Natural compound phloretin restores periodontal immune homeostasis via HIF-1α-regulated PI3K/Akt and glycolysis in macrophages.

Periodontitis is a chronic inflammatory disease that affects about 45 %-50 % of adults worldwide, but the efficacy of current clinical therapies is unsatisfactory due to the complicated periodontal immune microenvironment. Thus, developing drugs that can regulate innate immune cells (e.g., macrophages) is a potent strategy to treat periodontitis. Here, we report that phloretin, a food plant-derived natural compound, is sufficient to alleviate periodontitis through immune regulation. In vivo, phloretin treatment could significantly reduce alveolar bone resorption and periodontal inflammation in mouse periodontitis models. In vitro, phloretin could suppress proinflammatory (M1-like) polarization and cytokine release in macrophages induced by LPS. Mechanistically, the immune regulatory role of phloretin in macrophages may be due to its metabolic regulation effect. Phloretin might restore the balance of M1/M2 macrophage transition in periodontitis by inhibiting HIF-1α-mediated glycolysis and PI3k/Akt pathways, thereby reducing the proinflammatory effect and immune disorder caused by over-activated M1 macrophages. Together, this study highlights that natural compound, such as phloretin, can restore periodontal immune homeostasis by metabolic regulation of macrophages, which may provide novel insight into the treatment of periodontitis.

ECM-Mimicking Strontium-Doped Nanofibrous Microspheres for Periodontal Tissue Regeneration in Osteoporosis.

Regenerating periodontal defects in osteoporosis patients presents a significant clinical challenge. Unlike the relatively straightforward regeneration of homogeneous bone tissue, periodontal regeneration requires the intricate reconstruction of the cementum-periodontal ligament-alveolar bone interface. Strontium (Sr)-doped biomaterials have been extensively utilized in bone tissue engineering due to their remarkable pro-osteogenic attributes. However, their application in periodontal tissue regeneration has been scarcely explored. In this study, we synthesized an innovative injectable Sr-BGN/GNM scaffold by integrating Sr-doped bioactive glass nanospheres (Sr-BGNs) into the nanofiber architecture of gelatin nanofiber microspheres (GNMs). This design, mimicking the natural bone extracellular matrix (ECM), enhanced the scaffold's mechanical properties and effectively controlled the sustained release of Sr ions (Sr2+), thereby promoting the proliferation, osteogenic differentiation, and ECM secretion of PDLSCs and BMSCs, as well as enhancing vascularization in endothelial cells. In vivo experiments further indicated that the Sr-BGNs/GNMs significantly promoted osteogenesis and angiogenesis. Moreover, the scaffold's tunable degradation kinetics optimized the prolonged release and pro-regenerative effects of Sr2+ in vivo, matching the pace of periodontal regeneration and thereby facilitating the regeneration of functional periodontal tissues under osteoporotic conditions. Therefore, Sr-BGNs/GNMs emerge as a promising candidate for advancing periodontal regeneration strategies.

[Research Progress in the Regulatory Role of circRNA-miRNA Network in Bone Remodeling]. / circRNA-miRNAç½‘ç»œè°ƒæŽ§éª¨é‡å¡‘çš„ç ”ç©¶è¿›å±•.

The dynamic balance between bone formation and bone resorption is a critical process of bone remodeling. The imbalance of bone formation and bone resorption is closely associated with the occurrence and development of various bone-related diseases. Under both physiological and pathological conditions, non-coding RNAs (ncRNAs) play a crucial regulatory role in protein expression through either inhibiting mRNAs translation or promoting mRNAs degradation. Circular RNAs (circRNAs) are a type of non-linear ncRNAs that can resist the degradation of RNA exonucleases. There is accumulating evidence suggesting that circRNAs and microRNAs (miRNAs) serve as critical regulators of bone remodeling through their direct or indirect regulation of the expression of osteogenesis-related genes. Additionally, recent studies have revealed the involvement of the circRNAs-miRNAs regulatory network in the process by which mesenchymal stem cells (MSCs) differentiate towards the osteoblasts (OB) lineage and the process by which bone marrow-derived macrophages (BMDM) differentiate towards osteoclasts (OC). The circRNA-miRNA network plays an important regulatory role in the osteoblastic-osteoclastic balance of bone remodeling. Therefore, a thorough understanding of the circRNA-miRNA regulatory mechanisms will contribute to a better understanding of the regulatory mechanisms of the balance between osteoblastic and osteoclastic activities in the process of bone remodeling and the diagnosis and treatment of related diseases. Herein, we reviewed the functions of circRNA and microRNA. We also reviewed their roles in and the mechanisms of the circRNA-miRNA regulatory network in the process of bone remodeling. This review provides references and ideas for further research on the regulation of bone remodeling and the prevention and treatment of bone-related diseases.

Long non-coding RNA LncTUG1 regulates favourable compression force-induced cementocytes mineralization via PU.1/TLR4/SphK1 signalling.

Orthodontic tooth movement (OTM) is a highly coordinated biomechanical response to orthodontic forces with active remodelling of alveolar bone but minor root resorption. Such antiresorptive properties of root relate to cementocyte mineralization, the mechanisms of which remain largely unknown. This study used the microarray analysis to explore long non-coding ribonucleic acids involved in stress-induced cementocyte mineralization. Gain- and loss-of-function experiments, including Alkaline phosphatase (ALP) activity and Alizarin Red S staining, quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, and immunofluorescence analyses of mineralization-associated factors, were conducted to verify long non-coding ribonucleic acids taurine-upregulated gene 1 (LncTUG1) regulation in stress-induced cementocyte mineralization, via targeting the Toll-like receptor 4 (TLR4)/SphK1 axis. The luciferase reporter assays, chromatin immunoprecipitation assays, RNA pull-down, RNA immunoprecipitation, and co-localization assays were performed to elucidate the interactions between LncTUG1, PU.1, and TLR4. Our findings indicated that LncTUG1 overexpression attenuated stress-induced cementocyte mineralization, while blocking the TLR4/SphK1 axis reversed the inhibitory effect of LncTUG1 on stress-induced cementocyte mineralization. The in vivo findings also confirmed the involvement of TLR4/SphK1 signalling in cementocyte mineralization during OTM. Mechanistically, LncTUG1 bound with PU.1 subsequently enhanced TLR4 promotor activity and thus transcriptionally elevated the expression of TLR4. In conclusion, our data revealed a critical role of LncTUG1 in regulating stress-induced cementocyte mineralization via PU.1/TLR4/SphK1 signalling, which might provide further insights for developing novel therapeutic strategies that could protect roots from resorption during OTM.

The onset of adenosine monophosphate-activated protein kinase activity on orthodontic tooth movement in rats with type 2 diabetes.

Adenosine monophosphate-activated protein kinase (AMPK) plays pivotal roles in metabolic diseases including type 2 diabetes. However, the specific role of AMPK for orthodontic tooth movement in type 2 diabetes is unclear. In this study, a diabetic rat model was established through dietary manipulation and streptozocin injection. Examinations were conducted to select qualified type 2 diabetic rats. Then, an orthodontic device was applied to these rats for 0, 3, 7, or 14 days. The distance of orthodontic tooth movement and parameters of alveolar bone were analyzed by micro-computed tomography. Periodontal osteoclastic activity, inflammatory status, and AMPK activity were measured via histological analyses. Next, we repeated the establishment of diabetic rats to investigate whether change of AMPK activity was associated with orthodontic tooth movement under type 2 diabetes. The results showed that diabetic rats exhibited an exacerbated alveolar bone resorption, overactive inflammation, and decreased periodontal AMPK activity during orthodontic tooth movement. Injection of the AMPK agonist alleviated type 2 diabetes-induced periodontal inflammation and alveolar bone resorption, thus normalizing distance of orthodontic tooth movement. Our study indicates that type 2 diabetes decreases periodontal AMPK activity, leading to excessive inflammation elevating osteoclast formation and alveolar bone resorption, which could be reversed by AMPK activation.

The mechanism underlying the remodeling effect of lactoferrin on midpalatal sutures during maxillary expansion and relapse in rats.

INTRODUCTION: The remodeling effects of intragastric administration and intramaxillary injection of lactoferrin (LF) on midpalatal sutures (MPS) during maxillary expansion and relapse in rats were studied to explore the underlying bone remodeling mechanism. METHODS: Using a rat model of maxillary expansion and relapse, rats were treated with LF by intragastric administration (1 g·kg-1·d-1) or intramaxillary injection (5 mg·25 µl-1·d-1). The effects of LF on the osteogenic and osteoclast activities of MPS were observed by microcomputed tomography, histologic staining, and immunohistochemical staining, and the expressions of key factors in the extracellular regulated protein kinase 1/2 (ERK1/2) pathway and osteoprotegerin (OPG)-receptor activator of nuclear factor-KB ligand (RANKL)-receptor activator of nuclear factor-KB (RANK) axis were detected. RESULTS: Compared with the group with maxillary expansion alone, osteogenic activity was relatively enhanced, whereas osteoclast activity was relatively weakened in the groups administered LF, and the phosphorylated-ERK1/2: ERK1/2 and OPG: RANKL expression ratios increased significantly. The difference was more significant in the group administered LF intramaxillary. CONCLUSIONS: Administration of LF promoted osteogenic activity at MPS and inhibited osteoclast activity during maxillary expansion and relapse in rats, which may have occurred through regulation of the ERK1/2 pathway and the OPG-RANKL-RANK axis. The efficiency of intramaxillary LF injection was greater than that of intragastric LF administration.

Engineered Plant Virus Complexes with a RANK Motif Modulator and Bone Targeting for Osteoporosis Treatment.

Osteoporosis is a systemic skeletal disorder characterized by excessive osteoclastic bone resorption and impaired osteoblastic bone formation. Traditional delivery of antiresorptive drugs lacks a specific biodistribution in the body and may cause adverse effects to the patients. In this study, the peptide BTRM is first synthesized consisting of the bone-targeting peptide Asp8 (BT) and the peptide derived from the amino acid sequences of RANK Motif2/3 (RM), two cytoplasmic RANK motifs (PVQEET560-565 and PVQEQG604-609) that have been reported to play an important role in osteoclastogenesis. Then, BTRM is conjugated on the plant virus-like nanoparticles (VNPs) obtained from cowpea chlorotic mottle viruses (CCMVs), forming the engineered plant viruses BTRM-VNPs. In vitro experiments demonstrate that BTRM-VNPs can effectively and safely inhibit osteoclast differentiation and function. Moreover, after injection into ovariectomized mice, BTRM-VNPs show excellent capability to target bone tissue and improve osteoporotic bone loss. Collectively, the findings may provide a novel and promising strategy in the treatment of osteoporotic defects via targeting bone tissue and regulating the function of RANK Motif2/3.

Cyclic di-adenosine monophosphate regulates the osteogenic and adipogenic differentiation of hPDLSCs via MAPK and NF-κB signaling.

Cyclic di-adenosine monophosphate (c-di-AMP) is a bacterial second messenger that can be recognized by infected host cells and activate the immunoinflammatory response. The purpose of this study is to demonstrate the effect of c-di-AMP on the differentiation of human periodontal ligament stem cells (hPDLSCs) and its underlying mechanisms. In the present study, we find that the gingival crevicular fluid (GCF) of patients with chronic periodontitis has a higher expression level of c-di-AMP than that of healthy people. In vitro, c-di-AMP influences the differentiation of hPDLSCs by upregulating Toll-like receptors (TLRs); specifically, it inhibits osteogenic differentiation by activating NF-κB and ERK/MAPK and promotes adipogenic differentiation through the NF-κB and p38/MAPK signaling pathways. Inhibitors of TLRs or activated pathways reduce the changes induced by c-di-AMP. Our results establish the potential correlation among bacterial c-di-AMP, periodontal tissue homeostasis and chronic periodontitis pathogenesis.

Computer-aided surgical workflow in a surgery - First orthognathic approach to correct anterior open bite in a young adult with temporomandibular disorders.

An 18-year-old female patient with temporomandibular disorders (TMD) history sought medical care in orthodontic-orthognathic interdisciplinary department with chief complaint of anterior open bite. After splint therapy to seat the condylar into the musculo-skeletally stable position, a surgery-first approach was formulated assisted by 3D virtual planning and transferred to the surgery by computer-aided manufacturing splint. No TMD symptom reoccurrence was reported or noted. Stable occlusion and satisfactory facial aesthetics were achieved. In the 18-month follow-up, no clinically significant open bite relapse occurred. This case report describes the remarkable role that computer-assisted surgical simulation could play throughout the surgical-orthodontic procedure to correct the skeletal open bite deformity.

Connective tissue growth factor promotes cell-to-cell communication in human periodontal ligament stem cells via MAPK and PI3K pathway.

BACKGROUND: Cell-cell communication is an essential process to respond to biological stimuli and sustain the micro environmental homeostasis of human periodontal ligament stem cells (hPDLSCs). Connective tissue growth factor (CTGF), a critical secreted matrix protein, exhibits significant tasks in regulating the cell-cell and cell-matrix interactions. This study aimed to explore the relationship between CTGF and cell communication and the underlying mechanism. METHODS: qRT-PCR was used to detect CCN family, connexin, and pannexin family expression in hPDLSCs. Stimulation with CTGF, cell migration assay was performed to examine the wound repair. The scrape loading/dye transfer assay was employed to access lucifer Yellow molecules transfer efficiency mediated by cell-cell communication. Connexin43 (Cx43), Pannexin1 (Panx1), MAPK, and the PI3K/Akt signaling pathway proteins were examined via Western blotting. Immunofluorescence was applied to visualize the localization of specific proteins within cells. Corresponding pathway inhibitors were applied to hPDLSCs to detect Cx43, Panx1 expression, and intercellular communication induced by CTGF. RESULTS: Our result showed that CTGF was the second most expressed CCN family member in hPDLSCs. Cx43, and Panx1 were the most widely expressed gap junction hemichannels in hPDLSCs. CTGF enhanced hPDLSCs migration in a dose-dependent manner. CTGF promoted cell-cell communication by up-regulating Cx43 and Panx1. CTGF induced Akt, JNK, and p38 phosphorylation and subcellular relocation. Inhibiting corresponding pathways reduced Cx43 expression, thereby weakening CTGF-induced cell-cell communication. However, the Panx1 expression in CTGF-treated hPDLSCs mainly depended on PI3K/Akt signaling. CONCLUSION: We provided novel evidence that CTGF promoted cell-cell communication in hPDLSCs through MAPK and PI3K pathway.

CTGF facilitates cell-cell communication in chondrocytes via PI3K/Akt signalling pathway.

PURPOSES: Gap junction intercellular communication (GJIC) is essential for articular cartilage to respond appropriately to physical or biological stimuli and maintain homeostasis. Connective tissue growth factor (CTGF), identified as an endochondral ossification genetic factor, plays a vital role in cell proliferation, migration and adhesion. However, how CTGF regulates GJIC in chondrocytes is still unknown. This study aims to explore the effects of CTGF on GJIC in chondrocytes and its potential biomechanism. MATERIALS AND METHODS: qPCR was performed to determine the expression of gene profile in the CCN family in chondrocytes. After CTGF treatment, CCK-8 assay and scratch assay were performed to explore cell proliferation and migration. A scrape loading/dye transfer assay was adopted to visualize GJIC in living chondrocytes. Western blot analysis was done to detect the expression of Cx43 and PI3K/Akt signalling. Immunofluorescence staining was used to show protein distribution. siRNA targeting CTGF was used to detect the influence on cell-cell communication. RESULTS: The CTGF (CCN2) was shown to be the highest expressed member of the CCN family in chondrocytes. CTGF facilitated functional gap junction intercellular communication in chondrocytes through up-regulation of Cx43 expressions. CTGF activated PI3K/Akt signalling to promote Akt phosphorylation and translocation. Suppressing CTGF also reduced the expression of Cx43. The inhibition of PI3K/Akt signalling decreased the expressions of Cx43 and thus impaired gap junction intercellular communication enhanced by CTGF. CONCLUSIONS: For the first time, we provide evidence to show CTGF facilitates cell communication in chondrocytes via PI3K/Akt signalling pathway.

Intermittent parathyroid hormone promotes cementogenesis via ephrinB2-EPHB4 forward signaling.

Intermittent parathyroid hormone (PTH) promotes periodontal repair, but the underlying mechanisms remained unclear. Recent studies found that ephrinB2-EPHB4 forward signaling mediated the anabolic effect of PTH in bone homeostasis. Considering the similarities between cementum and bone, we aimed to examine the therapeutic effect of PTH on resorbed roots and explore the role of forward signaling in this process. In vivo experiments showed that intermittent PTH significantly accelerated the regeneration of root resorption and promoted expression of EPHB4 and ephrinB2. When the signaling was blocked, the resorption repair was also delayed. In vitro studies showed that intermittent PTH promoted the expression of EPHB4 and ephrinB2 in OCCM-30 cells. The effects of PTH on the mineralization capacity of OCCM-30 cells was mediated through the ephrinB2-EPHB4 forward signaling. These results support the premise that the anabolic effects of intermittent PTH on the regeneration of root resorption is via the ephrinB2-EPHB4 forward signaling pathway.

Long noncoding RNA expression profiles in intermittent parathyroid hormone induced cementogenesis.

The aim of this study was to explore the involvement of long noncoding RNAs (lncRNAs) during intermittent parathyroid hormone (PTH) induced cementogenesis. Expression profiles of lncRNAs and mRNAs were obtained using high-throughput microarray. Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and coding-noncoding gene coexpression networks construction were performed. We identified 190 lncRNAs and 135 mRNAs that were differentially expressed during intermittent PTH-induced cementogenesis. In this process, the Wnt signaling pathway was negatively regulated, and eight lncRNAs were identified as possible core regulators of Wnt signaling. Based on the results of microarrray analysis, we further verified the repressed expression of Wnt signaling crucial components ß-catenin, APC and Axin2. Above all, we speculated that lncRNAs may play important roles in PTH-induced cementogenesis via the negative regulation of Wnt pathway.

[The Study of Signal Pathway Regulating the Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells].

Osteogenesis of mesenchymal stem cells to differentiate between bone marrow by multiple signaling pathways that control, directly or indirectly affect small related transcription factor 2 (runt-related transcription factor 2, Runx2) and osteoblast specific transcription factor (osterix, Osx), the expression of osteogenesis key transcription factors, such as in the development and regeneration of the bone, bone repair has played a key role in the process of reconstruction. These pathways play their mechanism of action, but also intertwined associated constitute a complex signal transduction network, but due to the limitations of research methods, the osteogenic differentiation related signaling pathways of the specific mechanism is still unclear, if you can clarify these different signaling pathways play to the role of their relevant mechanism and the relationship between various pathways and the mechanism study of osteogenesis differentiation is of great importance. This article will review the progress of various signaling pathways in the regulation of osteogenic differentiation of bone marrow mesenchymal stem cells.

[Screen and Function Study of the Key Regulative Odontogenic Genes in Mice].

OBJECTIVE: To screen the key odontogenic genes in mice and verify the odontogenic inducing effect on amniotic epithelial cells (WISH). METHODS: The spatially and temporally different expression of bone morphogenetic proteins 4 (BMP4), fibroblast growth factor 8 (FGF8), sonic hedgehog (SHH), lymphoid enhancer factor 1 (LEF1) proteins and their genes expression in the early odontogenesis stage (embryo day 10.5 (E10.5)、E11.5、E14.5) in fetal mice were detected by immunohistochemistry staining and quantitative real-time PCR (RT-qPCR). According to the results, we screened the probable key odontogenic genes. Then adding osteogenic inducing solution to induce non-odontogenic epithelium cells, WISH. After 3 weeks culture of non-odontogenic epithelial WISH for osteogenic induction, the epithelial-mesenchymal transformation cap ability was evaluated by using Alizarin (ALZ) red staining and RT-qPCR on the alkaline phosphatase ( ALP) mRNA expression level. Using germ layer recombination experiment to observe and verify whether the screened genes can induce non-odontogenic epithelium cells acquire odontogenesis ability. The recombined tissue grafts containing key genes were transplanted beneath the renal capsule of mice. RESULTS: The results of immunohistochemistry staining and RT-qPCR showed that on E10.5 BMP4 protein and gene were differently expressed in the first and second branchial arch epithelium, which synchronized the odontogenic capability transferring from epithelium to mesenchyme from E10.5-E14.5. Though the expression of FGF8 protein and gene existed such difference in the first and second branchial arch epithelium, there was no synchronization in transfer. The expression of LEF1 and SHH proteins and genes had neither difference nor synchronization. So far, we considered the BMP4 was the probable key odontogenic gene. Through 3 weeks' osteogenic induction, ALZ red stained positively and calcium nodules were observed in WISH, and the expression level of ALP mRNA increased. In the germ layer recombination experiment, exogenous BMP4 protein enabled the second branchial arch mesenchyme forming tooth-like structures after recombined with the second branchial arch epithelium or WISH. CONCLUSIONS: The proteins and genes of BMP4, FGF8, SHH and LEF1 are spatially and temporally differently expressed in the early tooth development stage in mice. The protein and gene of BMP4 are differently expressed between the first and second branchial arch epithelium and enables the non-odontogenic epithelium acquiring odontogenic ability. BMP4 is the possible key odontogenic gene.

Effects of estrogen on root repair after orthodontically induced root resorption in ovariectomized rats.

INTRODUCTION: This study aimed to investigate the effects of estrogen on root repair after orthodontically induced root resorption. METHODS: Seventy-two 6-week-old female Wistar rats were randomly divided into 3 groups: ovariectomy only (OVX), ovariectomy plus estradiol injection (OVX + E2), and sham operation (control). E2 was administrated to all the experimental animals after the establishment of the root repair model. One-way analysis of variance with the Tukey post-hoc test was used to analyze the experimental results. RESULTS: Micro-computed tomography and hematoxylin and eosin staining showed that the total volumes of resorption lacunae were significantly smaller in the control and OVX + E2 groups than those in the OVX group. Alkaline phosphatase and tartrate-resistant acid phosphatase stainings suggested that the cementoblastic activities and the amount of new cementum formation were inhibited while the activities of osteoclasts were obvious in the OVX group. The immunohistochemistry stainings revealed that the osteoprotegerin to receptor activator of nuclear factor-кB ligand ratio and the phosphorylated extracellular signal-regulated kinases to extracellular signal-regulated kinases ratio of the control and OVX + E2 groups were significantly greater than those of the OVX group. CONCLUSIONS: These findings demonstrated that estrogen administration might be a solution to reduce orthodontically induced root resorption through the activation of extracellular signal-regulated kinase-1/2 pathway and enhancement of cementogenesis.

AFF4 enhances odontogenic differentiation of human dental pulp cells.

AFF4 is a component of super elongation complex (SECs) and functions as a scaffold protein to bridge the transcription elongation factors. It is associated with leukemia, HIV transcription, and head neck cancer. However, its role in odontogenic differentiation of dental pulp cells (DPCs) is unclear. Here, we show the expression of AFF4 is increased during odontogenesis. Depletion of AFF4 in human DPCs leads to a decrease of alkaline phosphatase (ALP) activity, calcium mineralization and odontogenic-related genes expression. On the contrary, Lentivirus-mediated overexpression of AFF4 induces the odontogenic potential of DPCs. Mechanistically, we found AFF4 regulates the transcription of NFIC, a key factor for tooth root formation. Overexpression of NFIC successfully rescues the restricted differentiation of AFF4-depleted cells. Our data demonstrate that AFF4 serves as a previously unknown regulator of odontogenesis.

Enhancing osseointegration of titanium implants through large-grit sandblasting combined with micro-arc oxidation surface modification.

PURPOSE: The demand for titanium dental implants has risen sharply. However, the clinical success rate of implant surgery needs to be improved. In this paper, we report a novel surface modification strategy, large-grit sandblasting combined with micro-arc oxidation (SL-MAO), aiming to promote peri-implant bone formation and osseointegration of titanium implants. MATERIALS AND METHODS: Modified titanium samples were prepared by large-grit sandblasting and acid etching (SLA), micro-arc oxidation (MAO), and SL-MAO. The resulting topographical changes and chemical composition of the samples were examined by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS), respectively, and the biocompatibility and bioactivity were analyzed by bone-marrow mesenchymal stem cells (BMMSC) adhesion tests. Modified titanium implants were also inserted into the femurs of beagle dogs, and their competence of osseointegration was appraised by quantitative histomorphometry and micro-computed-tomography (micro-CT) analyses. RESULTS: Compared to SLA and MAO techniques, SL-MAO surface modification further enhanced titanium surfaces by creating a topographic morphology characterized by both micron-sized craters and sub-micron-scale pits, and resulted in superior chemical composition, which promoted cell adhesion, proliferation, and osteogenic differentiation. SL-MAO-modified titanium implants osseointegrated more efficiently than SLA or MAO controls, with significantly higher bone-area (BA) ratio and bone-implant contact (BIC) in the peri-implant region. CONCLUSIONS: The SL-MAO surface modification technique optimized the surface properties of titanium implants and enhanced peri-implant bone formation and osseointegration.

Parathyroid hormone-related peptide (1-34) promotes tooth eruption and inhibits osteogenesis of dental follicle cells during tooth development.

Dental follicle cells (DFCs) activate and recruit osteoclasts for tooth development and tooth eruption, whereas DFCs themselves differentiate into osteoblasts to form alveolar bone surrounding tooth roots through the interaction with Hertwig's epithelial root sheath (HERS). Also during tooth development, parathyroid hormone-related peptide (PTHrP) is expressed surrounding the tooth germ. Thus, we aimed to investigate the effect of PTHrP (1-34) on bone resorption and osteogenesis of DFCs in vitro and in vivo. In vitro studies demonstrated that DFCs cocultured with HERS cells expressed higher levels of BSP and OPN than the DFCs control group, whereas cocultured DFCs treated with PTHrP (1-34) had lower expressions of ALP, RUNX2, BSP, and OPN than the cocultured DFCs control group. Moreover, we found PTHrP (1-34) inhibited osteogenesis of cocultured DFCs by inactivating the Wnt/ß-catenin pathway. PTHrP (1-34) also increased the expression of RANKL/OPG ratio in DFCs. Consistently, in vivo study found that PTHrP (1-34) accelerated tooth eruption and inhibited alveolar bone formation. Therefore, these results suggest that PTHrP (1-34) accelerates tooth eruption and inhibits osteogenesis of DFCs by inactivating Wnt/ß-catenin pathway.

Insights into the roles of lncRNAs in skeletal and dental diseases.

Long noncoding RNAs (lncRNAs) are a class of non-protein-coding transcripts with the length longer than 200 nucleotides. Growing evidence suggests that lncRNAs, which were initially thought to be merely transcriptional "noise", participate in a wide repertoire of biological processes. It has been well established that lncRNAs not only play important roles in genomic regulation, transcription, posttranscriptional processes but are also implicated in the pathogenesis of human diseases including cardiovascular diseases, diabetes, neurodegenerative disorders, and cancer. However, the pathological role of lncRNAs in skeletal and dental diseases is just beginning to be uncovered. In the present review, we outline the current understanding of the established functions and underlying mechanisms of lncRNAs in various cellular processes. Furthermore, we discuss new findings on the role of lncRNAs in osteoblastogenesis and osteoclastogenesis as well as their involvement in skeletal and dental diseases. This review intends to provide a general framework for the actions of lncRNAs and highlight the emerging evidence for the functions of lncRNAs in skeletal and dental diseases.