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Ano5 deficiency disturbed bone formation by inducing osteoclast apoptosis in Gnathodiaphyseal dysplasia.

Gnathodiaphyseal dysplasia (GDD) is a rare genetic syndrome characterized by cemento-ossifying fibroma lesions in the mandible and sclerosis … ular calcium concentration ([Ca2+]i) and calcium transients were significantly decreased in Ano5-/- osteoclasts accompanied by abnormally altered expression of calcium transporters, resulting in calcium dyshomeostasis. In addition, the endoplasmic reticulum stress (ERS) response was significantly enhanced in Ano5-/- osteoclasts, possibly because of calcium dy …

Targeting chaperone-mediated autophagy to regulate osteoclast activity as a therapeutic strategy for osteoporosis.

Osteoporosis is an age-related bone metabolic disease characterized by a persistent bone mass decrease and bone structure destruction. Osteoclasts, important cells in the bone remodelling process, are closely associated with the onset and progression of osteoporosis; however, the regulatory mechanisms involved remain unclear. In this study, TFE3 cytoplasmic translocation inhibited LAMP2A expression in osteoclasts and precursors in elderly individuals with osteoporosis and the downregulation of LAMP2A expression mediated the attenuation of chaperone-mediated autophagy (CMA). This inhibition pre…

A microenvironment responsive nanoparticle regulating osteoclast fate to promote bone repair in osteomyelitis.

Osteomyelitis exhibits bone defects in an inflammatory and acid microenvironment. As a crucial factor in this inflammation responses, the ma … tory microenvironment. Intracellularly, it impacted the formation, function, and differentiation of osteoclasts through the macrophage-osteoclast axis, thereby promoting bone defect repair. In vivo and in vitro studies showed GNPs-BMP9@TA-Ce regulated osteoclasts to optimize osteomyelitis treatment strategies, highlighting the potential of modified nanobiomat …

Trim21 deficiency alleviates osteoporosis by inhibiting osteoclast differentiation through regulating Txnip.

OBJECTIVE: The tripartite motif containing 21 (Trim21), an E3 ubiquitin ligase, plays a crucial role in the progression of various skeletal diseases, particularly in osteoporosis. In our previous study, Trim21 deficiency was shown to exert dual effects by suppressing bone resorption and enhancing osteogenesis. However, the specific mechanism by which Trim21 inhibits osteoclast (OC) differentiation remains unclear. In this study, we utilized a myeloid cell-specific conditional knockout model of Trim21 to investigate the underlying regulatory mechanisms. METHODS: OC-specific Trim21 knockout mic

Murine Osteoblast and Osteoclast Co-culture on Demineralized Bone Paper for Bone Remodeling.

Continuous and balanced bone remodeling is essential for maintaining mechanical integrity, mineral homeostasis, and hematopoiesis. Dysregula … cellular matrix (ECM) and the dynamic interplay between bone-forming osteoblasts and bone-resorbing osteoclasts. Recently, we developed an osteoid-mimicking demineralized bone paper (DBP) by thin-sectioning demineralized bovine compact bone matrix. DBP supports osteoblastic mineral deposition and the subsequent transition to bone-lining cells. When co-culture …

U0126 induces osteoclast differentiation via the p38-NFATc-1 signaling pathway.

Osteoclast differentiation plays an important role in bone metabolic diseases, such as osteoporosis, osteosclerosis and so on. In the study, we found that the ERK inhibitor, U0126, significantly increased the number of multinucleated osteoclasts after inducing differentiation of mouse mononuclear macrophage RAW264.7 cells. The Shh-p38-NFATc-1 signaling pathway has been reported to induce osteoclast differentiation in our previous work, and here U0126 also could increase pp38 and NFATc-1 expression as well as NFATc-1 entrance into the nucleus. Animal experiment demonstrated that U0126 accelerat…

Heat-killed Lancefieldella Rimae Induces Bone Resorption by Promoting Osteoclast Differentiation.

INTRODUCTION: Apical periodontitis, mainly caused by bacterial infection in the dental pulp, is often accompanied by abscess, periapical inflammation, and alveolar bone loss. Lancefieldella rimae has been detected in the root canals of patients with apical periodontitis. Here, we investigated whether L. rimae is associated with bone resorption. METHODS: L. rimae was anaerobically cultured and heat-killed (HKLr). A mouse calvarial implantation model was used to determine the bone resorption in vivo. Committed osteoclasts prepared from C57BL/6 wild-type or Toll-like receptor 2 (TLR2)-deficient …

Undifferentiated carcinoma of the pancreas with osteoclast-like giant cells, a two cases report.

INTRODUCTION AND IMPORTANCE: Fine needle aspiration is the standard method for the pathological evaluation of pancreatic masses. In the following context, rare variants of such masses might present a challenge. Our goal is to describe the clinical, cytological, and histological findings of two cases of undifferentiated carcinoma with osteoclast-like giant cells (UCOCGC) a rare variant of pancreatic ductal adenocarcinoma (PDAC). CASE PRESENTATION: Two cases were identified. Cytological findings exhibit similarities between the two cases. One patient received multiple chemotherapy regimens and

Local re-activation of osteoclast differentiation as a novel therapeutic strategy for osteonecrosis of the jaw.

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… precursors into osteoclasts. … This possibility should be experimentally tested in a RANKL-dependent osteoclast differentiation model. …

The role of TRPV2 as a regulator on the osteoclast differentiation during orthodontic tooth movement in rats.

When orthodontic forces are applied to teeth, bone remodeling, which consists of bone resorption and bone formation, occurs around the teeth. Transient receptor potential vanilloid 2 (TRPV2) is a cation channel expressed in various cell types that responds to various stimuli, including mechanical stress, and involved in calcium oscillations during the early stages of osteoclast differentiation. However, in vivo expression of TRPV2 in osteoclasts has not yet been reported, and temporo-spatial expression of TRPV2 during osteoclast differentiation is unclear. In this study, we examined the TRPV2 …

New insights into inflammatory osteoclast precursors as therapeutic targets for rheumatoid arthritis and periodontitis.

Rheumatoid arthritis (RA) and periodontitis are chronic inflammatory diseases leading to increased bone resorption. Preventing this inflamma … resorption in distant inflamed joints. Interestingly, in inflammatory conditions, the existence of osteoclasts distinct from "classical osteoclasts" has recently been reported. They have proinflammatory origins and functions. Several populations of osteoclast precursors have been described in RA, such as classical monocytes, a dendritic cell subtype, and art …

Lactobacillus rhamnosus inhibits osteoclast differentiation by suppressing the TLR2/NF-κB pathway.

OBJECTIVE: This study aimed to investigate the role of ultrasonicated Lactobacillus rhamnosus extract in osteoclast differentiation and its underlying mechanism, providing new strategies for the treatment of periodontitis. MATERIALS AND METHODS: Osteoclasts were induced using macrophage colony-stimulating factor and receptor activator for nuclear factor-κB ligand. Lactobacillus rhamnosus extracts were obtained via ultrasonic crushing and ultracentrifugation. The effects of the LGG extract on osteoclast differentiation were evaluated, and the related signaling pathways were examined using west…

Invasive breast carcinoma with osteoclast-like stromal giant cells: A case report.

BACKGROUND: Invasive breast carcinoma with osteoclast-like stromal giant cells (OGCs) is an extremely rare morphology of breast carcinomas. To the best of our knowledge, the most recent case report describing this rare pathology was published six years ago. The mechanism controlling the development of this unique histological formation is still unknown. Further, the prognosis of patients with OGC involvement is also controversial. CASE SUMMARY: We report the case of a 48-year-old woman, who presented to the outpatient department with a palpable, growing, painless mass in her left breast for a

PINK1 restrains periodontitis-induced bone loss by preventing osteoclast mitophagy impairment.

The oral colonization of periodontal pathogens onto gingival tissues establishes hypoxic microenvironment, often disrupting periodontal home … on and travecular thickness were lower in Pink1 KO compared to WT mice. The number of TRAP-positive osteoclasts was markedly increased in the periodontal tissues of Pink1 KO mice with LIP. The genetic silencing or deletion of Pink1 promoted excessive osteoclast differentiation and bone resorption in vitro, as respectively indicated by TRAP staining and resorp …

Suppression of IRF9 Promotes Osteoclast Differentiation by Decreased Ferroptosis via STAT3 Activation.

Osteoporosis is a chronic disease that endangers the health of the elderly. Inhibiting osteoclast hyperactivity is a key aspect of osteoporosis prevention and treatment. Several studies have shown that interferon regulatory factor 9 (IRF9) not only regulates innate and adaptive immune responses but also plays an important role in inflammation, antiviral response, and cell development. However, the exact role of IRF9 in osteoclasts has not been reported. To elucidate the role of IRF9 in osteoclast differentiation, we established the ovariectomized mouse model of postmenopausal osteoporosis and …

Osteopetrosis associated with PLEKHM1 and SNX10 genes, both involved in osteoclast vesicular trafficking.

The clinical and radiological variability seen in different forms of osteopetrosis, all due to impaired osteoclastic bone resorption, reflect many causal genes. Both defective differentiation of osteoclasts from hematopoietic stem cells as well as disturbed functioning of osteoclasts can be the underlying pathogenic mechanism. Pathogenic variants in PLEKHM1 and SNX10 can be classified among the latter as they impair vesicular transport within the osteoclast and therefore result in the absence of a ruffled border. Some of the typical radiological hallmarks of osteopetrosis can be seen, and most…

IL-10 inhibits osteoclast differentiation and osteolysis through MEG3/IRF8 pathway.

OBJECTIVE: Osteolysis caused by wear particles is the main reason for joint replacement failure. Inhibition of osteoclast differentiation relieves wear particle-induced osteolysis. Our study aimed to explore the effect of lncRNA maternally expressed gene 3 (MEG3) on osteoclast differentiation and wear particle-induced osteolysis, and to improve the potential mechanism of interleukin-10 (IL-10) inhibition on osteoclast differentiation. METHODS: Polymethylmethacrylate (PMMA) -induced osteolysis mice model and receptor activator of nuclear factor-B ligand (RANKL) -induced osteoclast differentiat

CST6 suppresses osteolytic bone disease in multiple myeloma by blocking osteoclast differentiation.

Osteolytic bone disease is a hallmark of multiple myeloma (MM). A significant fraction (~20%) of MM patients do not develop osteolytic lesions (OLs). The molecular basis for the absence of bone disease in MM is not understood. We combined PET-CT and gene expression profiling (GEP) of purified BM CD138+ MM cells from 512 newly diagnosed MM patients to reveal that elevated expression of cystatin M/E (CST6) was significantly associated with the absence of OL in MM. An enzyme-linked immunosorbent assay revealed a strong correlation between CST6 levels in BM serum/plasma and CST6 mRNA expression. B

Mechanism of Huangqi Sanxian Decoction Inhibiting Osteoclast Differentiation Based on Network Pharmacology.

Osteoclasts (OCs) have been the unique cell type exhibiting the bone-resorption activity in body. It is important to identify drugs to resist osteoclastogenesis to manage the bone-loss disorders. Huangqi Sanxian decoction (HQSXD) is utilized for the treatment of postmenopausal osteoporosis (PMOP) for a long history in East Asia. This work aimed to examine HQSXD's activity in OC differentiation. Based on staining with tartrate-resistant acid phosphatase (TRAP), it was found that HQSXD suppressed OC generation under the induction of RANKL produced in the bone marrow-derived monocytes/macrophages…

The osteoclast-type giant cell rich carcinoma of urinary bladder: A case series.

BACKGROUND: Osteoclast-type giant cell-rich carcinomas (OGCRCs) of urinary bladder are extremely rare, aggressive tumors that are often diagnosed as undifferentiated carcinomas. The morphology overlaps with other giant cell-rich benign and malignant bladder lesions. Little is known about the pathogenesis and clinical management of this aggressive variant. The aim of this study was to review clinico-pathologic features, and survival characteristics in a series of OGCRCs. MATERIALS AND METHODS: Five cases of OGCRCs of bladder were retrospectively reviewed. Clinical presentation, histomorphology