Search Results (427)

Sarcopenia is a progressive age-related musculoskeletal disorder characterized by loss of muscle mass, strength, and physical performance, contributing to functional decline and increased risk of disability. Emerging evidence suggests that vitamin D (Vit D) plays a pivotal role in skeletal muscle physiology beyond its classical functions in bone metabolism. This review aims to critically analyze the relationship between serum Vit D levels and sarcopenia in older adults, focusing on pathophysiological mechanisms, diagnostic criteria, clinical evidence, and preventive strategies. An integrative narrative review of observational studies, randomized controlled trials, and meta-analyses published in the last decade was conducted. The analysis incorporated international diagnostic criteria for sarcopenia (EWGSOP2, AWGS, FNIH, IWGS), current guidelines for Vit D sufficiency, and molecular mechanisms related to Vit D receptor (VDR) signaling in muscle tissue. Low serum 25-hydroxyvitamin D levels are consistently associated with decreased muscle strength, reduced physical performance, and increased prevalence of sarcopenia. Although interventional trials using Vit D supplementation report variable results, benefits are more evident in individuals with baseline deficiency and when combined with protein intake and resistance training. Mechanistically, Vit D influences muscle health via genomic and non-genomic pathways, regulating calcium homeostasis, mitochondrial function, oxidative stress, and inflammatory signaling. Vit D deficiency represents a modifiable risk factor for sarcopenia and functional impairment in older adults. While current evidence supports its role in muscular health, future high-quality trials are needed to establish optimal serum thresholds and dosing strategies for prevention and treatment. An individualized, multimodal approach involving supplementation, exercise, and nutritional optimization appears most promising. Full article

Periodontitis, a chronic inflammatory disease, causes alveolar bone loss. Current treatments show limitations in achieving dual antimicrobial and anti-inflammatory effects. We evaluated an emodin-loaded thermoresponsive hydrogel as a local drug delivery system for periodontitis treatment. Emodin itself demonstrated antibacterial activity against Porphyromonas gingivalis, with minimal inhibitory and minimal bactericidal concentrations of 50 μM. It also suppressed mRNA expression of proinflammatory cytokines [tumor necrosis factor alpha, interleukin (IL)-1β, and IL-6] in lipopolysaccharide-stimulated RAW 264.7 cells. The hydrogel, formulated with poloxamers and carboxymethylcellulose, remained in a liquid state at room temperature and formed a gel at 34 °C, providing sustained drug release for 96 h and demonstrating biocompatibility with human periodontal ligament stem cells while exhibiting antibacterial activity against P. gingivalis. In a rat model of periodontitis, the hydrogel significantly reduced alveolar bone loss and inflammatory responses, as confirmed by micro-computed tomography and reverse transcription quantitative polymerase chain reaction of gingival tissue. The dual antimicrobial and anti-inflammatory properties of emodin, combined with its thermoresponsive delivery system, provide advantages over conventional treatments by maintaining therapeutic concentrations in the periodontal pocket while minimizing systemic exposure. This shows the potential of emodin-loaded thermoresponsive hydrogels as effective local delivery systems for periodontitis treatment. Full article

Osteoclastogenesis—the activation and differentiation of osteoclasts—is one of the pivotal processes of bone remodeling and is regulated by RANKL/RANK signaling, the decoy function of osteoprotegerin (OPG), and a cascade of pro- and anti-inflammatory cytokines. The disruption of this balance leads to pathological bone loss in diseases such as osteoporosis and rheumatoid arthritis. FFAR4 (Free Fatty Acid Receptor 4), a G protein-coupled receptor for long-chain omega-3 fatty acids, has been confirmed as a key mediator of metabolic and anti-inflammatory effects. This review focuses on how FFAR4 acts as the selective receptor for the omega-3 fatty acid docosahexaenoic acid (DHA). It activates two divergent signaling pathways. The Gαq-dependent cascade facilitates intracellular calcium mobilization and ERK1/2 activation. Meanwhile, β-arrestin-2 recruitment inhibits NF-κB. These collective actions reshape the cytokine environment. In macrophages, DHA–FFAR4 signaling lowers the levels of TNF-α, interleukin-6 (IL-6), and IL-1β while increasing IL-10 secretion. Consequently, the activation of NFATc1 and NF-κB p65 is profoundly suppressed under TNF-α or RANKL stimulation. Additionally, DHA modulates the RANKL/OPG axis in osteoblastic cells by suppressing RANKL expression, thereby reducing osteoclast differentiation in an inflammatory mouse model. Full article

Three-dimensional cell culture systems are relevant in vitro models for studying cellular behavior. In this regard, this present study investigates the interaction between human osteoblast-like cells and 3D-printed scaffolds mimicking physiological and osteoporotic bone structures under simulated microgravity conditions. The objective is to assess the effects of scaffold architecture and dynamic culture conditions on cell adhesion, proliferation, and metabolic activity, with implications for osteoporosis research. Polylactic acid scaffolds with physiological (P) and osteoporotic-like (O) trabecular architectures were 3D-printed by means of fused deposition modeling technology. Morphometric characterization was performed using micro-computed tomography. Human osteoblast-like SAOS-2 and U2OS cells were cultured on the scaffolds under static and dynamic simulated microgravity conditions using a rotary cell culture system (RCCS). Scaffold biocompatibility, cell viability, adhesion, and metabolic activity were evaluated through Bromodeoxyuridine incorporation assays, a water-soluble tetrazolium salt assay, and an enzyme-linked immunosorbent assay of tumor necrosis factor-α secretion. Both scaffold models supported osteoblast-like cell adhesion and growth, with an approximately threefold increase in colonization observed on the high-porosity O scaffolds under dynamic conditions. The dynamic environment facilitated increased surface interaction, amplifying the effects of scaffold architecture on cell behavior. Overall, sustained cell growth and metabolic activity, together with the absence of detectable inflammatory responses, confirmed the biocompatibility of the system. Scaffold microstructure and dynamic culture conditions significantly influence osteoblast-like cell behavior. The combination of 3D-printed scaffolds and a RCCS bioreactor provides a promising platform for studying bone remodeling in osteoporosis and microgravity-induced bone loss. These findings may contribute to the development of advanced in vitro models for biomedical research and potential countermeasures for bone degeneration. Full article

Senescent cells secrete pro-inflammatory cytokines, collectively referred to as the senescence-associated secretory phenotype (SASP). Certain pro-inflammatory SASP factors are known to inhibit the differentiation of bone-forming osteoblast while promoting the differentiation of bone-resorbing osteoclasts, thereby causing osteoporosis. In this study, we screened cabozantinib, a tyrosine kinase inhibitor used to treat medullary thyroid cancer, for its ability to reduce doxorubicin-induced cellular senescence in both osteoblast and osteoclast progenitors. This non-cytotoxic agent suppressed the secretion of SASP factors (e.g., TNFα, IL1α, IL1β, IL6, and CCL2) from senescent osteoblast and osteoclast progenitors, resulting in enhanced osteoblast differentiation and reduced osteoclast differentiation. Furthermore, intraperitoneal administration of cabozantinib to age-related estrogen-deficient mice subjected to ovariectomy prevented bone loss without apparent side effects, increasing osteoblast numbers and reducing osteoclast numbers along the surface of the trabecular bone. In summary, our findings suggest that anti-aging cabozantinib has potential as a preventive anti-osteoporotic agent by promoting osteogenesis and inhibiting osteoclastogenesis through the repression of SASP. Full article

Periodontitis is a chronic, multifactorial inflammatory disease characterized by the progressive destruction of the periodontal supporting tissues, including alveolar bone, potentially resulting in tooth loss. Etiopathogenesis involves a dysbiotic shift in the subgingival microbiota where the presence of pathogenic species such as Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, and Treponema denticola has been documented. This disbalance is combined with an inadequate host immune response, often exacerbated by other systemic comorbidities including diabetes mellitus and cardiovascular diseases. Conventional therapy typically comprises mechanical debridement and adjunctive local or systemic antimicrobials, but emerging antibiotic resistance highlights a need for alternative adjuvant therapeutic strategies. The present descriptive analysis of microbiome and clinical trends study evaluated the adjuvant effects of a clinoptilolite-based zeolite material, namely PMA-zeolite, with professional prophylaxis on clinical and microbiological parameters in patients with chronic periodontitis over a 10-week period. Clinical assessment revealed significant reductions in bleeding on probing (BoP) and periodontal pocket depth (PD), indicating improved inflammatory status. Microbiome profiling demonstrated a marked decrease in key periodontal pathogens, suggesting that PMA-zeolite can help rebalance the oral microbiome. These findings suggest that the combined therapy exhibits promising anti-inflammatory and antimicrobial properties, indicating its role in promoting microbial homeostasis and reducing periodontal inflammation. However, further investigation through larger, controlled clinical trials is needed to validate the efficacy of the therapy. Full article

Periodontitis is a chronic inflammatory disease caused by periodontopathic bacteria such as Porphyromonas gingivalis (P. gingivalis), which leads to alveolar bone destruction and systemic inflammation. Emerging evidence suggests that probiotics may mitigate periodontal pathology. To systematically evaluate the alleviative effects and mechanisms of different forms of probiotics, including live bacteria and postbiotics, on periodontitis, we first screened and identified Ligilactobacillus salivarius CCFM1332 (L. salivarius CCFM1332) through in vitro antibacterial and anti-biofilm activity assays. Subsequently, we investigated its therapeutic potential in a rat model of experimental periodontitis. The results demonstrated that both live L. salivarius CCFM1332 (PL) and its postbiotics (PP) significantly reduced the gingival index (GI) and probing depth (PD) in rats, while suppressing oral colonization of P. gingivalis. Serum pro-inflammatory cytokine levels were differentially modulated: the PL group exhibited reductions in interleukin-17A (IL-17A), interleukin-6 (IL-6), and interleukin-1β (IL-1β) by 39.31% (p < 0.01), 17.26% (p < 0.05), and 14.74% (p < 0.05), respectively, whereas the PP group showed decreases of 34.79% (p < 0.05), 29.85% (p < 0.01), and 19.74% (p < 0.05). Micro-computed tomography (Micro-CT) analysis demonstrated that compared to the periodontitis model group (PM), the PL group significantly reduced alveolar bone loss (ABL) by 30.1% (p < 0.05) and increased bone volume fraction (BV/TV) by 49.5% (p < 0.01). In contrast, while the PP group similarly decreased ABL by 32.7% (p < 0.05), it resulted in a 40.4% improvement in BV/TV (p > 0.05). Histological assessments via hematoxylin and eosin (H&E) and tartrate-resistant acid phosphatase (TRAP) staining confirmed that both the PL group and the PP group alleviated structural damage to alveolar bone-supporting tissues and reduced osteoclast-positive cell counts. This study suggests that live L. salivarius CCFM1332 and its postbiotics reduce alveolar bone resorption and attachment loss in rats through antibacterial and anti-inflammatory pathways, thereby alleviating periodontal inflammation in rats. Full article

Osteoclasts, which are derived from myeloid precursors, are essential for physiologic bone remodeling but also mediate pathological bone loss in inflammatory diseases such as periodontitis and rheumatoid arthritis. Lysine-specific demethylase (LSD1/KDM1A) is a histone demethylase that modulates the chromatin landscape via demethylation of H3K4me1/2 and H3K9me1/2, thereby regulating the expression of genes essential for deciding cell fate. We previously demonstrated that myeloid-specific deletion of LSD1 (LSD1LysM-Cre) disrupts osteoclast differentiation, leading to enhanced BV/TV under physiological conditions. In this study, we show that LSD1LysM-Cre female mice are similarly resistant to inflammatory bone loss in both ligature-induced periodontitis and K/BxN serum-transfer arthritis models. Bulk RNA-seq of mandibular-derived preosteoclasts from LSD1LysM-Cre mice with ligature-induced periodontitis revealed the upregulation of genes involved in inflammation, lipid metabolism, and immune response. Notably, LSD1 deletion blocked osteoclastogenesis even under TGF-β and TNF co-stimulation, which is an alternative RANKL-independent differentiation pathway. Upregulation of Nlrp3, Hif1α, and Acod1 in LSD1LysM-Cre preosteoclasts suggests that LSD1 is essential for repressing inflammatory and metabolic programs that otherwise hinder osteoclast commitment. These findings establish LSD1 as a critical epigenetic gatekeeper integrating inflammatory and metabolic signals to regulate osteoclast differentiation and bone resorption. Therapeutic inhibition of LSD1 may selectively mitigate inflammatory bone loss while preserving physiological bone remodeling. Full article

Peri-implantitis is an inflammatory disease-causing bone loss around dental implants, often requiring reconstructive surgical therapies to reduce probing depth and regenerate bone. However, such surgeries are frequently complicated by postoperative issues. This retrospective case series aimed to identify the main postoperative complications following the reconstructive treatment of peri-implant bone defects in peri-implantitis patients. Data from 14 patients with 21 affected implants were analyzed, including demographics, oral hygiene, surgical techniques, and complications such as wound dehiscence, membrane exposure, and infections. Wound dehiscence was measured using Image J^® software version 1.54. Descriptive and bivariate analyses were performed. The results showed that 11 implants (52.4%; 95% confidence interval (95%CI): 29% to 76%) in nine patients (57.1%; 95%CI = 27% to 87%) developed soft tissue dehiscence after one week, with membrane exposure observed in 4 implants. Dehiscence was significantly associated with mandibular implant location (p = 0.003), poor interproximal hygiene (p = 0.008), and membrane exposure (p = 0.034). No postoperative infections were recorded. In conclusion, more than half of peri-implantitis patients undergoing reconstructive surgery experience wound dehiscence, particularly in cases involving mandible, poor hygiene, and membrane exposure. This complication might compromise bone regeneration and reduce the treatment success rate. These results should be interpreted cautiously due to study design limitations (retrospective design, lack of a control group, and small sample size). Full article

Diabetes is a risk factor for periodontitis. Increasing evidence suggests that a central player in this link is the vacuolar H+-ATPase (V-ATPase), which provides a physical and functional core for regulation by the catabolic lysosomal AMP-activated protein kinase complex (L-AMPK) and the anabolic mammalian target of rapamycin complex 1 (mTORC1). These complexes detect levels of various cellular nutrients, including glucose at the lysosome, and promote cellular responses to restore homeostasis. The high-glucose conditions of diabetes foster anabolic mTORC1 signaling that increases inflammation and inflammatory bone resorption in response to periodontal infections. Here, we review the structure and composition of V-ATPase, L-AMPK, mTORC1, and other elements of the energy-sensing platform. Mechanisms by which V-ATPase passes signals to the complexes are examined and recent data are reviewed. Current anti-bone resorptive therapeutics, bisphosphonates and denosumab, enhance the risk of medicine-related osteonecrosis of the jaw (MRONJ) and are not used to treat periodontal bone loss. Accumulating data suggest that it may be possible to target inflammatory bone resorption through agents that stimulate L-AMPK, including metformin and glucagon-like peptide-1 agonists. This approach may reduce inflammatory bone resorption without major effects on overall bone remodeling or increased risk of MRONJ. Full article

Background: Periodontitis is a chronic inflammatory disease influenced by host aging, yet the specific effects of aging on disease susceptibility remain unclear. Objective: This study aimed to evaluate whether aging increases susceptibility to Porphyromonas gingivalis (P. gingivalis)-induced periodontitis in a murine model. We formulated the null hypothesis that age does not affect susceptibility to periodontal bone loss. Methods: Young (8 weeks) and aged (78 weeks) male C57BL/6 mice were randomly assigned into four groups: young control, young infected, old control, and old infected (n = 8 per group, except for old control, where n = 7). Experimental periodontitis was induced by oral application of P. gingivalis suspended in 5% carboxymethylcellulose (CMC), administered every other day, for a total of three applications. Alveolar bone loss was assessed 39 days after the last inoculation using histomorphometric measurement of buccal distance from the cemento-enamel junction to the alveolar bone crest (CEJ–ABC distance) and micro-computed tomography (μCT) at mesial and distal interdental sites. Bonferroni’s correction was applied to the Mann–Whitney U Test to determine statistical significance. A p-value of less than 0.05 was considered statistically significant. Results: Morphometric analysis showed significantly greater buccal bone loss in infected mice versus controls in both age groups (young: 0.193 mm vs. 0.100 mm, p < 0.01; old: 0.262 mm vs. 0.181 mm, p < 0.01). μCT analysis revealed that interdental bone loss was significant only in aged infected mice (mesial: 0.155 mm vs. 0.120 mm, p < 0.05; distal: 0.185 mm vs. 0.100 mm, p < 0.01), and not significant in young infected mice. Conclusions: Aging significantly exacerbates P. gingivalis-induced alveolar bone loss, particularly in interdental regions. These results allowed us to reject the null hypothesis. This study validates a clinically relevant murine model for analyzing age-related periodontitis and provides a foundation for investigating underlying molecular mechanisms and potential therapeutic interventions. Full article

Proanthocyanidins (PACs), also called condensed tannins, are oligomers or polymers composed of flavan-3-ols. This review aimed to explore the potential role of PACs in ameliorating oral health problems, with a particular focus on their effects within the intestine—especially the colon, where most orally ingested PACs are believed to accumulate. Previous studies suggest that PACs can be beneficial in periodontal disease as well as in the osseointegration of dental implants in patients with osteoporosis. Periodontal disease is worsened by lipopolysaccharides (LPS) that enter the bloodstream due to disrupted tight junctions of intestinal epithelial cells, along with inflammatory cytokines released by activated macrophages. A similar mechanism is thought to affect osseointegration: LPS-induced inflammatory cytokines originating in the intestine can enter the bloodstream, contributing to bone loss and impaired integration of dental implants. PACs absorbed by intestinal epithelial cells can function as prooxidants, triggering the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which strengthens the gut barrier. This enhanced barrier reduces the levels of LPS and inflammatory cytokines in the blood, leading to the alleviation of periodontal inflammation and increased alveolar bone density, thereby promoting better osseointegration of dental implants. Full article

Periodontitis is an inflammatory disease that affects the periodontal supporting tissues. Its cardinal clinical manifestations encompass gingival inflammation, periodontal pocket formation, and alveolar bone resorption. Urolithin A (UA), a gut microbiota-derived metabolite of ellagitannins, is known for its anti-inflammatory and osseous-protective properties. Nonetheless, the impact of UA on periodontitis remains unknown. To investigate the preventive effect of UA, we employed a lipopolysaccharide (LPS)-induced inflammation model in RAW 264.7 mouse macrophages, a receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation model, and a ligature-induced periodontitis model in mice. The expression of inflammatory factors (tumor necrosis factor-α, TNF-α; interleukin-6, IL-6) was analyzed to assess anti-inflammatory efficacy. Bone loss in mice with periodontitis was assessed through histological and imaging techniques, including haematoxylin and eosin staining to evaluate alveolar bone morphology, Masson’s trichrome staining to visualize collagen fiber distribution, and micro-computed tomography scanning to quantify bone structural parameters. Additionally, we investigated the underlying mechanisms by examining osteoclast activity through tartrate-resistant acid phosphatase staining and the expression levels of proteins RANKL and osteoprotegerin (OPG). We found that UA reduced IL-6 and TNF-α levels in vitro and in vivo, inhibited osteoclast differentiation, and decreased the RANKL/OPG ratio in periodontitis mice. Full article

Periodontitis is a highly prevalent, irreversible inflammatory disease characterized by the destruction of tooth-supporting tissues, eventually leading to tooth loss. Conventional treatment involves the mechanical removal of the subgingival biofilm, which is a major cause of gingival inflammation. However, the inaccessibility of deep-seated polymicrobial biofilms limits its effectiveness. Despite the adjunct use of systemic antimicrobials, their low site-specific bioavailability and systemic side effects remain concerns. Local drug administration offers a targeted alternative. However, the dynamic oral environment, which is characterized by continuous salivary and gingival crevicular fluid flow, poses challenges in maintaining therapeutic drug levels. Drug delivery systems (DDSs) provide technical solutions to overcome these limitations. With advancements in materials science and nanotechnology, diverse local DDS (LDDS) formulations tailored for periodontal applications have been developed. While traditionally focused on infection control, the application of LDDSs has expanded beyond antimicrobial therapy. Increasing attention has been paid to LDDS-based regenerative strategies, which aim to overcome the limitations of conventional regenerative therapies. This review aims to provide a comprehensive overview of the current and emerging DDS strategies in periodontal therapy, focusing on their applications in infection management and bone regeneration and discussing their limitations and prospects for clinical translation. Full article

This study aimed to develop and validate a dual murine model integrating a high-fat diet (HFD) and a single streptozotocin (STZ) dose to induce diabetes mellitus (DM), alongside periodontitis (Perio) induced by ligature placement and oral inoculation with Porphyromonas gingivalis (P. gingivalis). The goal was to mimic human pathological conditions, creating a physiologically relevant environment to study the interplay between DM and Perio. A total of 128 six-week-old male C57BL/6J mice were randomly divided into four groups: Control, DM, Perio, and DM-P. DM was induced by HFD and STZ injection, and Perio by ligature placement and P. gingivalis infection. Evaluations occurred at baseline and days 7, 14, and 21. Alveolar bone loss was assessed by micro-computed tomography, and inflammation was examined histologically. DM mice showed elevated glucose levels and insulin resistance. Perio and DM-P groups experienced significant bone loss compared with Control and DM groups. The morphometric analysis revealed abundant inflammatory cells and reduced collagen fibers in Perio and DM-P groups, especially at day 7. This dual murine model successfully replicated the key features of DM and Perio, maintaining overall health of the animals, and good tolerability by those subjects to the stress of both interventional procedures. Full article