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.

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.

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.

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.