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Osteoblast-Osteoclast Coculture Amplifies Inhibitory Effects of FG-4592 on Human Osteoclastogenesis and Reduces Bone Resorption.

The link between bone and blood vessels is regulated by hypoxia and the hypoxia-inducible transcription factor, HIF, which drives both osteogenesis and angiogenesis. The recent clinical approval of PHD enzyme inhibitors, which stabilize HIF protein, introduces the potential for a new clinical strategy to treat osteolytic conditions such as osteoporosis, osteonecrosis, and skeletal fracture and nonunion. However, bone-resorbing osteoclasts also play a central role in bone remodeling and pathological osteolysis, and HIF promotes osteoclast activation and bone loss in vitro. It is therefore likel…

Effect of ProRoot MTA® and Biodentine® on osteoclastic differentiation and activity of mouse bone marrow macrophages.

OBJECTIVES: This investigation aimed to assess the differentiation inhibitory effects of ProRoot MTA® (PMTA) and Biodentine® (BIOD) on osteoclasts originated from murine bone marrow macrophages (BMMs) and compare these effects with those of alendronate (ALD). MATERIALS AND METHODS: Mouse BMMs were cultured to differentiate into osteoclasts with macrophage colony-stimulating factor and receptor activator of NF-κB (RANKL), treated with lipopolysaccharide. After application with PMTA, BIOD, or ALD, cell toxicities were examined using WST-1 assay kit, and RANKL-induced osteoclast differentiation …

TNF-α is responsible for the contribution of stromal cells to osteoclast and odontoclast formation during orthodontic tooth movement.

Compressive force during orthodontic tooth movement induces osteoclast formation in vivo. TNF-α plays an important role in mouse osteoclast … ement was evaluated and tartrate-resistant acid phosphatase-positive cells along the alveolar bone (osteoclasts) and along the tooth root (odontoclasts) were counted after 12 days of tooth movement. The amount of orthodontic tooth movement, and the number of osteoclasts and odontoclasts on the compression side were significantly lower in WT>KO and KO>KO mice …

Alveolar Bone Osteoclast Profile in the Periodontitis Wistar Rats Model with the Snail Slime (Achatina Fulica) Application.

BACKGROUND: Bone damage is a result of periodontal disease that occurs due to changes in osteoclast and osteoblast activity in response to local inflammation. The bacteria Aggregatibacter actinomycetemcomitans produces Lipopolysaccharide (LPS), which can increase osteoclast activity. AIM: This study aimed to analyse the decrease in alveolar bone osteoclasts in periodontitis rats' model with the application of snail slime. METHODS: Wistar rats (27) with periodontitis divided into three groups, namely the control group (debridement), P1 group (debridement and application of oral snail slime) 3…

Aspirin inhibits RANKL-induced osteoclast differentiation in dendritic cells by suppressing NF-κB and NFATc1 activation.

BACKGROUND: Aspirin has been demonstrated to promote osteoblast-mediated bone formation and inhibit osteoclast (OC)-mediated bone resorption … had favorable therapeutic effects on bone regeneration in the bone defect model, and the number of osteoclasts was decreased. CONCLUSIONS: Aspirin inhibited RANKL-induced OC differentiation in DCs via the NF-κB pathway, downregulating expression of NFATc1. Aspirin treatment promoted bone regeneration by inhibiting DDOC activation in the early stages of infl …

The Bone Marrow Edema Links to an Osteoclastic Environment and Precedes Synovitis During the Development of Collagen Induced Arthritis.

Objectives: To determine the relationship between bone marrow edema (BME), synovitis, and bone erosion longitudinally using a collagen induced arthritis mice (CIA) model and to explore the potential pathogenic role of BME in bone erosion. Methods: CIA was induced in DBA/1J mice. BME and corresponding clinical symptoms of arthritis and synovitis during the different time points of CIA development were assayed by magnetic resonance imaging (MRI), arthritis sore, and histologic analyses. The expression of osteoclasts (OCs), OCs-related cytokines, and immune cells in bone marrow were determined by…

GPDPLQ1237-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro.

C-telopeptide of type II collagen (CTX-II) has been shown to be a highly relevant biomarker of cartilage degradation in human rheumatic diseases, if measured in synovial fluid or urine. However, serum or plasma CTX-II have not been demonstrated to have any clinical utility to date. Here, we describe the GPDPLQ1237 ELISA which targets the EKGPDPLQ↓ neo-epitope, an elongated version of the CTX-II neo-epitope (EKGPDP↓), speculated to be a blood-precursor of CTX-II generated by the cysteine protease cathepsin K. Human osteoclast cartilage resorption cultures as well as oncostatin M and tumour necr

Nirogacestat suppresses RANKL-Induced osteoclast formation in vitro and attenuates LPS-Induced bone resorption in vivo.

Bone resorption, initiated by osteoclasts (OCs), plays an essential role in bone homeostasis. The abnormalities of bone resorption may induce a series of diseases, including osteoarthritis, osteoporosis and aseptic peri-implant loosening. Nirogacestat (PF-03084014, PF), a novel gamma-secretase inhibitor, has been used in phase II clinical trial for treatment of desmoid tumor. However, whether it has the therapeutic effect on abnormal bone resorption remains to be evaluated. In this study, we investigated the role of PF in the regulation of receptor activator of nuclear factor-kB ligand (RANKL)…

Dehydrocostus lactone attenuates osteoclastogenesis and osteoclast-induced bone loss by modulating NF-κB signalling pathway.

Osteolysis is characterized by overactivated osteoclast formation and potent bone resorption. It is enhanced in many osteoclast-related diseases including osteoporosis and periprosthetic osteolysis. The shortage of effective treatments for these pathological processes emphasizes the importance of screening and identifying potential regimens that could attenuate the formation and function of osteoclasts. Dehydrocostus lactone (DHE) is a natural sesquiterpene lactone containing anti-inflammatory properties. Here, we showed that DHE suppressed receptor activator of nuclear factor-κB ligand (RANKL…

Benzydamine inhibits osteoclast differentiation and bone resorption via down-regulation of interleukin-1 β expression.

Bone diseases such as osteoporosis and periodontitis are induced by excessive osteoclastic activity, which is closely associated with inflam … last formation and bone resorption when added to bone marrow-derived macrophages and differentiated osteoclasts, and the inhibitory effect was reversed by IL-1β treatment. The reporter assay and the inhibitor study of IL-1β transcription suggested that BA inhibited nuclear factor-κB and activator protein-1 by regulating IκB kinase, extracellular signal regula …

What Are the Peripheral Blood Determinants for Increased Osteoclast Formation in the Various Inflammatory Diseases Associated With Bone Loss?

Local priming of osteoclast precursors (OCp) has long been considered the main and obvious pathway that takes place in the human body, where local bone lining cells and RANKL-expressing osteocytes may facilitate the differentiation of OCp. However, priming of OCp away from bone, such as in inflammatory tissues, as revealed in peripheral blood, may represent a second pathway, particularly relevant in individuals who suffer from systemic bone loss such as prevalent in inflammatory diseases. In this review, we used a systematic approach to review the literature on osteoclast formation in peripher

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… Autologous T-cells added to these osteoclasts, prolonged survival of osteoclasts ( 11 ). … Finally, it has been reported for myeloma derived osteoclasts that autologous T-cells added to osteoclast cultures may prolong osteoclast survival ( 11 ). …

Osteoclast-like giant cell tumor of the pancreas-an unusual presentation in a patient with large mantle cell lymphoma.

Osteoclast-like giant cell tumor of the pancreas is very rare. We report a 78-year-old male who was previously treated for large mantle cell lymphoma, was found to have an increased uptake in a peri-pancreatic node from his restaging PET scan. Endoscopic ultrasound-directed fine-needle aspiration of the mass and lymph node revealed an undifferentiated carcinoma with osteoclast-like giant cells. Osteoclast-like giant cell tumors of the pancreas are frequently found to be unresectable at diagnosis due to their large size (>5 cm). In our patient, due to its small size (<3 cm) sub-total pancreatec

The Effect of Combination Spirulina-chitosan on Angiogenesis, Osteoclast, and Osteoblast Cells in Socket Models of Hyperglycemic Rattus norvegicus.

BACKGROUND: Prolongation of the inflammatory process in hyperglycemic interferes with bone formation, inhibits the healing process, and trig … e was a significant increment in the number of capillary lumen, osteoblast cells, and a decrease in osteoclasts in all three treated groups (P1, P2, and P3). CONCLUSIONS: A combination of spirulina and chitosan can effectively promote the healing process in postextraction sockets of type 1 DM R. norvegicus.

Tectorigenin Promotes Osteoblast Differentiation and in vivo Bone Healing, but Suppresses Osteoclast Differentiation and in vivo Bone Resorption.

Although tectorigenin (TG), a major compound in the rhizome of Belamcanda chinensis, is conventionally used for the treatment of inflammatory diseases, its effects on osteogenesis and osteoclastogenesis have not been reported. The objective of this study was to investigate the effects and possible underlying mechanism of TG on in vitro osteoblastic differentiation and in vivo bone formation, as well as in vitro osteoclast differentiation and in vivo bone resorption. TG promoted the osteogenic differentiation of primary osteoblasts and periodontal ligament cells. Moreover, TG upregulated the ex

Ostm1 Bifunctional Roles in Osteoclast Maturation: Insights From a Mouse Model Mimicking a Human OSTM1 Mutation.

Ostm1 mutations are responsible for the most severe form of osteopetrosis in human and mice. To gain insight into Ostm1 cellular functions, … osteoclast deficiency is solely responsible for the mouse phenotype. Our analysis showed oversized osteoclasts with enhanced multinucleation associated with stimulation of intracellular calcium levels, of Nfatc1 nuclear re-localization, and of specific downstream Nfatc1 target genes, providing compelling evidence that Ostm1 is a negative regulator of preoste …

Metaplastic ossification of the temporal artery with osteoclast-like giant cells: a mimicker of giant cell (temporal) arteritis.

PURPOSE: To describe a patient presenting with suspected giant cell (temporal) arteritis (GCA) in whom subsequent temporal artery biopsy sho … the tunica media of the affected artery contained multinucleate giant cells, but these represented osteoclasts and foreign body giant cells reacting to calcium, rather than a part of GCA. RESULTS: This is a rare report of metaplastic ossification and the finding of non-GCA-related giant cells in the tunica media of the temporal artery, thus representing a c …

Hypericin targets osteoclast and prevents breast cancer-induced bone metastasis via NFATc1 signaling pathway.

Bone is the most common target organ of metastasis of breast cancers. This produces considerable morbidity due to skeletal-related events, and severely reduces the quality of life. Increased osteoclast activity is implicated in breast cancer outgrowth in the bone microenvironment. Our previous observation of an anti-osteoclastic activity of hypericin, a natural plant compound, led us to investigate whether hypericin could inhibit bone metastasis and osteolysis caused by breast cancer. We find that hypericin inhibited the upregulation of osteoclasts stimulated by breast cancer cells. The activi…

A vitronectin-derived peptide reverses ovariectomy-induced bone loss via regulation of osteoblast and osteoclast differentiation.

Osteoporosis affects millions of people worldwide by promoting bone resorption and impairing bone formation. Bisphosphonates, commonly used … resorptive function. Moreover, VnP-16 decreased the bone resorbing activity of pre-existing mature osteoclasts without changing their survival rate. Furthermore, VnP-16 had a strong anabolic effect on bone regeneration by stimulating osteoblast differentiation and increasing osteoblast number, and significantly alleviated proinflammatory cytokine-induced bon …

Disturbed MEK/ERK signaling increases osteoclast activity via the Hedgehog-Gli pathway in postmenopausal osteoporosis.

Postmenopausal osteoporosis is a worldwide health problem and is characterized by increased and activated osteoclasts. However, the mechanism by which osteoclasts are dysregulated in postmenopausal osteoporosis is not fully understood. In this study, we found that the Hedgehog-Gli pathway was upregulated in postmenopausal osteoporotic osteoclasts and that 17β-estradiol both inhibited osteoclastogenesis and induced osteoclast apoptosis by downregulating Hedgehog-Gli signaling. Furthermore, we demonstrated that the Hedgehog-Gli pathway was negatively regulated by MEK/ERK signaling and that this …

Pharmacological inhibition of Dock5 prevents osteolysis by affecting osteoclast podosome organization while preserving bone formation.

Osteoporosis is caused by excessive activity of bone-degrading osteoclasts over bone-forming osteoblast. Standard antiosteolytic treatments inhibit bone resorption by inducing osteoclast loss, with the adverse effect of hindering also bone formation. Formation of the osteoclast sealing zone requires Dock5, a guanine nucleotide exchange factor for the small GTPase Rac, and C21, a chemical inhibitor of Dock5, decreases bone resorption by cultured osteoclasts. Here we show that C21 directly inhibits the exchange activity of Dock5 and disrupts osteoclast podosome organization. Remarkably, C21 admi…