-2 plays during these processes has not been addressed. This study was performed to evaluate the impact of Bcl-2 expression on the formation and properties of tooth hard tissue, and saliva production. Methods: Twenty-four mice (12 males and 12 females) were divided into three groups of eight (n=8): group A (Bcl-2 +/+), group B (Bcl-2 +/-), and group C (Bcl-2 -/-) and subjected to micro-CT analyses. The mineral content of first molars was analyzed by X-Ray diffraction (XRD) and scanning electron microscopy (SEM) color dot map. The surface microhardness was determined by Vickers test on labial surfaces of incisors. Saliva was collected from different groups of mice after subcutaneous injection of pilocarpine. Results: Samples from Bcl-2 -/- mice showed significantly smaller micro-CT values, lower and poor crystallinity of hydroxyapatite (HA), and lowest surface micro hardness. SMG from Bcl-2 -/- mice showed remarkable reduction in size, consistent with reduced saliva accumulation. Conclusions: The absence of Bcl-2 expression in SMG did not affect the expression of other Bcl-2 family members. Thus, Bcl-2 expression influence on the formation and properties of tooth hard tissue, and saliva accumulation. Significance: Bcl-2 expression has a significant impact on the mineralogical content of enamel crystals of tooth structure. Lack of Bcl-2 expression led to impaired production of enamel ACP crystals. - Highlights: • Lack of Bcl-2 expression led to impaired production of enamel ACP crystals. • Germline deletion of Bcl-2 reduced the surface microhardness of enamel. • Bcl-2 expression is vitally important for SMG function and saliva production. • Lack of Bcl-2 expression was not compensated by expression of other Bcl-2 family members.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Abrogation of Fam20c altered cell behaviors and BMP signaling of immortalized dental mesenchymal cells

Highlights: • Fam20c deficiency decreases the proliferation, mobility and mineralization of mouse immortalized dental mesenchymal cells. • Fam20c deficiency decreases the tooth mineralization, as well as the gene expression on dental mesenchymal differentiation. • Canonical and non-canonical BMP signaling pathways are declined in the mouse Fam20c-deficient dental mesenchyaml cell line. FAM20C mutations compromise the mineralization of skeleton and tooth in both human and mouse. Putatively, the mineralization disorder is attributed to the elevated fibroblast growth factor 23 (FGF23), which reduced the serum phosphorus by suppressing the reabsorption of phosphorus in kidney. Besides the regulation on systemic phosphorus homeostasis, FAM20C was also implicated to regulate cell behaviors and gene expression through a cell-autonomous manner. To identify the primary effects of Fam20c on dental mesenchymal cells, mouse Fam20c-deficient dental mesenchymal cells were generated by removing the floxed alleles from the immortalized mouse Fam20c{sup f/f} dental mesenchymal cells with Cre-expressing lentivirus. The removal of Fam20c exerted no impact on cell morphology, but suppressed the proliferation and mobility of the dental mesenchymal cells. Fam20c deficiency also significantly reduced the expression of Osterix, Runx2, type I Collagen a 1 (Col1a1), Alkaline phosphatase (Alpl) and the members of the small integrin-binding ligand, N-linked glycoprotein (SIBLING) family, but increased Fgf23 expression. Consistently, the in vitro mineralization of Fam20c-deficient dental mesenchymal cells was severely disabled. However, supplements of the non-collagenous proteins from wild type rat dentin failed to rescue the compromised mineralization, suggesting that the roles of FAM20C in tooth mineralization are more than phosphorylating local matrices and regulating systemic phosphorus metabolism. Moreover, the down-regulated BMP signaling pathways in the Fam20c deficient dental mesenchymal cells revealed that the kinase activity of FAM20C might be required to maintain BMP signaling. In summary, our study discloses that Fam20c indeed regulates cell behaviors and cell signaling pathway in a cell-autonomous manner.

60 APPLIED LIFE SCIENCES↗