Advances in the relationship between periodontopathogens and respiratory diseases (Review).

Periodontitis is a common chronic inflammatory and destructive disease in the mouth and is considered to be associated with systemic diseases. Accumulating evidence has suggested that periodontitis is a risk factor for pulmonary diseases such as pneumonia, chronic obstructive pulmonary disease (COPD), asthma, coronavirus disease 2019 (COVID­19) and lung cancer. The presence of common periodontal pathogens has been detected in samples from a variety of pulmonary diseases. Periodontal pathogens can be involved in lung diseases by promoting the adhesion and invasion of respiratory pathogens, regulating the apoptosis of respiratory epithelium and inducing overexpression of mucin and disrupting the balance of immune systemin respiratory epithelium cells. Additionally, measures to control plaque and maintain the health of periodontal tissue can decrease the incidence of respiratory adverse events. This evidence suggests a close association between periodontitis and pulmonary diseases. The present study aimed to review the clinical association between periodontitis and pneumonia, COPD, asthma, COVID­19 and lung cancer, and propose a possible mechanism and potential role of periodontal pathogens in linking periodontal disease and lung disease. This could provide a direction for further research on the association between periodontitis and lung disease and provide novel ideas for the clinical diagnosis and treatment management of these two diseases.

Advanced nanozymes possess peroxidase-like catalytic activities in biomedical and antibacterial fields: review and progress.

Infectious diseases caused by bacterial invasions have imposed a significant global health and economic burden. More worryingly, multidrug-resistant (MDR) pathogenic bacteria born under the abuse of antibiotics have further escalated the status quo. Nowadays, at the crossroads of multiple disciplines such as chemistry, nanoscience and biomedicine, nanozymes, as enzyme-mimicking nanomaterials, not only possess excellent bactericidal ability but also reduce the possibility of inducing resistance. Thus, nanozymes are promising to serve as an alternative to traditional antibiotics. Nanozymes that mimic peroxidase (POD) activity are also known as POD nanozymes. In recent years, POD nanozymes have become one of the most frequently reported and effective nanozymes due to their broad-spectrum bactericidal properties and unique sterilization mechanism. In this review, we introduce the mechanism as well as the classification of POD nanozymes. More importantly, to further improve the antibacterial efficacy of POD nanozymes, we elaborate on three aspects: (1) improving the physicochemical properties; (2) regulating the catalytic microenvironment; and (3) designing multimodel POD nanozymes. In addition, we review the nanosafety of POD nanozymes for discussing their potential toxicity. Finally, the remaining challenges of POD nanozymes and possible future directions are discussed. This work provides a systematic summary of POD nanozymes and hopefully contributes to the early clinical translation.

Naringin-induced M2 macrophage polarization facilitates osteogenesis of BMSCs and improves cranial bone defect healing in rat.

Osteoimmunology has uncovered the critical role of the immune microenvironment in the bone healing process, with macrophages playing a central part in generating immune responses via chemokine production. Naringin, a flavanone glycoside extracted from various plants, has been shown to promote osteoblast differentiation, thereby enhancing bone formation and mitigating osteoporosis progression. Current research on the osteogenic mechanism primarily focuses on the direct impact of naringin on mesenchymal stem cells, while its indirect immunoregulatory effects remain elusive. In this study, we investigated the bone defect-enhancing effects of varying naringin concentrations in vivo using a cranial bone defect model in Sprague-Dawley rats. We assessed the osteoimmune modulation capacity of naringin by exposing lipopolysaccharide (LPS)-induced RAW 264.7 macrophages to different doses of naringin. To further elucidate the underlying osteogenic enhancement mechanism, Bone Marrow Stromal Cells (BMSCs) derived from mice were treated with conditioned media from naringin-treated macrophages. Our findings indicated that naringin promotes M2 phenotype polarization in macrophages, as evidenced by the downregulation of pro-inflammatory cytokines Inducible Nitric Oxide Synthase (iNOS), interleukin (IL)-1ß, and Tumor Necrosis Factor (TNF)-α, and the upregulation of anti-inflammatory cytokine Transforming growth factor (TGF)-ß. Transcriptome analysis revealed that differentially expressed genes were significantly enriched in osteoblast differentiation and anti-inflammatory response pathways in naringin-pretreated macrophages, with the cytokines signaling pathway being upregulated. The conditioned media from naringin-treated macrophages stimulated the expression of osteogenic-related genes Alkaline phosphatase (Alp), osteocalcin (Ocn), osteopontin (Opn), and Runt-related transcription factor (Runx) 2, as well as protein expression in BMSCs. In conclusion, naringin alleviates macrophage inflammation by promoting M2 phenotype polarization, which in turn enhances the osteogenic differentiation of BMSCs, contributing to its bone healing effects in vivo. These results suggest that naringin holds significant potential for improving bone defect healing through osteoimmune modulation.

Isoliquiritin treatment of osteoporosis by promoting osteogenic differentiation and autophagy of bone marrow mesenchymal stem cells.

Osteoporosis is a chronic progressive bone disease characterized by the decreased osteogenic ability of osteoblasts coupled with increased osteoclast activity. Natural products showing promising therapeutic potential for postmenopausal osteoporosis remain underexplored. In this study, we aimed to analyze the therapeutic effects of isoliquiritin (ISL) on osteoporosis in mice and its possible mechanism of action. An ovariectomy-induced osteoporosis mouse model and bone marrow mesenchymal stem cells (BMSCs) were used to analyze the effects of ISL on bone regeneration in vivo and in vitro, respectively. Mitogen-activated protein kinase (MAPK) and autophagy inhibitors were used, to investigate whether the MAPK signaling pathway and autophagy affect the osteogenic differentiation of BMSCs. ISL significantly improved bone formation and reduced bone resorption in mouse femurs without inducing any detectable toxicity in critical organs such as the liver, kidney, brain, heart, and spleen. In vitro experiments showed that ISL enhanced the proliferation and osteogenic differentiation of BMSCs and that its osteogenic effect was attenuated by p38/extracellular regulated protein kinase (ERK) and autophagy inhibitors. Further studies showed that the inhibition of phosphorylated p38/ERK blocked ISL autophagy in BMSCs. ISL promoted the osteogenic differentiation of BMSCs through the p38/ERK-autophagy pathway and was therapeutically effective in treating osteoporosis in ovariectomized mice without any observed toxicity to vital organs. These results strongly suggest the promising potential of ISL as a safe and efficacious candidate drug for the treatment of osteoporosis.

Multifunctional Lithium-Doped Mesoporous Nanoparticles for Effective Dentin Regeneration in vivo.

Introduction: Effective infection control without irritating the pulp tissue is the key to successful vital pulp therapy. Developing a novel antibacterial biomaterial that promotes dentin regeneration for pulp capping is thus a promising strategy for enhancing vital pulp therapy. Methods: Lithium-doped mesoporous nanoparticles (Li-MNPs) were synthesized using an alkali-catalyzed sol-gel method. The particle size, elemental distribution, surface morphology, pore structure, and ion release from Li-MNPs were measured. Human dental pulp stem cells (hDPSCs) and Streptococcus mutans (S. mutans) were used to evaluate the biological effects of Li-MNPs. In addition, a dental pulp exposure mouse model was used to evaluate the regenerative effects of Li-MNPs. Results: Li-MNPs had a larger surface area (221.18 m2/g), a larger pore volume (0.25 cm3/g), and a smaller particle size (520.92 ± 35.21 nm) than MNPs. The in vitro investigation demonstrated that Li-MNPs greatly enhanced the biomineralization and odontogenic differentiation of hDPSCs through the Wnt/ß-catenin signaling pathway. Li-MNPs showed a strong antibacterial effect on S. mutans. As expected, Li-MNPs significantly promoted dentin regeneration in situ and in vivo. Conclusion: Li-MNPs promoted dentin regeneration and inhibited S. mutans growth, implying a possible application as a pulp capping agent in vital pulp therapy.

Roles of extracellular vesicles on macrophages in inflammatory bone diseases.

Inflammatory bone disease is a general term for a series of diseases caused by chronic inflammation, which leads to the destruction of bone homeostasis, that is, the osteolytic activity of osteoclasts increases, and the osteogenic activity of osteoblasts decreases, leading to osteolysis. Macrophages are innate immune cell with plasticity, and their polarization is related to inflammatory bone diseases. The dynamic balance of macrophages between the M1 phenotype and the M2 phenotype affects the occurrence and development of diseases. In recent years, an increasing number of studies have shown that extracellular vesicles existing in the extracellular environment can act on macrophages, affecting the progress of inflammatory diseases. This process is realized by influencing the physiological activity or functional activity of macrophages, inducing macrophages to secrete cytokines, and playing an anti-inflammatory or pro-inflammatory role. In addition, by modifying and editing extracellular vesicles, the potential of targeting macrophages can be used to provide new ideas for developing new drug carriers for inflammatory bone diseases.

Exosomes derived from odontogenic stem cells: Its role in the dentin-pulp complex.

Odontogenic stem cells originate from cranial neural crest cells and offer unique advantages in the regeneration of dentin-pulp complex. There is increasing evidence that stem cells exert their biological functions mainly through exosome-based paracrine effects. Exosomes contain DNA, RNA, proteins, metabolites, etc., which can play a role in intercellular communication and have similar therapeutic potential to stem cells. In addition, compared with stem cells, exosomes also have the advantages of good biocompatibility, high drug carrying capacity, easy to obtain, and few side effects. Odontogenic stem cell-derived exosomes mainly affect the regeneration of the dentin-pulp complex by regulating processes such as dentintogenesis, angiogenesis, neuroprotection and immunomodulation. This review aimed to describe "cell-free therapies" based on odontogenic stem cell-derived exosomes, which aim to regenerate the dentin-pulp complex.

Selenium-Doped Mesoporous Bioactive Glass Regulates Macrophage Metabolism and Polarization by Scavenging ROS and Promotes Bone Regeneration In Vivo.

Bone regeneration is complex and involves multiple cells and systems, with macrophage-mediated immune regulation being critical for the development and regulation of inflammation, angiogenesis, and osteogenesis. Biomaterials with modified physical and chemical properties (e.g., modified wettability and morphology) effectively regulate macrophage polarization. This study proposes a novel approach to macrophage-polarization induction and -metabolism regulation through selenium (Se) doping. We synthesized Se-doped mesoporous bioactive glass (Se-MBG) and demonstrated its macrophage-polarization regulation toward M2 and its enhancement of the macrophage oxidative phosphorylation metabolism. The underlying mechanism is the effective scavenging of excessive intracellular reactive oxygen species (ROS) by the Se-MBG extracts through the promotion of peroxide-scavenging enzyme glutathione peroxidase 4 expression in the macrophages; this, in turn, improves the mitochondrial function. Printed Se-MBG scaffolds were implanted into rats with critical-sized skull defects to evaluate their immunomodulatory and bone regeneration capacity in vivo. The Se-MBG scaffolds demonstrated excellent immunomodulatory function and robust bone regeneration capacity. Macrophage depletion with clodronate liposomes impaired the Se-MBG-scaffold bone regeneration effect. Se-mediated immunomodulation, which targets ROS scavenging to regulate macrophage metabolic profiles and mitochondrial function, is a promising concept for future effective biomaterials for bone regeneration and immunomodulation.

3D-printed gelatin/sodium alginate/58S bioactive glass scaffolds promote osteogenesis in vitro and in vivo.

Three-dimensional (3D)-printed scaffolds are a new strategy to fabricate biomaterials for treating bone defects. Here, using a 3D-printing technique, we fabricated scaffolds consisting of gelatin (Gel), sodium alginate (SA), and 58S bioactive glass (58S BG). To evaluate mechanical properties and biocompatibility of Gel/SA/58S BG scaffolds, the degradation test, compressive strength test, and cytotoxicity test were performed. The effect of the scaffolds on cell proliferation in vitro was determined by 4',6-diamidino-2-phenylindole (DAPI) staining. To evaluate osteoinductive properties, rBMSCs were cultured on the scaffolds for 7, 14, and 21 days and the expression of osteogenesis-related genes was analyzed using qRT-PCR. To examine the bone healing properties of Gel/SA/58S BG scaffolds in vivo, we used a rat mandibular critical-size defect bone model. The scaffolds were implanted into the defect area of rat mandible and bone regeneration and new tissue formation were assessed using microcomputed tomography (microCT) and hematoxylin and eosin (H&E) staining. The results showed that Gel/SA/58S BG scaffolds had appropriate mechanical strength as a filling material for bone defects. Furthermore, the scaffolds could be compressed within certain limits and then could recover their shape. The extract of the Gel/SA/58S BG scaffold showed no cytotoxicity. In vitro, the expression levels of Bmp2, Runx2, and OCN were increased in rBMSCs cultured on the scaffolds. In vivo, microCT and H&E staining demonstrated that scaffolds induced the formation of new bone at the mandibular defect area. These results indicated that Gel/SA/58S BG scaffolds have excellent mechanical characteristics, biocompatibility, and osteoinductive properties, suggesting that it could be a promising biomaterial for the repair of bone defects.

The role of PIWI-interacting RNA in naringin pro-angiogenesis by targeting HUVECs.

Angiogenesis is a biological process in which resting endothelial cells start proliferating, migrating and forming new blood vessels. Angiogenesis is particularly important in the repair of bone tissue defects. Naringin (NG) is the main active monomeric component of traditional Chinese medicine, which has various biological activities, such as anti-osteoporosis, anti-inflammatory, blood activation and microcirculation improvement. At present, the mechanism of naringin in the process of angiogenesis is not clear. PIWI protein-interacting RNA (piRNA) is a small noncoding RNA (sncRNA) that has the functions of regulating protein synthesis, regulating the structure of chromatin and the genome, stabilizing mRNA and others. Several studies have demonstrated that piRNAs can mediate the angiogenesis process. Whether naringin can interfere with the process of angiogenesis by regulating piRNAs and related target genes deserves further exploration. Thus, the purpose of this study was to validate the potential angiogenic and bone regeneration properties and related mechanisms of naringin both in vivo and in vitro.

Enhancing undergraduate research talents: the role of tutors in dental basic research education.

Purpose: This study endeavors to investigate ways to optimize the role of teachers in undergraduate dental basic research education (UDBRE) with the aim of nurturing the research potential of undergraduate students. Methods: We conducted a cross-sectional study among medical undergraduates enrolled at the School of Stomatology, Guangzhou Medical University. Descriptive statistics were employed to comprehensively analyze UDBRE's fundamental aspects. Kendall rank correlation analysis was performed to evaluate the relationship between the quality of feedback provided by tutors to undergraduates and the students' scientific research abilities. Additionally, multivariate logistic regression analysis was employed to uncover the factors influencing the effectiveness of UDBRE. Results: A total of 168 medical students were surveyed with a valid response rate of 93.85%. The effectiveness of UDBRE was demonstrated by undergraduates' self-rated research abilities, active participation in scientific research projects, and a certain amount of academic outputs. Significant and positive correlations (𝓣b> 0.5, p < 0.001) were identified between the tutor-undergraduate feedback quality and students' self-rated scores for scientific research abilities. These abilities included developing scientific questions, designing research projects, retrieving and reading literature, academic writing, experiment operation, and analyzing and evaluating experimental results. Positive effects on students' academic performance (p < 0.05) were observed when higher-quality feedback, an authoritative tutoring style and tutors with middle-career experience were present. Conclusion: This study underscores the pivotal role of UDBRE in fostering the scientific research aptitude of medical undergraduates. It emphasizes the constructive influence of tutor-undergraduate feedback, authoritative teaching styles, providing valuable insights for establishing an effective mentorship framework.

Research on the osteogenesis and biosafety of ECM-Loaded 3D-Printed Gel/SA/58sBG scaffolds.

Employing scaffolds containing cell-derived extracellular matrix (ECM) as an alternative strategy for the regeneration of bone defects has shown prominent advantages. Here, gelatin (Gel), sodium alginate (SA) and 58s bioactive glass (58sBG) were incorporated into deionized water to form ink, which was further fabricated into composite scaffolds by the 3D printing technique. Then, rat aortic endothelial cells (RAOECs) or rat bone mesenchymal stem cells (RBMSCs) were seeded on the scaffolds. After decellularization, two kinds of ECM-loaded scaffolds (RAOECs-ECM scaffold and RBMSCs-ECM scaffold) were obtained. The morphological characteristics of the scaffolds were assessed meticulously by scanning electron microscopy (SEM). In addition, the effects of scaffolds on the proliferation, adhesion, and osteogenic and angiogenic differentiation of RBMSCs were evaluated by Calcein AM staining and reverse transcription polymerase chain reaction (RT-PCR). In vivo, full-thickness bone defects with a diameter of 5 mm were made in the mandibles of Sprague-Dawley (SD) rats to assess the bone regeneration ability and biosafety of the scaffolds at 4, 8 and 16 weeks. The osteogenic and angiogenic potential of the scaffolds were investigated by microcomputed tomography (Micro-CT) and histological analysis. The biosafety of the scaffolds was evaluated by blood biochemical indices and histological staining of the liver, kidney and cerebrum. The results showed that the ECM-loaded scaffolds were successfully prepared, exhibiting interconnected pores and a gel-like ECM distributed on their surfaces. Consistently, in vitro experiments demonstrated that the scaffolds displayed favourable cytocompatibility. In vitro osteogenic differentiation studies showed that scaffolds coated with ECM could significantly increase the expression of osteogenic and angiogenic genes. In addition, the results from mandibular defect repair in vivo revealed that the ECM-loaded scaffolds effectively promoted the healing of bone defects when compared to the pure scaffold. Overall, these findings demonstrate that both RAOECs-ECM scaffold and RBMSCs-ECM scaffold can greatly enhance bone formation with good biocompatibility and thus have potential for clinical application in bone regeneration.

Association between chronic obstructive pulmonary disease and periodontitis: The common role of innate immune cells?

Innate immune cells are of broad interest in a variety of diseases. These cells include neutrophils, macrophages, dendritic cells and mast cells, etc. Innate immune cells are often mentioned in inflammatory diseases as the first line of defense against pathogens' invasion. As chronic obstructive pulmonary disease and periodontitis are inflammatory diseases, innate immune cells play an important role in the development of both diseases. COPD and periodontitis are common epidemic diseases with a very high prevalence, thus affecting a large number of people and also reducing the quality of life of patients. In addition, epidemiological studies suggested a link between the two, creating a co-morbid burden, but the mechanism of the link is yet to be explained. This article discusses the possible mechanism of the link between the two diseases in terms of innate immune cells and discusses possible future targeted therapies that could alleviate the burden on patients.

The role of Th17 cells: explanation of relationship between periodontitis and COPD?

Periodontitis and chronic obstructive pulmonary disease (COPD) are chronic inflammatory diseases with common risk factors, such as long-term smoking, age, and social deprivation. Many observational studies have shown that periodontitis and COPD are correlated. Moreover, they share a common pathophysiological process involving local accumulation of inflammatory cells and cytokines and damage of soft tissues. The T helper 17 (Th17) cells and the related cytokines, interleukin (IL)-17, IL-22, IL-1ß, IL-6, IL-23, and transforming growth factor (TGF)-ß, play a crucial regulatory role during the pathophysiological process. This paper reviewed the essential roles of Th17 lineage in the occurrence of periodontitis and COPD. The gaps in the study of their common pathological mechanism were also evaluated to explore future research directions. Therefore, this review can provide study direction for the association between periodontitis and COPD and new ideas for the clinical diagnosis and treatment of the two diseases.

The Role of Oral Microbiota in Chronic Obstructive Pulmonary Disease.

Studies have shown that oral microbiota dysbiosis affects patients' lung function, promoting the development and acute exacerbation of chronic obstructive pulmonary disease (COPD). In this paper, we review the mechanisms potentially linking COPD with periodontitis. Oral microbiota enters the respiratory system through clinical microaspiration to aggravate lung microbiota dysbiosis and induce lung injury by entering the respiratory tract directly. Appropriate interventions for dysbiosis such as periodontal therapy or oral microbial transplantation may prevent the progression of COPD.

Drug-loading three-dimensional scaffolds based on hydroxyapatite-sodium alginate for bone regeneration.

Bone tissue engineering is a promising approach for tackling clinical challenges. Osteoprogenitor cells, osteogenic factors, and osteoinductive/osteoconductive scaffolds are employed in bone tissue engineering. However, scaffold materials remain limited due to their source, low biocompatibility, and so on. In this study, a composite hydrogel scaffold composed of hydroxyapatite (HA) and sodium alginate (SA) was manufactured using three-dimensional printing. Naringin (NG) and calcitonin-gene-related peptide (CGRP) were used as osteogenic factors in the fabrication of drug-loaded scaffolds. Investigation using animal experiments, as well as scanning electron microscopy, cell counting kit-8 testing, alkaline phosphatase staining, and alizarin red-D staining of bone marrow mesenchymal stem cell culture showed that the three scaffolds displayed similar physicochemical properties and that the HA/SA/NG and HA/SA/CGRP scaffolds displayed better osteogenesis than that of the HA/SA scaffold. Thus, the HA/SA scaffold could be a biocompatible material with potential applications in bone regeneration. Meanwhile, NG and CGRP doping could result in better and more positive proliferation and differentiation.

Mmu_circ_003795 regulates osteoblast differentiation and mineralization in MC3T3­E1 and MDPC23 by targeting COL15A1.

Circular RNAs (circRNAs) are a class of non­coding RNAs that exhibit important regulatory roles in various biological processes. However, the role of circRNAs and their potential role in osteoblast differentiation and mineralization is unclear. The aim of the present study was to investigate the expression of mmu_circ_003795 and its effect on collagen type XV α 1 chain (COL15A1). First, it was identified that the expression levels of mmu_circ_003795 and osteopontin (OPN) were upregulated in the induced cells. Silencing of mmu_circ_003795 reduced the gene and protein levels of COL15A1 and OPN, whereas the expression level of mmu­microRNA (miR)­1249­5p was upregulated. In addition, after 7 or 14 days of induction, alkaline phosphatase and Alizarin Red­S staining were decreased in the mmu_circRNA_003795 inhibitory group compared with the negative control group. In conclusion, mmu_circ_003795 may regulate osteoblast differentiation and mineralization in MC3T3­E1 and MDPC23 cells via mmu­miR­1249­5p by targeting COL15A1.

Calcitonin gene­related peptide regulates FOSL2 expression and cell proliferation of BMSCs via mmu_circRNA_003795.

Circular RNAs (circRNAs) are a class of non­coding RNAs that may have important regulatory potency in various biological processes. However, the role of circRNAs and their potential functions in bone marrow mesenchymal stem cells of mice (BMSCs) are still ambiguous. The current study aims to examine the expression of circRNAs and to investigate their effects on FOS like 2 AP­1 transcription factor subunit (FOSL2) expression following stimulation of BMSCs with calcitonin gene­related peptide (CGRP). RNA generated from BMSCs stimulated with or without CGRP was used in a microarray to detect expression of circRNAs. There were 58 significantly differentially expressed circRNAs following CGRP treatment, with 44 circRNAs downregulated and 14 upregulated. Bioinformatics analysis and regulatory networks were used to identify the potential interactions between circRNAs and microRNAs (miRs). mmu_circRNA_003795 was significantly increased in the CGRP­stimulated BMSCs compared with the blank control. Silencing of mmu_circRNA_003795, significantly increased the expression of mmu_miR­504­3p, whereas FOSL2 expression and cell proliferation were decreased. Furthermore, silencing of mmu_mir­504­3p using an miR inhibitor led to increased FOSL2 expression. Additionally, silencing of mmu_circRNA_003795 using small interfering RNA induced marked alterations in the cell cycle of BMSCs. The results demonstrated that mmu_circRNA_003795 can indirectly regulate FOSL2 expression via sponging of miR­504­3p, resulting in alterations in BMSC proliferation.

3D printing mesoporous bioactive glass/sodium alginate/gelatin sustained release scaffolds for bone repair.

Drug delivery and release are a major challenge fabricating bone tissue engineering. In this study, we fabricated new sustained release hydrogel scaffolds composited of mesoporous bioactive glass, sodium alginate and gelatin by a three-dimensional printing technique. Naringin and calcitonin gene-related peptide were used as drugs to prepare drug-loaded scaffolds by direct printing or surface absorption. The physicochemical properties of the scaffolds and the drug release profiles of the two drug-loading models were investigated. We also examined the biocompatibility of the scaffolds, as well as the effect of the released medium on the proliferation and osteogenic differentiation of human osteoblast-like MG-63 cell. The results showed that the scaffolds had a high porosity (approximately 80%) with an interconnected cubic pore structure, rough surface morphology, bioactivity and strong biocompatibility. Furthermore, the naringin or calcitonin gene-related peptide co-printed into the scaffold displayed a steady sustained release behaviour for up to 21 days without an initial burst release, while both naringin and calcitonin gene-related peptide absorbed onto the surface of the scaffold were completely released within two days. MG-63 cells cultured with the extraction containing released drugs displayed promoted cell proliferation and the expression of osteogenesis-related genes more effectively compared with the drug-free extractions. Therefore, these results demonstrate that the developed mesoporous bioactive glass/sodium alginate/gelatin sustained release scaffolds provide a potential application for bone tissue engineering.

Mm9_circ_009056 enhances osteogenesis by targeting BMP7 via CGRP-mediated miR-22-3p.

Circular RNAs (circRNAs) are noncoding RNAs that can function as miRNA sponges, post-transcriptionally regulating the expression of genes. Here, we report a novel positive function of mm9_circ_009056 during osteogenesis in regulating bone morphogenetic protein 7 (BMP7) through miR-22-3p. First, we found that calcitonin gene-related peptide (CGRP) had great osteogenesis function on MC3T3 cells. Then aberrant expression of mm9_circ_009056 were confirmed in CGRP-induced cells. Furthermore, the expression of mm9_circ_009056 was up-regulated in the CGRP-induced cells, whereas miR-22-3p was obviously decreased. Silencing of mm9_circ_009056 increased the expression of miR-22-3p and decreased the gene and protein levels of BMP7, RUNX2. Cells proliferation and growth were also inhibited following silengcing. The protein levels of BMP7 and RUNX2 decreased after mimics transfection and increased after inhibitors transfection. In summary, mm9_circ_009056 may function as a sponge for miR-22-3p to regulate osteogenesis in CGRP-induced cells.