Eldecalcitol alleviates diabetic periodontitis by regulating macrophage efferocytosis and polarization via SOCE machinery.

Diabetes exacerbates the occurrence and severity of periodontitis, the pathogenesis of diabetic periodontitis (DPD) is influenced by the delayed resolution of inflammation. Eldecalcitol (ED-71) has shown promise in preventing bone loss in DPD. We herein aimed to investigate the role of ED-71 in the inflammatory regression phase of DPD and elucidate the underlying mechanisms.

Simvastatin inhibits proliferation and promotes apoptosis of oral squamous cell carcinoma through KLF2 signal.

Objectives: This study aimed to explore the role and specific mechanism of the cholesterol-lowering drug simvastatin in inhibiting oral squamous cell carcinoma (OSCC).

Methods: The proliferation, apoptosis, and migration levels of OSCC cells were detected by CCK8, quantitative real-time polymerase chain reaction, Western blot, colony formation, TdT-mediated dUTP Nick-End Labeling assay, and wound healing assay. The inhibitory effect of simvastatin in vivo was detected by a mouse xenograft tumor model.

Sex difference in the morbidity and pain response with stage 0 of medication-related osteonecrosis of the jaws.

Objective: Medication-related osteonecrosis of the jaws (MRONJ) is a potentially severe complication associated with antiresorptive or antiangiogenic therapies. Prior studies, including our own clinical data, have indicated a higher incidence of MRONJ among women compare to men. However, robust evidence establishing a relationship between sex and the prevalence of MRONJ is lacking.

Menaquinone-4 prevents medication-related osteonecrosis of the jaw through the SIRT1 signaling-mediated inhibition of cellular metabolic stresses-induced osteoblast apoptosis.

Long-term usage of bisphosphonates, especially zoledronic acid (ZA), induces osteogenesis disorders and medication-related osteonecrosis of the jaw (MRONJ) in patients, thereby contributing to the destruction of bone remodeling and the continuous progression of osteonecrosis. Menaquinone-4 (MK-4), a specific vitamin K isoform converted by the mevalonate (MVA) pathway in vivo, exerts the promotion of bone formation, whereas ZA administration suppresses this pathway and results in endogenous MK-4 deficiency. However, no study has evaluated whether exogenous MK-4 supplementation can prevent ZA-induced MRONJ.

Brain-derived neurotrophic factor promotes orthodontic tooth movement by alleviating periodontal ligament stem cell senescence.

Orthodontic treatment in older adults is more difficult than in younger adults, partially due to delayed osteogenesis caused by senescence of human periodontal ligament stem cells (hPDLSCs). The production of brain-derived neurotrophic factor (BDNF) which regulates the differentiation and survival of stem cells decreases with age. We aimed to investigate the relationship between BDNF and hPDLSC senescence and its effects on orthodontic tooth movement (OTM).

Notum leads to potential pro-survival of OSCC through crosstalk between Shh and Wnt/β-catenin signaling via p-GSK3β.

Notum, which belongs to the α/β hydrolase family, is a deacylated extracellular protein that regulates the Wnt signaling pathway. Studies have found that Notum participates in the progression of colorectal cancer and hepatocellular carcinoma, but its role in oral squamous cell carcinoma (OSCC) is currently unclear. This study aimed to explore the role of Notum in regulating OSCC and further reveal the underlying mechanisms.

The mechanism underlying the TC-G 1008 rescue of reactive oxygen species (ROS)-induced osteoblast apoptosis by the upregulation of peroxiredoxin 1.

Osteoporosis is a common bone disease in the elderly with high morbidity and mortality. Previous studies have shown ROS-revulsive osteoblast apoptosis to be involved in the pathogenesis of osteoporosis. At present, a research hotspot exists on the topic of the ROS-targeted clinical treatment of osteoporosis.

ED-71 inhibited osteoclastogenesis by enhancing EphrinB2-EphB4 signaling between osteoclasts and osteoblasts in osteoporosis.

Background: Osteoporosis is a degenerative skeletal disease essentially caused by bone remodeling disorder. EphrinB2-EphB4 signaling play critical regulatory roles in bone remodeling via communication between osteoclasts and osteoblasts. Eldecalcitol (ED-71), a new vitamin D analog, is a high-potential drug for treating osteoporosis; however, its mechanism has yet to be determined.

The polypeptide OP3-4 induced osteogenic differentiation of bone marrow mesenchymal stem cells via protein kinase B/glycogen synthase kinase 3β/β-catenin pathway and promoted mandibular defect bone regeneration.

Objectives: The aims of this study were to explore: (ⅰ) the effect of the polypeptide OP 3-4 on bone regeneration in vivo; (ⅱ) the effect of OP 3-4 on osteogenic differentiation of bone marrow mesenchymal stem cells in vitro; and (ⅲ) the potential mechanism of OP 3-4 in promoting osteogenic differentiation of bone marrow mesenchymal stem cells.

Designs: 30 Wistar rats (8-week, male) were randomly divided into Control group (n = 5), Hydrogel group (n = 5), and Hydrogel loaded OP 3-4 group (n = 5). Hematoxylin and eosin staining was used to evaluate the level of bone regeneration in mandibular defect.

Notum suppresses the osteogenic differentiation of periodontal ligament stem cells through the Wnt/Beta catenin signaling pathway.

Objectives: The aims of this study were to explore: (ⅰ) the effect of Notum on periodontitis in vivo; (ⅱ) the effect of Notum on the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) in vitro; and (ⅲ) the potential mechanism of Notum in inhibiting the osteogenic differentiation of hPDLSCs.

Design: C57BL/6J mice were randomly assigned into two groups: control group (n = 4) and periodontitis group (n = 4). Immunohistochemical staining was used to evaluate the expression of Notum.

Eldecalcitol induces apoptosis and autophagy in human osteosarcoma MG-63 cells by accumulating ROS to suppress the PI3K/Akt/mTOR signaling pathway.

Eldecalcitol (ED-71) is a new type of vitamin D analog, and vitamin D has been reported to have therapeutic effects in infectious disease, autoimmune disease, and cancer. However, the anti-cancer effect of ED-71 remains unclear. The objective of this study was to explore the anti-cancer effect of ED-71 in human osteosarcoma cells and to identify the related mechanism.

Silencing FOXO1 attenuates dexamethasone-induced apoptosis in osteoblastic MC3T3-E1 cells.

Dexamethasone (DEX), a widely used glucocorticoid with strong anti-inflammatory and immunosuppressive activities, has been reported to induce apoptosis in osteoblasts, but the underlying mechanisms are still not comprehensively investigated. FOXO1 plays an important role in the regulation of cell proliferation and apoptosis. Our study aims to explore the role of FOXO1 in DEX-induced apoptosis of osteoblastic MC3T3-E1 cells through bioinformatics and experiments.

RANKL-independent modulation of osteoclastogenesis.

Osteoclasts are functional cells required for bone resorption. They are derived from hematopoietic precursors and undergo a series of differentiation and fusion steps in response to various humoral factors. Depending on the importance in osteoclastogenesis, the pathways for the differentiation of hematopoietic precursors to mature osteoclasts can be divided into two categories: canonical and the non-canonical.

Fusion and hemagglutinin proteins of canine distemper virus promote osteoclast formation through NF-κB dependent and independent mechanisms.

Paget's disease (PD) features abnormal osteoclasts (OC) which sharply increase in number and size and then intensely induce bone resorption. The purpose of this study was to determine the direct effects of canine distemper virus (CDV) and its fusion protein and hemagglutinin protein (F + H) on receptor activator of nuclear factor kappa-B ligand (RANKL) induced OC formation in vitro. Immunofluorescence assay, OC morphological and functional detection, intracellular signaling pathway detection, Real-time PCR analysis and ELISA were applied in this study.

Phenobarbital inhibits osteoclast differentiation and function through NF-κB and MAPKs signaling pathway.

The purpose of this study was to determine the direct effects of phenobarbital (PB) on receptor activator of nuclear factor kappa-B ligand (RANKL) induced osteoclast differentiation and function in vitro and in vivo. Here, PB significantly inhibited osteoclast formation and bone resorption ability induced by RANKL in vitro. Meanwhile, intracellular signaling transduction analysis revealed PB specifically decreasing the phosphorylation level of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK), respectively.

Synthesis of 1α,25-dihydroxyvitamin D analogues with α,α-difluorocycloketone at the CD-ring side chains and their biological properties in ovariectomized rats.

Two novel 1α,25-dihydroxyvitamin D derivatives containing a α,α-difluorocyclopentanone (3) or α,α-difluorocyclohexanone (4) moiety at the CD-ring side chains were designed, synthesized, and evaluated for their biological properties on restoring bone mass in ovariectomized (OVX) rats with established osteopenia. The synthesis of compounds 3 and 4 utilized the Wittig-Horner coupling to build up the vitamin D conjugated triene system, followed by the introduction of the cycloketone fragments at the side chain, and subsequent α,α-difluorination of the ketone by the treatment of the derived silyl enol ether with Selectfluor, as the key synthetic steps. In comparison with the natural 1α,25-dihydroxyvitamin D (calcitriol; 200 ng/kg/day), oral administration of compounds 3 and 4 at the dose of 25 ng/kg/day for 6 weeks led to much improved bone mass and bone density related parameters, while maintaining normal serum calcium and serum phosphorus levels.

Altered distribution of Ghrelin protein in mice molar development.

Objective: Ghrelin, an appetite-stimulating hormone, plays diverse regulatory functions in cell growth, proliferation, differentiation and apoptosis during mammalian development. There is limited information currently available regarding Ghrelin expression during mammalian tooth development, thus we aimed to establish the spatiotemporal expression of Ghrelin during murine molar odontogenesis.

Design: Immunohistochemistry was performed to detect the expression pattern of Ghrelin in mandible molar from E15.

Histochemical examination of adipose derived stem cells combined with β-TCP for bone defects restoration under systemic administration of 1α,25(OH)2D3.

The purpose of this study was to evaluate the effects of osteogenic differentiated adipose-derived stem cell (ADSC) loaded beta-tricalcium phosphate (β-TCP) in the restoration of bone defects under intraperitoneal administration of 1α,25-dihydroxyvitamin D3(1α,25(OH)2D3). ADSCs were isolated from the fat tissue of 8 week old Wister rats and co-cultured with β-TCP for 21 days under osteogenic induction. Then the ADSC-β-TCP complexes were implanted into bone defects in the femora of rats.

Local administration of calcitriol positively influences bone remodeling and maturation during restoration of mandibular bone defects in rats.

The aim of this study was to investigate the influence of calcitriol on osteoinduction following local administration into mandibular bone defects. Calcitriol-loaded absorbable collagen membrane scaffolds were prepared using the polydopamine coating method and characterized by scanning electron microscopy. Composite scaffolds were implanted into rat mandibular bone defects in the following groups: no graft material (control), bare collagen membrane (CM group), collagen membrane bearing polydopamine coating (DOP/CM group), and collagen membrane bearing polydopamine coating absorbed with calcitriol (CAL/DOP/CM group).