High Levels of BPA and BPF Exposure during Pregnancy Are Associated with Lower Birth Weight in Shenyang in Northeast China.

Animal studies indicate that bisphenol A (BPA) has obesogenic effects. Recent experiments reported similar endocrine-disrupting effects of bisphenol F (BPF) and bisphenol S (BPS), which are substitutes of BPA. The aim of this study was to investigate the exposure levels of these bisphenols in pregnant women and their effects on the physical development of infants aged 0-12 months. This study recruited pregnant women who gave birth at a hospital between February 2019 and September 2020. Urine samples from these pregnant women in the third trimester of pregnancy were detected by using ultrahigh-performance liquid chromatography-triple quadruple mass spectrometry. Follow-ups at 6 and 12 months of age were conducted by telephone by pediatricians using a structured questionnaire. Multiple linear regressions were used to determine the associations between bisphenol concentrations and infant weight. A total of 113 mother-child pairs had complete questionnaires and urine samples as well as data on newborns aged 6 months and 12 months. The detection rates of urinary BPA, BPF, and BPS in pregnant women were 100, 62.83, and 46.02%, respectively. Their median levels are 5.84, 0.54, and 0.07 µg/L, respectively. Increased urinary BPA and BPF concentrations during pregnancy were significantly associated with lower birth weight (standardized regression coefficients [ß] = -0.081 kg, 95% confidence interval [CI]: -0.134 to -0.027; ß = -0.049 kg, 95% CI: -0.097 to -0.001). In addition, urinary BPA and BPF concentrations during pregnancy were positively associated with weight growth rate from 0 to 6 months (ß = 0.035 kg/mouth, 95% CI: 0.00-0.064; ß = 0.028 kg/mouth, 95% CI: 0.006-0.050), especially in female infants (ß = 0.054 kg/mouth, 95% CI: 0.015-0.093; ß = 0.035 kg/mouth, 95% CI: 0.005-0.065). Therefore, maternal BPA and BPF levels during pregnancy were negatively correlated with birth weight and positively correlated with the growth rate of infant weight at 0-6 months of age, especially in female infants.

Development and regeneration of periodontal supporting tissues.

Periodontal tissues, including gingiva, cementum, periodontal ligament, and alveolar bone, play important roles in oral health. Under physiological conditions, periodontal tissues surround and support the teeth, maintaining the stability of the teeth and distributing the chewing forces. However, under pathological conditions, with the actions of various pathogenic factors, the periodontal tissues gradually undergo some irreversible changes, that is, gingival recession, periodontal ligament rupture, periodontal pocket formation, alveolar bone resorption, eventually leading to the loosening and even loss of the teeth. Currently, the regenerations of the periodontal tissues are still challenging. Therefore, it is necessary to study the development of the periodontal tissues, the principles and processes of which can be used to develop new strategies for the regeneration of periodontal tissues. This review summarizes the development of periodontal tissues and current strategies for periodontal healing and regeneration.

Acvr1 deletion in osteoblasts impaired mandibular bone mass through compromised osteoblast differentiation and enhanced sRANKL-induced osteoclastogenesis.

Bone morphogenetic protein (BMP) signaling is well known in bone homeostasis. However, the physiological effects of BMP signaling on mandibles are largely unknown, as the mandible has distinct functions and characteristics from other bones. In this study, we investigated the roles of BMP signaling in bone homeostasis of the mandibles by deleting BMP type I receptor Acvr1 in osteoblast lineage cells with Osterix-Cre. We found mandibular bone loss in conditional knockout mice at the ages of postnatal day 21 and 42 in an age-dependent manner. The decreased bone mass was related to compromised osteoblast differentiation together with enhanced osteoclastogenesis, which was secondary to the changes in osteoblasts in vivo. In vitro study revealed that deletion of Acvr1 in the mandibular bone marrow stromal cells (BMSCs) significantly compromised osteoblast differentiation. When wild type bone marrow macrophages were cocultured with BMSCs lacking Acvr1 both directly and indirectly, both proliferation and differentiation of osteoclasts were induced as evidenced by an increase of multinucleated cells, compared with cocultured with control BMSCs. Furthermore, we demonstrated that the increased osteoclastogenesis in vitro was at least partially due to the secretion of soluble receptor activator of nuclear factor-κB ligand (sRANKL), which is probably the reason for the mandibular bone loss in vivo. Overall, our results proposed that ACVR1 played essential roles in maintaining mandibular bone homeostasis through osteoblast differentiation and osteoblast-osteoclast communication via sRANKL.

Intelligent pH indicator films containing anthocyanins extracted from blueberry peel for monitoring tilapia fillet freshness.

BACKGROUND: Fish spoilage leads to an increase in the pH value of the fish. A colorimetric pH indicator can be used to monitor fish spoilage and has been exploited in intelligent packaging because of its simplicity, practicality and low cost. The aim of this study was to develop two pH-indicator films comprising starch (S), tara gum (TG), polyvinyl alcohol (PVA) and anthocyanins extracted from blueberry peel and the films were then used to monitor the freshness of tilapia fillets during storage at 25 and 4 °C. RESULTS: The ultraviolet-visible (UV-visible) spectra and color of anthocyanins changed within pH 2-10. Fourier-transform infrared spectroscopy, UV-visible spectrophotometry and scanning electron microscopy certified that blueberry peel extract (BPE) had been introduced into the S/PVA and TG/PVA matrices. Visual color changes in the films occurred at pH 2-8. A freshness application test was conducted in tilapia fillets stored at 4 and 25 °C, and visual color changes in the films were observed. The TG/PVA/BPE film had a greater color difference (ΔE) from pink and transparent to dark yellow at 25 °C and to dark purple at 4 °C than ΔE of S/PVA/BPE film, which sufficiently correlated with the change of total volatile base nitrogen (TVB-N) and total aerobic counts (TACs) of fillets. CONCLUSION: It can be concluded that the color changes of TG/PVA/BPE films were corresponded with TVB-N and TAC values of tilapia fillets, which presented great potential as a visual package label to monitor fish freshness at ambient and chilled temperatures. © 2020 Society of Chemical Industry.

An ammonia-sensitive fluorescence sensor based on polyvinyl alcohol-graphene quantum dots/halloysite nanotubes hybrid film for monitoring fish freshness.

A fluorescent hybrid film composed of nitrogen-doped graphene quantum dots (N-GQDs) loaded on halloysite nanotubes (HNTs) (N-GQDs/HNTs nanocomposite) as a sensitive element and polyvinyl alcohol (PVA) as a film-forming matrix was designed for freshness detection. The PVA-N-GQDs/HNTs hybrid film exhibited significantly enhanced fluorescence attributed to the loading of N-GQDs onto the surface of HNTs through electrostatic interactions and hydrogen bonding, effectively reducing their aggregation. The fluorescence of the hybrid film could be quenched by ammonia via photoinduced electron transfer (PET), with good linearity in the range of 20 ppm to 500 ppm ammonia and a limit of detection (LOD) of 0.63 ppm. In addition, the hybrid film was applied to monitor the freshness of seawater fish and freshwater fish stored at refrigeration and room temperature to evaluate the practicality of this approach. The developed hybrid film showed promise for nondestructive and on-site monitoring of fish spoilage.

Ethyl cellulose/gelatin-carboxymethyl chitosan bilayer films doped with Euryale ferox seed shell polyphenol for cooked meat preservation.

This study evaluated the effects of an edible bilayer containing polyphenols from the Euryale ferox seed shell on ready-to-eat cooked beef products, including the physical, mechanical, antioxidant, and antibacterial capabilities. Here, the bilayer films were prepared by layer-by-layer solution pouring using hydrophobic ethyl cellulose (EC) as the outer layer, and hydrophilic gelatin/carboxymethyl chitosan (GC) as the inner layer. By adjusting the proportion of gelatin to carboxymethyl chitosan, the optical, mechanical, and barrier characteristics of bilayer films were markedly enhanced. Extracted polyphenol (EP) from shell of the Euryale ferox seed performed potent antibacterial property against Listeria monocytogenes (L. monocytogenes). The addition of EP to the inner layer of the optimized bilayer film further improved the mechanical and barrier properties of films, and as expected, the film exhibited antioxidant and antibacterial abilities. Additionally, cooked beef and cooked chicken preservation tests indicated that the active bilayer film showed good inhibition of L. monocytogenes and delayed lipid oxidation in ready-to-eat meat products, and significantly delayed the pH, moisture loss, color and texture changes. This study developed multifunctional bilayer active edible films, which has a great potential in the preservation ready-to-eat cooked meat products.

Preparation of waterborne anti-counterfeiting ink based on dual luminescent nanohybrids of bacterial cellulose nanocrystals and lanthanide­nitrogen co-modified GQDs.

To address the growing challenge of counterfeit prevention, this study developed a novel anti-counterfeiting ink system based on bacterial cellulose nanocrystals (BCNC) and lanthanide (Er, Yb)­nitrogen (N) co-dropped graphene quantum dots (GQDs), which exhibited both photoluminescence (PL) and upconversion photoluminescence (UCPL) fluorescent properties as well as excellent rheological characteristics. The Er/Yb/N-GQDs with positive charges were synthesized by a one-step hydrothermal method and subsequently assembled with negatively charged BCNC through electrostatic self-assembly to fabricate a novel nanohybrid, Er/Yb/N-GQDs-BCNC. Raman spectroscopy results indicated an enhancement in the graphitization of GQDs due to lanthanide modification. The TEM results demonstrated a homogeneous distribution of Er/Yb/N-GQDs on BCNC, while XRD, FTIR, and XPS analyses confirmed their physical binding, thus validating the successful synthesis of novel nanohybrids. Then, Er/Yb/N-GQDs-BCNC was introduced into PVA waterborne ink and exhibited dual anti-counterfeiting properties by emitting blue fluorescence at Em 440 nm under Ex 370 nm and green fluorescence at Em 550 nm under Ex 980 nm. Furthermore, the incorporation of BCNC significantly enhanced the thixotropic behavior and yield stress of the PVA waterborne ink. This enhancement made the dual anti-counterfeiting fluorescent ink more suitable for diversified applications on different devices and various substrates, thus providing a novel approach for convenient and rapid information encryption and high security anti-counterfeiting.

BMP signaling in the development and regeneration of tooth roots: from mechanisms to applications.

Short root anomaly (SRA), along with caries, periodontitis, and trauma, can cause tooth loss, affecting the physical and mental health of patients. Dental implants have become widely utilized for tooth restoration; however, they exhibit certain limitations compared to natural tooth roots. Tissue engineering-mediated root regeneration offers a strategy to sustain a tooth with a physiologically more natural function by regenerating the bioengineered tooth root (bio-root) based on the bionic principle. While the process of tooth root development has been reported in previous studies, the specific molecular mechanisms remain unclear. The Bone Morphogenetic Proteins (BMPs) family is an essential factor regulating cellular activities and is involved in almost all tissue development. Recent studies have focused on exploring the mechanism of BMP signaling in tooth root development by using transgenic animal models and developing better tissue engineering strategies for bio-root regeneration. This article reviews the unique roles of BMP signaling in tooth root development and regeneration.

Polypropylene fiber grafted calcium alginate with mesoporous silica for adsorption of Bisphenol A and Pb2.

Polypropylene grafted calcium alginate with mesoporous silica (PP-g-CaAlg@SiO2) for adsorbing Bisphenol A (BPA) and Pb2+ was prepared by calcium chloride (CaCl2) crosslinking and hydrochloric acid solution treatment. The PP-g-CaAlg@SiO2 was characterized by SEM, TEM, BET, XRD, FTIR and TG. PP-g-CaAlg@SiO2 exhibited excellent adsorption capacity for BPA and Pb2+, because the formation of reticulated nanorod structure increased its specific surface area. Subsequently, the adsorption behaviours of BPA and Pb2+, including adsorption isotherms and adsorption kinetics, were investigated. Afterward, isothermal titration calorimetry (ITC) and molecular dynamics (MD) simulation were performed to explore the adsorption mechanism. The results indicated that hydrogen bonding played the leading role in the adsorption of BPA, while the bonding of Pb2+ to carboxyl group binding sites was the focus of Pb2+ adsorption. In addition, the adsorption capacity of PP-g-CaAlg@SiO2 was stable over 10 cycles.

Preparation and characterization of intelligent packaging film for visual inspection of tilapia fillets freshness using cyanidin and bacterial cellulose.

An intelligent pH-sensitive film was developed by incorporating cyanidin-3-glucoside (C3G) into bacterial cellulose (BC), and its application as a freshness indicator for tilapia fillets was investigated. The physical properties of the film were characterized using Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), and X-ray diffraction (XRD). The results demonstrated the mechanical properties of the film were significantly changed due to higher crystallinity induced by C3G. XRD and FTIR analysis showed the increased crystallinity and transmittance intensity of the BC-C3G film. Moreover, this film exhibited distinctive color changes from red to green when exposed to buffers with a pH of 3 to 10. In accordance with changes in total volatile basic nitrogen (TVB-N) and total viable count (TVC) of tilapia fillets, the indicator demonstrated visualized color changes as rose-red (fresh), purple (still suitable), and lavender (spoiled) during storage at both 25 °C and 4 °C. The results suggest that this film has great potential to be used as an intelligent indicator to monitor the freshness of fish.

An intelligent colorimetric film based on complex anthocyanins and bacterial cellulose nanofibers for tilapia freshness detection in an actual cold chain.

An intelligent colorimetric film was developed for the quality detection of tilapia fillets using bacterial cellulose (BC) as a substrate in combination with pelargonidin (Pg), cyanidin (Cy), and delphinium (Dp). The color of the BC-Pg-Cy-Dp film and Pg-Cy-Dp solution changed from rosy to blue-violet at pH 3-10. The mechanical and antioxidant properties of the film were improved after the addition of Pg-Cy-Dp. Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) showed that a new hydrogen bond might be formed between the cellulose chain and the anthocyanin molecule, which increased the density of the film. The BC-Pg-Cy-Dp film displayed a large color difference from rosy to blue-violet when applied to tilapia fillet storage. The changes of K values indicated a good linear relationship with the change in ∆E at 4 °C and 25 °C. In the actual cold chain, the color of the film changed from rosy to purple, which could be identified by the naked eye and indicated that the fish were in the first fresh stage. Thus, the BC-Pg-Cy-Dp film can be used as an intelligent packaging film during storage to monitor the freshness of fish by the naked eye.

Roles of Immune Cells and Mechanisms of Immune Responses in Periodontitis.

Periodontitis is one of the severe oral diseases that threatens both the oral and general health of humans. It is an inflammatory disease caused by the complex interaction between the plaque microorganisms and the host immune system. The innate immune response is activated when pathogens invade the periodontium. An excessive innate immune response leads to inflammation and the destruction of periodontal tissues, which then activates the adaptive immune response. Although systemic initial therapy and guided tissue regeneration (GTR) can control periodontal inflammation to a certain extent and promote periodontal tissue regeneration, their effects are still limited. Periodontal treatment will be significantly improved if it is possible to screen the potential therapeutic targets and regulate the key molecules involved in periodontal disease; however, relevant research on the prevention and treatment of periodontitis remains limited. Thus, with the aim of assisting the immunoregulation of periodontitis, this article summarises the cells and mechanisms involved in the innate immune response and adaptive immune response caused by pathogens in the periodontium.

Osteoclast differentiation and formation induced by titanium implantation through complement C3a.

Titanium implantation is widely used for dental replacement with advantages of excellent mechanical strength, corrosion resistance, chemical stability and biocompatibility. Some patients, however, are subject to the failure of implantation due to bone resorption, which closely related to the inflammatory responses without clear mechanisms. In this study, first we found that there were inflammatory responses and increases of osteoclasts in the surrounding tissues near by the titanium implant. Further, data revealed that the C3 was increased in the serum and surrounding tissues near by the titanium implant, and activated by classical and alternative pathways. Next, we recognized that the C3a/C3aR, no C3b played an important role in stimulating secretions of pro-inflammatory cytokines of TNF-α and MMP9 via transcription factors NF-kB and NFATc1. This cascade of responses to titanium implant leaded the differentiation and proliferation of osteoclasts in vivo and in vitro, bone resorption of surrounding tissues of Ti implant. These suggest that the cleaved C3a fragment plays predominant roles in the activation of osteoclast. Therefore, the blocking C3a activation should provide potential to prevent bone resorption and prolong the survival of biomaterial implants.

Model-based process development and evaluation of twin-column continuous capture processes with Protein A affinity resin.

Multi-column continuous chromatography has advantages of high resin capacity utilization and productivity, low buffer consumption and small footprint. Experimental optimization is often time-consuming and inefficient due to the complexity of continuous processes. In this study, a model-based approach was investigated to improve process development of twin-column continuous capture with Protein A affinity resin MabSelect PrismA. Breakthrough curves under various conditions, productivity and capacity utilization (CU) of the continuous processes under varying operating conditions were predicted. Effects of three key operating parameters (feed concentration (c0), interconnected feed residence time (RT) and breakthrough percentage control of the first column during interconnected feeding (s)) on the productivity and CU were evaluated. A recommended working window can be determined directly from contour maps to balance the trade-off between productivity and CU. The model-optimized operating conditions at varying feed concentrations were verified by experiments, which indicated that the model-based approach was feasible and reliable. The results showed that the suitable RT was 1~2 min and suitable s was 0.6~0.75 for the continuous IgG capture with MabSelect PrismA. The maximum productivity varied from 14 to 47 g/L/h with the feed IgG concentrations at the range of 1 to 10 mg/mL. The results indicated that model-based approach could assist process development efficiently and promote target-orientated process design for continuous processes.

Haploinsufficiency of Dspp Gene Causes Dentin Dysplasia Type II in Mice.

Dentin dysplasia (DD) and dentinogenesis imperfecta (DGI) patients have abnormal structure, morphology, and function of dentin. DD-II, DGI-II, and DGI-III are caused by heterozygous mutations in the dentin sialophosphoprotein (DSPP) gene in humans. Evidences have shown that loss of function of DSPP in Dspp knockout mice leads to phenotypes similar to DGI-III, and that the abnormal dentinogenesis is associated with decreased levels of DSPP, indicating that DSPP haploinsufficiency may play a role in dentinogenesis. Thus, to testify the haploinsufficiency of Dspp, we used a Dspp heterozygous mouse model to observe the phenotypes in the teeth and the surrounding tissues. We found that Dspp heterozygous mice displayed dentin phenotypes similar to DD-II at the ages of 12 and 18 months, which was characterized by excessive attrition of the enamel at the occlusal surfaces, thicker floor dentin of the pulp chamber, decreased pulp volume, and compromised mineralization of the dentin. In addition, the periodontium was also affected, exhibiting apical proliferation of the junctional epithelium, decreased height and width of the alveolar bone, and infiltration of the inflammatory cells, leading to the destruction of the periodontium. Both the dental and periodontal phenotypes were age-dependent, which were more severe at 18 months old than those at 12 months old. Our report is the first to claim the haploinsufficiency of Dspp gene and a DD-II mouse model, which can be further used to study the molecular mechanisms of DD-II.

Distinctive role of ACVR1 in dentin formation: requirement for dentin thickness in molars and prevention of osteodentin formation in incisors of mice.

Dentin is a major component of teeth that protects dental pulp and maintains tooth health. Bone morphogenetic protein (BMP) signaling is required for the formation of dentin. Mice lacking a BMP type I receptor, activin A receptor type 1 (ACVR1), in the neural crest display a deformed mandible. Acvr1 is known to be expressed in the dental mesenchyme. However, little is known about how BMP signaling mediated by ACVR1 regulates dentinogenesis. To explore the role of ACVR1 in dentin formation in molars and incisors in mice, Acvr1 was conditionally disrupted in Osterix-expressing cells (designated as cKO). We found that loss of Acvr1 in the dental mesenchyme led to dentin dysplasia in molars and osteodentin formation in incisors. Specifically, the cKO mice exhibited remarkable tooth phenotypes characterized by thinner dentin and thicker predentin, as well as compromised differentiation of odontoblasts in molars. We also found osteodentin formation in the coronal part of the cKO mandibular incisors, which was associated with a reduction in the expression of odontogenic gene Dsp and an increase in the expression of osteogenic gene Bsp, leading to an alteration of cell fate from odontoblasts to osteoblasts. In addition, the expressions of WNT antagonists, Dkk1 and Sost, were downregulated and B-catenin was up-regulated in the cKO incisors, while the expression levels were not changed in the cKO molars, compared with the corresponding controls. Our results indicate the distinct and critical roles of ACVR1 between incisors and molars, which is associated with alterations in the WNT signaling related molecules. This study demonstrates for the first time the physiological roles of ACVR1 during dentinogenesis.

An injectable and thermosensitive hydrogel: Promoting periodontal regeneration by controlled-release of aspirin and erythropoietin.

Periodontitis is an inflammatory disease induced by complex interactions between host immune system and plaque microorganism. Alveolar bone resorption caused by periodontitis is considered to be one of the main reasons for tooth loss in adults. To terminate the alveolar bone resorption, simultaneous anti-inflammation and periodontium regeneration is required, which has not appeared in the existing methods. In this study, chitosan (CS), ß-sodium glycerophosphate (ß-GP), and gelatin were used to prepare an injectable and thermosensitive hydrogel, which could continuously release aspirin and erythropoietin (EPO) to exert pharmacological effects of anti-inflammation and tissue regeneration, respectively. The releasing profile showed that aspirin and EPO could be continuously released from the hydrogels, which exhibited no toxicity both in vitro and in vivo, for at least 21 days. Immunohistochemistry staining and micro-CT analyses indicated that administration of CS/ß-GP/gelatin hydrogels loaded with aspirin/EPO could terminate the inflammation and recover the height of the alveolar bone, which is further confirmed by histological observations. Our results suggested that CS/ß-GP/gelatin hydrogels are easily prepared as drug-loading vectors with excellent biocompatibility, and the CS/ß-GP/gelatin hydrogels loaded with aspirin/EPO are quite effective in anti-inflammation and periodontium regeneration, which provides a great potential candidate for periodontitis treatment in the dental clinic. Statement of Significance To terminate the alveolar bone resorption caused by periodontitis, simultaneous anti-inflammation and periodontium regeneration is required, which has not appeared in the existing methods. Here, (1) the chitosan (CS)/ß-sodium glycerophosphate/gelatin hydrogels loaded with aspirin/erythropoietin (EPO) can form at body temperature in 5 min with excellent biocompatibility in vitro and in vivo; (2) The faster release of aspirin than EPO in the early stage is beneficial for anti-inflammation and provides a microenvironment for ensuring the regeneration function of EPO in the following step. In vivo experiments revealed that the hydrogels are effective in the control of inflammation and regeneration of the periodontium. These results indicate that our synthesized hydrogels have a great potential in the future clinical application.

[Polarity of ameloblasts and odontoblasts and their related regulators].

The polarity of ameloblasts and odontoblasts is crucial for their differentiation and function. Polarity-related molecules play an important role in this process. This review summarizes the process of polarity formation of ameloblasts and odontoblasts and their related regulators.

[The role of bone morphogenetic protein signaling pathway in tooth root development].

The bone morphogenetic protein (BMP) family is an important factor in the regulation of cell ular life activities and in the development of almost all tissues. BMP-mediated signaling plays an important role in tooth root development, which is a part of tooth development. Epithelial and mesenchymal interactions are involved in tooth root development, but the BMP signaling pathway has a different effect on tooth root development in epithelial and mesenchymal. This review summarizes the advances of BMP signaling in tooth root development.

ACVR1 is essential for periodontium development and promotes alveolar bone formation.

OBJECTIVE: To explore the role of a BMP type I receptor (ACVR1) in regulating periodontium development, Acvr1 was conditionally disrupted in Osterix-expressing cells. METHODS: Mandibles from both control (Acvr1 fx/+; Osterix-Cre (+)/(-)) and cKO (Acvr1 fx/-; Osterix-Cre (+)/(-)) mice at postnatal day 21 (PN21) were scanned by micro-CT, followed by decalcification and histological observations. Distributions and levels of differentiation markers of fibroblasts, osteoblasts and cementocytes in the periodontium were detected by immunohistochemical (IHC) staining. RESULTS: Micro-CT results showed that bone mass and bone mineral density of the alveolar bones in the cKO mice were lower than those in the controls. Histomorphometry within the alveolar bones revealed that the lower bone mass observed in the cKO mice was caused by increased numbers and resorption activities of osteoclasts. The markers for osteoblast differentiation, Col I and DMP1, were reduced and the signals of the RANKL/OPG ratio were increased in the alveolar bones of the cKO mice compared to those of the control mice. The periodontal ligament in the cKO mice exhibited disorganized collagen fibers with weaker signals of Col I and periostin. However, there was no difference in terms of the cellular cementum between the two groups. CONCLUSION: ACVR1 is essential for normal periodontium development. ACVR1 in the osteoblasts negatively regulates osteoclast differentiation in association with the RANKL/OPG axis and thus promotes alveolar bone formation.