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Isolation and characterization of highly enriched, prefusion mouse osteoclastic cells.

This study describes the isolation and characterization of highly enriched mammalian osteoclast precursors, released by the "disintegrin" ec … were mostly mononucleated and based on the following characteristics are considered to be prefusion osteoclasts (pOC cells): (i) presence of calcitonin (CT) receptors documented by 125I-sCT autoradiography and cAMP generation in response to salmon calcitonin; (ii) expression of mRNAs for alpha v beta 3 integrin, osteopontin, 92-kDa type IV collagenase (matrix …

Mycotrienins. A new class of potent inhibitors of osteoclastic bone resorption.

Pharmacological intervention using selective tyrosine kinase inhibitors has been shown to be an effective approach to inhibit osteoclast function. Here, we report on the structure-activity relations of benzoquinone ansamycins isolated from Streptomyces rishirensis, which form a new class of potent inhibitors of osteoclast-mediated bone resorption. Parathyroid hormone-stimulated bone resorption was inhibited concentration dependently by both mycotrienin I and mycotrienin II, showing half-maximal inhibition in the low nanomolar range in fetal rat long bones in vitro. Structure-activity relation

Evidence that c-src is involved in the process of osteoclastic bone resorption.

Transgenic mice lacking a functional c-src gene have osteopetrosis, a bone disorder characterized by defective osteoclast function. We have investigated the effects of selective protein tyrosine kinase inhibitors that are known to inhibit c-src, on osteoclast activity in the bone slice assay. Geldanamycin, herbimycin A and monorden (0.001-10 microM) all dose-dependently inhibited bone resorption with IC50 values of 8, 70 and 86 nM, respectively. At concentrations of 0.001-1 microM, the compounds were not cytotoxic as judged by osteoclast morphology and survival on bone slices. In order to dete

Osteoclastic inhibition: an action of nitric oxide not mediated by cyclic GMP.

The osteoclast is unique in its ability to resorb bone, and excessive osteoclastic activity has been implicated in osteoporosis, Paget disea … pe changes were associated with a reduction of bone resorption after a 24-hr incubation of isolated osteoclasts on devitalized bone slices. NO is thought to act by stimulating guanylate cyclase, with a consequent increase in cyclic GMP, but a different mode of action is likely in the osteoclast since dibutyryl or 8-bromo cyclic GMP have no effect. It should b …

Reduced life span of the osteoclast in osteopetrotic (mi and midi) mice.

Osteoclasts were enumerated on the parietal bones of mice carrying combinations of alleles (mi, midi and +) at the microphthalmic locus. Homozygous mutants at this locus show varying degrees of osteopetrosis due to defective bone resorption. As the severity of the bone resorption defect increased across the genotypes, there was an increase in the total number of osteoclasts and also an increase in the proportion of uninucleate osteoclasts. In parietal bones incubated for 24 h with parathyroid hormone (PTH) there was no significant difference between osteopetrotic and normal bones in terms of t…

Osteoblast and osteoclast cell number and cell activity in postmenopausal osteoporosis.

This study evaluates osteoblast and osteoclast cell numbers and cell activities determined from quantitative histology of trabecular bone in human iliac crest bone biopsies. Subjects studied were postmenopausal osteoporotic patients (aged 53-81) for whom total body calcium and urine and serum clinical data were also available. Only 39% of the osteoclasts identified by acid phosphatase content were multinucleate; however, a significant correlation between multinucleate osteoclasts and the total number of osteoclasts was found (r = 0.87; p less than 0.001). The mean number of osteoclasts per squ…

Osteoclast abnormalities in idiopathic osteopetrosis. Reference to the ultrastructural histochemistry study.

In order to investigate skeletal abnormalities in a case of idiopathic osteopetrosis, a bone biopsy was taken from the anterior iliac crest and prepared for ultrastructural and histochemical study. There was a drastic reduction in osteoclastic bone resorption. The ruffle border and sealing zone, which are the osteoclast cell surface markers of bone resorption, were absent. The cells were highly vacuolated, and the vacuoles contained large amounts of a residual organic material which reacted strongly with acid phosphatase. Acid phosphatase activity was never found outside the cell, and in parti

Correction: Punicalin attenuates breast cancer-associated osteolysis by inhibiting the NF-κB signaling pathway of osteoclasts.

[This corrects the article DOI: 10.3389/fphar.2021.789552.].

Sema3A Restores Bone Homeostasis in Peri-Implantitis by Activating Osteoblasts and Suppressing Osteoclasts via PI3K/AKT.

BACKGROUND: Peri-implantitis, a major cause of implant failure, is driven by disrupted bone homeostasis. Semaphorin 3A (Sema3A) bidirectionally regulates bone remodelling, yet its role in peri-implantitis remains poorly defined. This study aimed to elucidate the mechanisms by which Sema3A modulates bone homeostasis in peri-implantitis. MATERIALS AND METHODS: Single-cell transcriptomic analysis (GSE171213) was performed on a periodontitis-derived periodontal tissue dataset to characterize bone-related cell communication. A murine peri-implantitis model was established via silk ligation, and bo

Inhibition of soluble epoxide hydrolase reverses bone loss in periodontitis by upregulating EMCN and inhibiting osteoclasts.

BACKGROUND: Improving the microenvironment to augment endogenous regenerative potential has emerged as a fundamental concept for stimulating … ther verified the effects of TPPU on inhibiting neutrophil adhesion and inflammation and inhibiting osteoclasts. RESULTS: Our in vitro experiments demonstrated that TPPU enhances the interaction between mesenchymal stem cells and vascular endothelial cells to enhance anti-inflammatory and osteogenic differentiation effects and revealed a new anti-inflammator …

Zingerone attenuates Ti particle-induced inflammatory osteolysis by suppressing the NF-κB signaling pathway in osteoclasts.

Aseptic loosening caused by inflammatory osteolysis is one of the most frequent and serious long-term complications after total joint arthroplasty (TJA). Development of a new therapeutic drug is required due to the lack of effective therapy and serious adverse effects. This study aimed to explore the pharmacological properties of zingerone (ZO) in attenuating osteoclast-mediated periprosthetic osteolysis and how ZO modulates osteoclastogenesis. The nontoxic concentration of ZO was clarified by the CCK-8 method. Then, we explored the efficacy of ZO on suppressing osteoclast differentiation, F-a

CRISPR/Cas13d targeting GZMA in PARs pathway regulates the function of osteoclasts in chronic apical periodontitis.

Chronic apical periodontitis is a prevalent oral disease characterized by bone loss, and its underlying mechanisms remain unclear. This study aimed to investigate the role and mechanism of the serine protease GZMA in osteoclasts during chronic apical periodontitis. To address this, we employed crRNA/Cas13d to inhibit GZMA expression and examined its impact on osteoclast behavior. Our findings revealed that GZMA plays a significant role in promoting osteoclast cell proliferation while inhibiting cell apoptosis. Additionally, the inhibition of GZMA led to a notable increase in miR-25-3p expressi…

Ionizing Radiation Activates Mitochondrial Function in Osteoclasts and Causes Bone Loss in Young Adult Male Mice.

The damaging effects of ionizing radiation (IR) on bone mass are well-documented in mice and humans and are most likely due to increased osteoclast number and function. However, the mechanisms leading to inappropriate increases in osteoclastic bone resorption are only partially understood. Here, we show that exposure to multiple fractions of low-doses (10 fractions of 0.4 Gy total body irradiation [TBI]/week, i.e., fractionated exposure) and/or a single exposure to the same total dose of 4 Gy TBI causes a decrease in trabecular, but not cortical, bone mass in young adult male mice. This damagi

Complement C3a activates osteoclasts by regulating the PI3K/PDK1/SGK3 pathway in patients with multiple myeloma.

ObjectiveMyeloma bone disease (MBD) is the most common complication of multiple myeloma (MM). Our previous study showed that the serum levels of C3/C4 in MM patients were significantly positively correlated with the severity of bone disease. However, the mechanism of C3a/C4a in osteoclasts MM patients remains unclear.MethodsThe formation and function of osteoclasts were analyzed after adding C3a/C4a in vitro. RNA-seq analysis was used to screen the potential pathways affecting osteoclasts, and the results were verified by Western blot, qRT-PCR, and pathway inhibitors.ResultsThe osteoclast area…

p300/CBP inhibitor A-485 inhibits the differentiation of osteoclasts and protects against osteoporotic bone loss.

Osteoporosis is one of the most common metabolic bone diseases among pre- and post-menopausal women. Despite numerous advances in the treatm … ast differentiation in vitro by reducing the number of tartrate-resistant acid phosphatase-positive osteoclasts without inducing significant cytotoxicity. In particular, A-485 dose-dependently disrupted F-actin ring formation and downregulated the expression of genes associated with osteoclast differentiation, such as CTSK, c-Fos, TRAF6, VATPs-d2, DC-STAMP, a …

Influence of the TGF-β Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions.

The balance between bone forming cells (osteoblasts/osteocytes) and bone resorbing cells (osteoclasts) plays a crucial role in tissue homeostasis and bone repair. Several hormones, cytokines, and growth factors-in particular the members of the TGF-β superfamily such as the bone morphogenetic proteins-not only regulate the proliferation, differentiation, and functioning of these cells, but also coordinate the communication between them to ensure an appropriate response. Therefore, this review focuses on TGF-β superfamily and its influence on bone formation and repair, through the regulation of …

Sfrp4 repression of the Ror2/Jnk cascade in osteoclasts protects cortical bone from excessive endosteal resorption.

Loss-of-function mutations in the Wnt inhibitor secreted frizzled receptor protein 4 (SFRP4) cause Pyle's disease (OMIM 265900), a rare skeletal disorder characterized by wide metaphyses, significant thinning of cortical bone, and fragility fractures. In mice, we have shown that the cortical thinning seen in the absence of Sfrp4 is associated with decreased periosteal and endosteal bone formation and increased endocortical resorption. While the increase in Rankl/Opg in cortical bone of mice lacking Sfrp4 suggests an osteoblast-dependent effect on endocortical osteoclast (OC) activity, whether

Emerging Roles of Osteoclasts in the Modulation of Bone Microenvironment and Immune Suppression in Multiple Myeloma.

Multiple myeloma (MM) is one of the most common forms of hematologic malignancy resulting from cancerous proliferation of mature malignant plasma cells (MPCs). But despite the real improvement in therapeutics in the past years, it remains largely incurable. MM is the most frequent cancer to involve bone due to the stimulation of osteoclast (OCL) differentiation and activity. OCLs have a unique capacity to resorb bone. However, recent studies reveal that they are not restrained to this sole function. They participate in the control of angiogenesis, medullary niches, and immune responses, includ

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… Functional osteoclast-like transformation of cultured human myeloma cell lines . … Roles of osteoclasts in the control of medullary hematopoietic niches . …

Early reversal cells in adult human bone remodeling: osteoblastic nature, catabolic functions and interactions with osteoclasts.

The mechanism coupling bone resorption and formation is a burning question that remains incompletely answered through the current investigations on osteoclasts and osteoblasts. An attractive hypothesis is that the reversal cells are likely mediators of this coupling. Their nature is a big matter of debate. The present study performed on human cancellous bone is the first one combining in situ hybridization and immunohistochemistry to demonstrate their osteoblastic nature. It shows that the Runx2 and CD56 immunoreactive reversal cells appear to take up TRAcP released by neighboring osteoclasts.…

Effect of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) on the expression of EphA2 in osteoblasts and osteoclasts.

Porphyromonas gingivalis (Pg) as the major pathogenic bacterium of chronic periodontitis can cause alveolar bone resorption. Lipopolysaccharide (LPS) is its main virulence factor. The Eph family plays an important role in maintaining bone homeostasis. In this study, the effects of P. gingivalis lipopolysaccharide (Pg-LPS) on the expression of EphA2 in osteoblasts and osteoclasts were investigated. MC3T3-E1 cells and RAW264.7 cells were separately cultured in osteoblast-conditioned medium and osteoclast-conditioned medium to induce their differentiation into osteoblasts and osteoclasts, respect…