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Tumor necrosis factor receptor-associated factor 6 is required to inhibit foreign body giant cell formation and activate osteoclasts under inflammatory and infectious conditions.

Osteoclasts and foreign body giant cells (FBGCs) are derived from common progenitors and share properties such as multi-nucleation capacity induced by cell-cell fusion; however, mechanisms underlying lineage determination between these cells remain unclear. Here we show that, under inflammatory conditions, osteoclasts are stimulated in a manner similar to M1 macrophages, while formation of FBGCs, which exhibit M2-like phenotypes, is inhibited in a manner similar to that seen in M1/M2 macrophage polarization. FBGC/osteoclast polarization was inhibited by conditional knockout of tumor necrosis f…

Zoledronic acid induces formation of a pro-apoptotic ATP analogue and isopentenyl pyrophosphate in osteoclasts in vivo and in MCF-7 cells in vitro.

BACKGROUND AND PURPOSE: Bisphosphonates (BPs) are highly effective inhibitors of bone resorption. Nitrogen-containing bisphosphonates (N-BPs … g zoledronic acid in vivo to rabbits, IPP/ApppI formation and accumulation was assessed in isolated osteoclasts. The formation of ApppI from IPP was compared with the metabolism of clodronate in MCF-7 cells in vitro. IPP/ApppI and AppCCl2p levels in cell extracts were analysed by mass spectrometry. KEY RESULTS: Isopentenyl pyrophosphate/ApppI were formed in …

Regulatory mechanisms of miR-212-3p on the secretion of inflammatory factors in monocyte-macrophages and the directed differentiation into osteoclasts in ankylosing spondylitis.

To explore the mechanisms of action of micro ribonucleic acid (miR)-212-3p in the secretion of inflammatory factors in monocyte-macrophages and the directed differentiation into osteoclasts (OCs) in ankylosing spondylitis (AS), proteoglycan was used to establish an AS mouse model. The mouse monocyte-macrophages were cultured in vitro, transfected with miR-212-3p mimic, and added with phosphorylated-extracellular signal-regulated kinase (p-ERK)1/2 agonist Ro67-7476 in vitro. After the cells were transfected with the miR-212-3p mimic in each group, the expressions of p-ERK1/2, matrix metalloprot…

Overexpression of circ_0021739 in Peripheral Blood Mononuclear Cells in Women with Postmenopausal Osteoporosis Is Associated with Reduced Expression of microRNA-194-5p in Osteoclasts.

BACKGROUND Postmenopausal osteoporosis, a common disease among elderly women, is linked to estrogen deficiency, mechanical loading, and geno … sion of hsa_circ_0021739 decreased the level of hsa-miR-502-5p and inhibited the differentiation of osteoclasts. CONCLUSIONS The circRNA hsa_circ_0021739 is a potential blood biomarker for postmenopausal osteoporosis. In addition, hsa-miR-502-5p is a likely target of hsa_circ_0021739, which acts to regulate the differentiation of osteoclasts.

Osteoblasts from the toothless (osteopetrotic) mutation in the rat are unable to direct bone resorption by normal osteoclasts in response to 1,25-dihydroxyvitamin D.

Osteopetrosis describes a diversified group of metabolic bone disorders characterized by a generalized, skeletal sclerosis resulting from reduced osteoclast-mediated bone resorption. The toothless (tl) osteopetrotic mutation in the rat is characterized by few osteoclasts and the inability to be cured by transplants of hemopoietic stem cells. This implies that the defect(s) responsible for reduced osteoclast activity in tl rats is within the skeletal microenvironment (cells or matrices). Osteoblasts and their products are known to play a role in regulating bone resorption and abnormalities in t…

Celastrol attenuates osteoclast-driven bone invasion in pituitary adenomas and suppresses HSP90AA1/TRAF6/NF-κB signaling.

Bone-invasive pituitary adenomas (BIPAs) are associated with skull base destruction, incomplete resection and postoperative recurrence, but pharmacological strategies targeting tumor-induced osteolysis remain limited. Here, we investigated whether celastrol, a bioactive triterpenoid from Tripterygium wilfordii, restrains BIPA progression by modulating macrophage-associated osteoclastogenesis. Clinical recurrence analysis, calvarial pituitary adenoma bone invasion models, micro-CT, histology, immunofluorescence, cell functional assays, osteoclast differentiation assays, RNA sequencing, molecula

Hyperglycemia differentially regulates osteoblast and osteoclast autophagy via AMPK/mTOR/p70 S6K signaling in diabetic osteoporosis.

Type 2 diabetes mellitus (T2DM) often induces diabetic osteoporosis (DOP) with impaired bone remodeling, yet its underlying mechanism remain … tophagy, and impaired mineralization as well as alkaline phosphatase (ALP) activity; conversely, in osteoclasts, HG enhanced autophagy through the inverse regulatory pathway and accelerated osteoclast differentiation and bone resorption. Collectively, these findings illustrate that hyperglycemia disrupts bone homeostasis via cell-type-specific regulation of A …

Rapid generation of dental pulp stem cell-derived mineralized extracellular matrix for quantitative osteoclast resorption assays.

Osteoclasts are large, multinucleated cells responsible for bone resorption, playing a central role in bone development, remodeling, and the pathogenesis of metabolic bone diseases through the degradation of inorganic hydroxyapatite and the organic matrix which is primarily composed of collagen. In the study of osteoclast biology, quantitative evaluation of bone resorption capacity is a key indicator of functional maturation. However, currently available assays largely rely on natural bone substrates, such as large animal teeth, or synthetic mineralized materials, both of which present limitat…

A Fully Human Engineered Bone Niche With Endogenous Osteoclastogenesis Reveals Osteoclast-Dependent Osteomimicry in Prostate Cancer Cells.

Bone is the predominant site of metastasis in advanced prostate cancer (PCa), yet the mechanisms governing tumor-bone interactions remain incompletely understood, thanks in part to the scarcity of relevant models. The role played by osteoclasts in such interactions is especially obscure. A modular human three-dimensional (3D) in vitro bone niche model was developedThe model integrates osteoblasts and osteoclasts within a mineralized scaffold, recreating an endosteal-like microenvironment for co-culture with PCa cell lines and patient-derived organoids (PDOs). The engineered construct maintains…

Roburic acid inhibits glucocorticoid-induced osteonecrosis of the femoral head associated osteoclast activity via targeting PTP1B.

BACKGROUND: Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) has unclear pathogenesis and lacks effective therapies. Protei … TSK/PTP1B co-immunofluorescence in order to analyze PTP1B protein level and its colocalization with osteoclasts. For animal experiments, mouse bone marrow-derived macrophages (BMMs) were induced with dexamethasone (DEX) and RANKL to mimic GIONFH-related osteoclast hyperactivity, and RA was then administered. Target validation was performed via molecular docki …

M2 Polarization of RAW264.7-Derived Exosomes Inhibits Osteoclast Differentiation and Inflammation via PKM2/HIF-1α Axis.

BACKGROUND: Periodontitis (PD) is a chronic inflammatory disease characterized by alveolar bone loss, primarily driven by excessive osteoclast differentiation and activation. Exosomes derived from M2 macrophages have been implicated in the pathological progression of various diseases, including PD. Pyruvate kinase (PK)M2, a key metabolic enzyme, promotes inflammation in periodontal disease through enhanced production of pro-inflammatory cytokines. This study investigated whether M2 macrophage-derived exosomes regulate osteoclast differentiation and contribute to PD progression. METHODS: Exoso

Fe₃O₄-MXene as a dual-function root canal agent for disinfection and osteoclast inhibition in persistent apical periodontitis.

Persistent apical periodontitis (PAP) is characterized by periapical inflammation and alveolar bone resorption resulting from microorganisms that are resistant to conventional root canal disinfection. The treatment goals for PAP are to effectively eliminate resistant microorganisms and inhibit bone resorption. Root canal therapy (RCT) is the primary treatment for PAP, with chemical disinfection being a fundamental step in the process. This study developed Fe3O4‒MXene, a new root canal disinfectant with photothermally induced antibacterial properties and the potential to inhibit bone resorption

(D-Ala2)GIP Inhibits TNF-α-Induced Osteoclast Formation and Bone Resorption, and Orthodontic Tooth Movement.

The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) promotes insulin secretion, lowers blood glucose levels, and is incr … After 12 days, the (D-Ala2)GIP-treated group showed significantly reduced tooth movement and fewer osteoclasts and odontoclasts on the compression side compared to the PBS control. These findings suggest that (D-Ala2)GIP inhibits OTM, potentially by suppressing TNF-α-driven osteoclastogenesis and bone resorption.

DC-STAMP and OC-STAMP cooperatively regulate osteoclast and foreign body giant cell cell-cell fusion.

INTRODUCTION: Osteoclasts and foreign body giant cells (FBGCs) are multi-nuclear cells established by fusion of their mono-nuclear forms. Multi-nucleation via cell-cell fusion is a common characteristic of osteoclasts and FBGCs, and Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) and Osteoclast Stimulatory Transmembrane Protein (OC-STAMP) are both required for the process. Thus, it is thought that DC-STAMP and OC-STAMP interaction likely induces this fusion, but details of these mechanisms are not clear. MATERIALS AND METHODS: We crossed DC-STAMP knockout (KO) with OC-STAMP KO mice t…

Bovine collagen peptides and peptide-calcium complexes inhibit RANKL-induced osteoclast differentiation in RAW 264.7 macrophages.

BACKGROUND: This study aims to prepare collagen peptides from bovine bone meal using a combination of heat pretreatment and enzymatic digestion, and to chelate them with calcium chloride to form peptide-calcium chelates. The effects of both on the proliferation and differentiation of osteoclasts were investigated using cellular experiments (RAW 264.7 cells). RESULTS: Both bovine collagen peptides and their calcium chelates (BPs, HBPs, BPs-Ca, and HBPs-Ca) can significantly inhibit the RANKL-induced differentiation of RAW 264.7 cells into osteoclasts. The preheating treatment before enzymatic …

Inflammatory macrophage-derived itaconate inhibits DNA demethylase TET2 to prevent excessive osteoclast activation in rheumatoid arthritis.

Itaconate, a macrophage-specific anti-inflammatory metabolite, has recently emerged as a critical regulator in rheumatoid arthritis pathogenesis. We found that itaconate is a TNF-α responsive metabolite significantly elevated in the serum and synovial fluid of rheumatoid arthritis patients and we demonstrated that itaconate is primarily produced by inflammatory macrophages rather than osteoclasts or osteoblasts. In TNF-transgenic and Irg1-/- hybrid mice, a more severe bone destruction phenotype was observed. Administration of itaconate prevents excessive activation of osteoclasts by inhibiting…

KIAA1429-mediated M6A methylation inhibits osteoclast differentiation via stabilizing Lrp4 mRNA and protects against osteoporosis.

N6-methyladenosine (m6A) is a novel epigenetic modification that has been reported to be involved in the progression of osteoporosis (OP), providing new insights into the pathogenesis of OP. The methyltransferases KIAA1429 [also known as virus-like m6A methyltransferase-associated protein (VIRMA)] participates in various essential biological processes by regulating target gene expression levels. However, the function of KIAA1429-mediated m6A modification in OP progression remains unclear. This study aimed to investigate the biological roles and potential underlying mechanisms of KIAA1429 in OP

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… Meanwhile, the RAW264.7 cells and BMDM that were induced to differentiate toward osteoclasts showed notably reduced Lrp4 mRNA expression in osteoclasts (Fig. 4 H). … In vivo experiments showed that Kiaa1429 overexpression did not rescue bone mass and inhibit osteoclast differentiation in osteoclast-specific Lrp4 knockout OVX mice, which further suggested that Lrp4 was a downstream target gene of KIAA1429 in osteoclasts. …

A microprotein encoded by LINC00263 promotes breast cancer osteolytic bone metastasis by inducing osteoclastogenesis and inhibiting osteoclast ferroptosis.

Currently, there are no effective prevention or therapeutic methods for breast cancer bone metastasis (BC-BM), which leading to severe skele … ssociated protein 1 (YAP1) pathway, which enhanced osteoclastogenesis and diminishes ferroptosis in osteoclasts, thereby creating an osteolytic bone metastasis niche that fosters BC-BM. Importantly, treatment with angoroside C, an active component from the traditional Chinese medicine Scrophulariae Radix extract, effectively blocked the binding of LINC00263-P …

Case of Undifferentiated Carcinoma with Osteoclast-like Giant Cells Associated with a Mucinous Cystic Neoplasm of the Pancreas: A Diagnostic Conundrum.

Undifferentiated carcinoma with osteoclast-like giant cells (UC-OGC) is a rare histological subtype of pancreatic ductal adenocarcinoma according to the World Health Organization classification of digestive system tumors. This subtype is exceptionally uncommon, accounting for less than 1% of pancreatic malignant tumors. This paper presents a rare case of a 62-year-old female patient diagnosed with UC-OGC. The patient initially presented with symptoms, including epigastric pain and the presence of an abdominal mass, which led to further investigation and the eventual diagnosis of this unusual a

Small nucleolar RNA host gene 5 plays a role in orthodontic tooth movement by inhibiting osteoclast differentiation.

BACKGROUND AND OBJECTIVES: The alveolar bone remodelling promoted by reasonable mechanical force triggers orthodontic tooth movement (OTM). The generation of osteoclasts is essential in this process. However, the mechanism of mechanical force mediating osteoclast differentiation remains elusive. Small nucleolar RNA host gene 5 (SNHG5), which was reported to mediate the osteogenic differentiation of bone marrow mesenchymal stem cells in our previous study, was downregulated in human periodontal ligament cells (hPDLCs) under mechanical force. At the same time, the RANKL/OPG ratio increased. Base…