Search Results (130)

Glucose-dependent insulinotropic polypeptide (GIP) was the first incretin hormone identified, best known for promoting glucose-stimulated insulin secretion. Increasing evidence has expanded its physiological relevance beyond glucose metabolism, revealing a significant role for GIP in the gut–bone axis. In vitro studies demonstrate that GIP inhibits osteoclast differentiation and activity while promoting osteoblastic bone formation. Findings from genetic animal models and human variant analyses further support the essential role of endogenous GIP signaling in maintaining bone mass and quality. Exogenous administration of GIP suppresses the bone-resorption marker C-terminal telopeptide of type I collagen (CTX) and increases the bone-formation marker procollagen type I N-terminal propeptide (P1NP) in healthy individuals, reflecting an acute shift toward reduced bone resorption and enhanced bone formation. Moreover, GIP confers protection against bone deterioration in multiple pathological conditions, including postmenopausal osteoporosis, inflammatory bone loss, obesity, and diabetes, etc., suggesting therapeutic potential beyond physiological contexts. Recent evidence also shows that GIP attenuates orthodontic tooth movement by limiting mechanically induced osteoclast activity, highlighting its broader skeletal actions. In this review, we summarize recent advances regarding the role of GIP in bone metabolism, integrating evidence from cellular studies, animal models and human investigations, and discuss future directions for GIP-based interventions. Full article

With the intensification of global population aging, the co-morbidity rate of periodontitis and osteoporosis has significantly increased. The two are pathologically intertwined, forming a vicious cycle characterized by bone immunoregulatory dysfunction in the periodontal microenvironment, abnormal accumulation of reactive oxygen species (ROS), and disruption of bone homeostasis. Conventional mechanical debridement and anti-infective therapy can reduce the pathogen load, but in some patients, it remains challenging to achieve long-term stable control of inflammation and bone resorption. Furthermore, abnormal bone metabolism in the context of osteoporosis further weakens the osteogenic response during the repair phase, limiting the efficacy of these treatments. Bioinspired cell membrane-coated nanoparticles (CMNPs) have emerged as an innovative technological platform. By mimicking the biointerface properties of source cells—such as red blood cells, platelets, white blood cells, stem cells, and their exosomes—CMNPs enable targeted drug delivery, prolonged circulation within the body, and intelligent responses to pathological microenvironments. This review systematically explores how biomimetic design leverages the advantages of natural biological membranes to address challenges in therapeutic site enrichment and tissue penetration, in vivo circulation stability and effective exposure maintenance, and oxidative stress and immune microenvironment intervention, as well as functional regeneration supported by osteogenesis and angiogenesis. Additionally, we conducted an in-depth analysis of the key challenges encountered in translating preclinical research findings into clinical applications within this field, including issues such as the feasibility of large-scale production, batch-to-batch consistency, and long-term biosafety. This review lays a solid theoretical foundation for advancing the clinical translation of synergistic treatment strategies for periodontitis with osteoporosis and provides a clear research and development pathway. Full article

Background: X-linked hypophosphatemic rickets (XLH) is a rare hereditary disorder characterized by renal phosphate wasting and impaired bone mineralization. Oral manifestations such as spontaneous periapical lesions and dental abscesses in the absence of caries or trauma may precede systemic features in XLH due to underlying dentin hypomineralization and enamel–dentin junction defects, and could serve as early diagnostic indicators. Case Report: We report on the case of a 4-year-old boy referred to our pediatric dental unit with recurrent intraoral fistulas persisting over the past year. Clinical examinations and an orthopantomogram revealed extensive root resorption and periapical pathology affecting multiple primary molars without evident caries or trauma. Laboratory investigations showed hypophosphatemia, elevated renal phosphate loss, and raised inflammatory markers (CRP (C-reactive protein) and granulocytes). Genetic testing of the child and his mother confirmed a diagnosis of X-linked hypophosphatemic rickets. Management: Due to behavioral challenges, treatment proceeded with difficulty over multiple visits. Endodontic treatment was initiated using a formalin–resorcinol technique; however, several primary molars developed progressive necrosis and required extraction. Orthodontic space maintainers were placed to preserve arch integrity and support future eruption. The patient remains under follow-up and is currently awaiting Burosumab therapy. Despite systemic management, spontaneous necroses of the primary molars persist, highlighting the refractory nature of dental involvement in XLH. Conclusions: This case underscores the pivotal role of pediatric dentists in recognizing systemic diseases through oral findings and demonstrates the challenges of managing XLH-related dental pathology, even under targeted systemic therapy. Early interdisciplinary collaboration is essential to optimize both dental and systemic outcomes in affected children. Full article

Alzheimer’s disease (AD) and osteoporosis frequently co-occur in the elderly; however, the pathophysiological link between these two diseases remains unclear. This study investigates skeletal alterations in a triple transgenic 3xTg-AD mouse model of AD (3xTg-AD), which harbors mutations in β-amyloid precursor protein (βAPP_Swe), presenilin-1 (PS1_M146V), and tau_P301L, and recapitulates key aspects of AD pathology, including age-dependent β-amyloid plaque accumulation and cognitive decline. To assess early skeletal changes, we analyzed femurs and tibiae of 2-month-old male non-Tg and 3xTg-AD mice (n = 9/group) using micro-CT. Despite the absence of β-amyloid plaques at this stage, 3xTg-AD mice showed significant cortical bone loss, with reduced bone surface, periosteal and endosteal perimeters, total and cortical cross-sectional area, and polar moment of inertia. The 3-point-bending test confirmed compromised mechanical properties, including reduced maximum load-to-fracture and stiffness. Histological analyses highlighted an increased number of Empty Osteocyte Lacunae, reduced TRAP⁺ osteocytes, and an elevated number of osteoclasts; such evidence indicates impaired osteocyte function and increased bone resorption. These findings indicate that cortical bone loss and compromised mechanical properties occur before detectable neuropathological hallmarks in this AD model. Full article

Brown tumors (BTs) are rare osteolytic lesions that typically occur in association with primary or secondary hyperparathyroidism (PHP and SHP). Excessive secretion of parathyroid hormone induces increased bone resorption, resulting in lesions characterized by fibrosis, vascularization, and hemosiderin deposition. The most common sites include the jaws, ribs, pelvis, and long bones. Clinical manifestations may involve pain, swelling, or pathological fractures. We present the case of a mandibular BT in a 48-year-old female with chronic renal failure and secondary hyperparathyroidism. The patient exhibited progressive mandibular swelling with radiological features resembling an aggressive odontogenic or malignant lesion. Laboratory analysis confirmed markedly elevated parathyroid hormone levels, while scintigraphy demonstrated increased focal uptake in the mandible and ribs. Histopathological evaluation revealed multinucleated giant cells within a fibrous stroma, consistent with BT. Despite initiation of systemic endocrine therapy, the lesion continued to enlarge, necessitating complete surgical excision of the mandibular mass. This case underscores the diagnostic dilemmas of mandibular BT, which may closely mimic aggressive jaw pathologies. Importantly, while many BTs regress after systemic management of hyperparathyroidism, this case illustrates that surgical excision may be unavoidable in patients with unstable systemic status or progressive local disease. Comprehensive clinical, radiological, laboratory, and histopathological evaluation remains essential to ensure timely diagnosis and appropriate treatment. Full article

Background: Jawbone invasion is a common and prognostically unfavorable feature of oral squamous cell carcinoma (OSCC). Although cancer-associated fibroblasts (CAFs) are recognized for their role in tumor progression, their spatial dynamics at the tumor–bone interface remain poorly understood. Methods: We analyzed 14 OSCC specimens with confirmed jawbone invasion using histopathological and immunohistochemical techniques. Digital pathology combined with AI-assisted image analysis was employed to quantify and visualize the spatial distribution of OSCC cells (RANKL-positive), CAFs (α-SMA and FAP-positive), and osteoclasts (cathepsin K-positive) within defined regions of interest at the tumor–bone invasive front. Results: A consistent laminar stromal region enriched in CAFs was observed between the tumor nests and jawbone. CAFs were spatially clustered near OSCC cells and osteoclasts, with 81% and 74% residing within 50 μm, respectively. On average, 11.4 CAFs were present per OSCC cell and 23.2 per osteoclast. These spatial proximities were largely preserved irrespective of stromal thickness, suggesting active bidirectional cellular interactions. Conclusions: Our findings demonstrate that CAFs are strategically positioned to facilitate intercellular signaling between tumor cells and osteoclasts, potentially coordinating OSCC proliferation and bone resorption. This study highlights the utility of AI-assisted spatial histology in unraveling tumor microenvironmental dynamics and proposes CAFs as potential therapeutic targets in OSCC-induced osteolytic invasion. Full article

Background: The epiphyseal vascularization of long bones generates a particular flow pattern that is important for adequate angiogenesis to be achieved. Imaging reveals that vessel development in murine long bone involves the expansion and anastomotic fusion of endothelial buds. Impaired blood flow leads to defective angiogenesis and osteogenesis and downregulation of Notch signaling in endothelial cells. We examined whether altered blood flow and endothelial signaling via the Notch pathway—a highly conserved cell–cell communication mechanism that regulates angiogenesis and vascular remodeling—contributes to hip joint degeneration. Material and Methods: In our study, we used two groups of patients. The first is a control group of 15 patients without degenerative joint pathology. The second group consists of 51 patients diagnosed with an advanced form of degenerative joint pathology. On both study groups, we used immunohistochemical markers that highlight the endothelium of epiphyseal capillaries, the collagen matrix, and the presence of joint lubricant-secreting cells. Ultrastructural analysis was performed on hematoxylin-eosin slides that were exposed to a surface electron microscope, following a previously tested protocol. Results: The results of our study show that there are numerous anastomoses between epiphyseal vessels and that these capillaries persist even after pathological bone resorption, for a certain period of time. Discussions: Our results are complementary to recent studies on this research topic that emphasize the possibility that the main cause of joint degeneration is vascular. Revascularization of an area of bone demineralization after bone infarction has become a reality. Conclusions: This study opens new perspectives regarding the research on epiphyseal capillary vascularization and the modern concept of morpho functional rehabilitation of the hip joint. Full article

The jaw bones can manifest various cysts and tumors of different origins and etiologies. Any bone lesions lacking any potential odontogenic origin might require more accurate diagnostics, adequate investigation, and careful patient anamnesis. In cases of sharply demarcated radiolucency or mixed radiolucent–radiopaque radiological appearance lesions, they can sometimes extend between the displaced tooth roots or cause their resorption. The scope of cortical bone in radiographic studies might have a different status, and lesions can spread outside of the bone. If no odontogenic feature is present, an additional blood examination for bone markers and calcium–phosphate markers is useful to establish any endocrine-related pathologies. In the primary hyperparathyroidism (PHP), bone blood markers and bone scintigraphy are very useful to establish the possible occurrence of brown tumor. On the other hand, in central giant cell granuloma (CGCG), only a direct tumor lesion biopsy might confirm the diagnosis, where in microscopic evaluation, mostly fibroblasts and secondary cells have multinucleated giant cells along with some accessory cells like macrophages, dendrocytes, and other endothelial cells. Because both lesions can have similar clinical and radiological appearances and unclear borders, with different shapes, sizes, and symptoms, it is quite important to compare both clinical and radiological patient characteristics. The authors aim to present how radiological studies alone can easily lead to lesion misdiagnosis. They also aim to emphasize how local treatment methods without advanced microsurgical reconstruction can, in some cases, improve patient outcomes. 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

Chrysanthemum species represent an economically important group of flowering plants. Many species also present a medicinal interest, notably for the treatment of inflammatory pathologies. This is the case for Chrysanthemum boreale Makino, endemic to Japan and widespread in Eastern Asia. This perennial plant has long been used in folk medicine to treat inflammatory diseases and bacterial infections. An extensive review of the scientific literature pertaining to C. boreale has been performed to analyze the origin of the plant, its genetic traits, the traditional usages, and the properties of aqueous or organic plant extracts and essential oils derived from this species. Aqueous extracts and the associated flavonoids, such as acacetin and glycoside derivatives, display potent antioxidant activities. These aqueous extracts and floral waters are used mainly as cytoprotective agents. Organic extracts, in particular those made from methanol or ethanol, essentially display antioxidant and anti-inflammatory properties useful to protect organs from oxidative damage. They can be used for neuroprotection. Essential oils from C. boreale have been used as cytoprotective or antibacterial agents. The main bioactive natural products isolated from the plant include flavonoids such as acacetin and related glycosides (notably linarin), and diverse sesquiterpene lactones (SLs). Among monomeric SLs, cumambrins and borenolide are the main products of interest, with cumambrin A targeting covalently the transcription factor NF-κB to regulate proinflammatory gene expression to limit osteoclastic bone resorption. The dimeric SL handelin, which is characteristic of C. boreale, exhibits a prominent anti-inflammatory action, with a capacity to target key proteins like kinase TAK1 and chaperone Hsp70. A few other natural products isolated from the plant (tulipinolide, polyacetylenic derivatives) are discussed. Altogether, the review explores all medicinal usages of the plant and the associated phytochemical panorama, with the objective of promoting further botanical and chemical studies of this ancestral medicinal species. Full article

Osteoporosis is a systemic bone disorder characterized by decreased bone mass and deteriorated microarchitecture, leading to an increased risk of fractures. Recent studies have revealed that its pathogenesis involves complex biological processes beyond bone remodeling, including oxidative stress, chronic inflammation, cellular senescence, osteoimmunology, gut microbiota alterations, and epigenetic modifications. Oxidative stress disrupts bone homeostasis by promoting excessive free radical production and osteoclast activity. Chronic inflammation and the accumulation of senescent cells impair skeletal repair mechanisms. Advances in osteoimmunology have highlighted the critical role of immune–bone crosstalk in regulating bone resorption and formation. Moreover, the gut–bone axis, mediated by microbial metabolites, influences bone metabolism through immune and endocrine pathways. Epigenetic changes, such as DNA methylation and histone modification, contribute to gene–environment interactions, affecting disease progression. Multi-omics approaches (genomics, proteomics, and metabolomics) systematically identify molecular networks and comorbid links with diabetes/cardiovascular diseases, revealing pathological feedback loops that exacerbate bone loss. In conclusion, osteoporosis pathogenesis extends beyond bone remodeling to encompass systemic inflammation, immunometabolic dysregulation, and gut microbiota–host interactions. Future research should focus on integrating multi-omics biomarkers with targeted therapies to advance precision medicine strategies for osteoporosis prevention and treatment. Full article

Cathepsins are protease enzymes vital for normal physiological functions, such as digestion, coagulation, hormone secretion, bone resorption, apoptosis, autophagy, and both innate and adaptive immunity. Their altered expression and/or activity is associated with various pathological conditions, including inflammatory processes. In this study, we investigated the expression levels of cathepsins in muscle specimens collected from dogs affected by inflammatory myopathy (IM) of variable severity established through histopathological analysis. Samples collected from dogs affected by IM at mild, moderate, and severe stages and from healthy (control) dogs were analyzed for the expression profile of 35 proteases using a proteome profiler array. Among the other proteases, cathepsin B was upregulated to an extent depending on disease progression. By exploring the molecular mechanisms underlying the impact of cathepsin B on the disease, we found that the upregulation of cathepsin B in diseased tissues correlates with increased TGFβ-1 expression levels and elevated phosphorylation levels of the TGFβ-1 signaling mediator SMAD2/3. These results suggest that cathepsin B might be involved in the onset and progression of fibrosis commonly occurring in IM diseased dogs. Overall, our findings reveal that modulating cathepsin B activity may hold therapeutic potential for IM. Full article

Background/Objectives: Periodontitis and diabetes mellitus share a well-established bidirectional relationship, where hyperglycemia exacerbates periodontal inflammation, and periodontal disease further impairs glycemic control. Within the diabetic periodontal microenvironment, an imbalance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages promotes chronic inflammation, oxidative stress, delayed healing, and alveolar bone resorption. Resveratrol (RSV), a polyphenol with antioxidant, anti-inflammatory, and pro-osteogenic properties, holds potential to restore macrophage balance. However, its clinical application is limited by poor bioavailability and instability. This study aimed to develop and evaluate a novel RSV delivery system to overcome these limitations and promote periodontal tissue regeneration under diabetic conditions. Methods: A drug delivery system comprising RSV-loaded solid lipid nanoparticles embedded within a cross-linked hyaluronic acid hydrogel (RSV@CLgel) was formulated. The system was tested under hyperglycemic and inflammatory conditions for its effects on macrophage polarization, cytokine expression, oxidative stress, mitochondrial function, and osteoblast differentiation. Results: RSV@CLgel effectively suppressed pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) while upregulating anti-inflammatory markers (IL-10, TGF-β). It significantly reduced oxidative stress by decreasing ROS and lipid peroxidation levels and improved mitochondrial function and antioxidant enzyme activity. Furthermore, RSV@CLgel enhanced osteoblast differentiation, as evidenced by increased ALP activity, calcium nodule formation, and upregulation of osteogenic genes (COL-I, RUNX2, OCN, OPN). It also inhibited RANKL-induced osteoclastogenesis, contributing to alveolar bone preservation. Conclusions: The RSV@CLgel delivery system presents a promising multifunctional strategy for the management of diabetic periodontitis. By modulating immune responses, reducing oxidative stress, and promoting periodontal tissue regeneration, RSV@CLgel addresses key pathological aspects of diabetes-associated periodontal disease. Full article

Bone is a highly mechanosensitive tissue, where mechanical signaling plays a central role in maintaining skeletal homeostasis. Mechanotransduction regulates the balance between bone formation and resorption through coordinated interactions among bone cells. Key mechanosensing structures—including the extracellular/pericellular matrix (ECM/PCM), integrins, ion channels, connexins, and primary cilia, translate mechanical cues into biochemical signals that drive bone adaptation. Disruptions in mechanotransduction are increasingly recognized as an important factor in osteoporosis. Under pathological conditions, impaired mechanical signaling reduces bone formation and accelerates bone resorption, leading to skeletal fragility. Defects in mechanotransduction disrupt key pathways involved in bone metabolism, further exacerbating bone loss. Therefore, targeting mechanotransduction presents a promising pharmacological strategy for osteoporosis treatment. Recent advances have focused on developing drugs that enhance bone mechanosensitivity by modulating key mechanotransduction pathways, including integrins, ion channels, connexins, and Wnt signaling. A deeper understanding of mechanosignaling mechanisms may pave the way for novel therapeutic approaches aimed at restoring bone mass, mechanical integrity, and mechanosensitive bone adaptation. Full article