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SOST gene suppression stimulates osteocyte Wnt/β-catenin signaling to prevent bone resorption and attenuates particle-induced osteolysis.

The most common cause for prosthetic revision surgery is wear particle-induced periprosthetic osteolysis, which leads to aseptic loosening of the prosthesis. Both SOST gene and its synthetic protein, sclerostin, are hallmarks of osteocytes. According to our previous findings, blocking SOST induces bone formation and protects against bone loss and deformation caused by titanium (Ti) particles by activating the Wnt/β-catenin cascade. Although SOST has been shown to influence osteoblasts, its ability to control wear-particle-induced osteolysis via targeting osteoclasts remains unclear. Mice were …

IL-34 exacerbates pathogenic features of Alzheimer's disease and calvaria osteolysis in triple transgenic (3x-Tg) female mice.

Hallmark features of Alzheimer's disease (AD) include elevated accumulation of aggregated Aβ40 and Aβ42 peptides, hyperphosphorylated Tau (p-Tau), and neuroinflammation. Emerging evidence indicated that interleukin-34 (IL-34) contributes to AD and inflammatory osteolysis via the colony-stimulating factor-1 receptor (CSF-1r). In addition, CSF-1r is also activated by macrophage colony-stimulating factor-1 (M-CSF). While the role of M-CSF in bone physiology and pathology is well addressed, it remains controversial whether IL-34-mediated signaling promotes osteolysis, neurodegeneration, and neuroi…

PLGA nanoparticles engineering extracellular vesicles from human umbilical cord mesenchymal stem cells ameliorates polyethylene particles induced periprosthetic osteolysis.

The wear particle-induced dissolution of bone around implants is a significant pathological factor in aseptic loosening, and controlling prosthetic aseptic loosening holds crucial social significance. While human umbilical cord mesenchymal stem cell-derived exosomes (HucMSCs-Exos, Exos) have been found to effectively promote osteogenesis and angiogenesis, their role in periprosthetic osteolysis remains unexplored. To enhance their in vivo application, we engineered HucMSCs-Exos-encapsulated poly lactic-co-glycolic acid (PLGA) nanoparticles (PLGA-Exos). In our study, we demonstrate that PLGA-Ex…

The ketone body β-hydroxybutyrate alleviates CoCrMo alloy particles induced osteolysis by regulating NLRP3 inflammasome and osteoclast differentiation.

BACKGROUND: Aseptic Loosening (AL) following periprosthetic osteolysis is the main long-term complication after total joint arthroplasty (TJA). However, there is rare effective treatment except for revision surgery, which is costly and painful to the patients. In recent years, the ketone body β-hydroxybutyrate (BHB) has attracted much attention and has been proved to be beneficial in many chronic diseases. With respect to the studies on the ketone body β-hydroxybutyrate (BHB), its anti-inflammatory ability has been widely investigated. Although the ketone body β-hydroxybutyrate has been applie…

Circular RNA CircSLC8A1 contributes to osteogenic differentiation in hBMSCs via CircSLC8A1/miR-144-3p/RUNX1 in periprosthetic osteolysis.

Circular RNAs (circRNAs) are often found in eukaryocyte and have a role in the pathogenesis of a variety of human disorders. Our related research has shown the differential expression of circRNAs in periprosthetic osteolysis (PPOL). However, the involvement of circRNAs in the exact process is yet unknown. CircSLC8A1 expression was evaluated in clinical samples and human bone marrow mesenchymal stem cells (hBMSCs) in this investigation using quantitative real-time PCR. In vitro and in vivo studies were conducted to explicate its functional role and pathway. We demonstrated CircSLC8A1 is involve…

Suppression of NF-κB-induced chronic inflammation mitigates inflammatory osteolysis in the murine continuous polyethylene particle infusion model.

Wear particle-associated bone loss (periprosthetic osteolysis) constrains the longevity of total joint arthroplasty (TJA). Wear particles induce a prolonged upregulation of nuclear factor kappa B (NF-κB) signaling in macrophages and osteoclasts. Synthetic double-stranded oligodeoxynucleotides (ODNs) can prevent the binding of NF-κB to the promoter regions of targeted genes and inhibit genetic activation. We tested the hypothesis that polyethylene-particle induced chronic inflammatory bone loss could be suppressed by local delivery of NF-κB decoy ODNs in murine in vivo model. Polyethylene parti…

Low Rate of Peri-implant Osteolysis in Trabecular Metal Total Ankle Replacement on Short- to Midterm Follow-up.

BACKGROUND: Peri-implant osteolysis is one of the major complications related to total ankle replacement. The aim of this study was to investigate the short- to midterm incidence of peri-implant osteolysis using computed tomography (CT) as imaging method for the Trabecular Metal Total Ankle (TMTA) implant representing a novel total ankle replacement (TAR) implant design regarding material and surgical technique. METHODS: In total, 104 consecutive patients who had a primary TMTA replacement between March 2013 and October 2017 were included in the study. The radiographic evaluation included wei…

Irisin recouples osteogenesis and osteoclastogenesis to protect wear-particle-induced osteolysis by suppressing oxidative stress and RANKL production.

The disruption of bone homeostasis with the decrease in osteoblastic bone formation and facilitated osteoclastic bone resorption is the leading cause of periprosthetic osteolysis. Accumulative studies have indicated that irisin has the function of maintaining and rebalancing bone homeostasis. In this study, we explored the protective effect of irisin on wear-particle-induced osteolysis in mice. The results showed that irisin effectively inhibited titanium (Ti) particle-induced calvarial osteolysis, supported by a lower bone loss and existence of more collagen, compared with the ones stressed b…

IL-17A-Mediated Immune-Inflammatory Periarticular Mass and Osteolysis From Impingement in Ceramic-On-Ceramic Total Hip Arthroplasty.

We present a rare case of symptomatic adverse local tissue reaction in a 54-year-old female patient who had undergone total hip arthroplasty with ceramic-on-ceramic bearing. Inflammatory periarticular mass and osteolysis developed in the absence of cobalt chrome alloy interfaces and a modular neck component. On the pathologic images, there was no clear evidence of gross metal staining of tissues, metal corrosion, and ceramic or metal wear particles. However, there were impingement scars on the titanium alloy femoral neck and acetabular cup associated with a high combined anteversion angle of 7…

Osteolysis in total hip arthroplasty in relation to metal ion release: Comparison between monolithic prostheses and different modularities.

BACKGROUND: Among the various complications associated with total hip arthroplasty (THA) periprosthetic osteolysis and wear phenomena due to the release of metal particles, are two of the most common and have been reported to be correlated because of inflammatory responses directed towards released particles that generally activate macrophagic osteolytic effects. Therein, new masses known as pseudotumors can appear in soft tissues around a prosthetic implant. To date, there is paucity of reliable data from studies investigating for any association between the above mentioned adverse events. A…

Protocatechualdehyde inhibits receptor activator of nuclear factor kappa-B ligand-induced osteoclastogenesis and attenuates lipopolysaccharide-induced inflammatory osteolysis.

Inflammatory osteolysis as a consequence of chronic bacterial infection underlies several lytic bone conditions, such as otitis media, osteomyelitis, septic arthritis, periodontitis, periprosthetic infection, and aseptic loosening of orthopedic implants. In consideration of the lack of effective preventive or treatments options against infectious osteolysis, the exploitation of novel pharmacological compounds/agents is critically required. The present study assessed the effect of protocatechualdehyde (PCA), a natural occurring polyphenolic compound with diverse biological activities including …

MgO Nanoparticles Protect against Titanium Particle-Induced Osteolysis in a Mouse Model Because of Their Positive Immunomodulatory Effect.

Aseptic prosthetic loosening (APL) often leads to the failure of prostheses. It is inseparable from wear-particle-induced macrophage-mediated inflammatory responses and osteolysis. Mg2+ is a metal ion with excellent anti-inflammatory properties. Herein, Mg2+ was introduced into a nanomedicine (MgO nanoparticles (MNPs)) to protect against APL. MNPs could be phagocytized by macrophages and gradually degraded intracellularly. Following MNPs treatment, lipopolysaccharide (LPS)-activated macrophages polarized into deeper M1 phenotype at 6 h but then switched to the M2 phenotype at 48 h. Furthermore…

Retraction of: A005, a novel inhibitor of phosphatidylinositol 3-kinase/mammalian target of rapamycin, prevents osteosarcoma-induced osteolysis.

Osteosarcoma is the most frequent primary bone tumor in children and adolescents. The phosphatidylinositol 3-kinase (PI3K)/mammalian target … one resorption in vitro. Therefore, A005 was further applied to a SaOS-2 osteosarcoma-induced mouse osteolysis model. A005 inhibited tumor growth and prevented osteosarcoma-associated osteolysis via modulation of the PI3K/AKT/mTOR pathway. Overall, our results showed that A005 inhibited osteoclastogenesis and prevented osteosarcoma-induced bone osteolysis by …

IL-11 is essential in promoting osteolysis in breast cancer bone metastasis via RANKL-independent activation of osteoclastogenesis.

A variety of osteolytic factors have been identified from breast cancer cells leading to osteolysis, but less is known about which factor plays an essential role in the initiation process prior to the overt vicious osteolytic cycle. Here, we present in vitro and in vivo evidences to clarify the role of interleukin-11 (IL-11) as an essential contributor to breast cancer bone metastasis mediated osteolysis. Animal studies showed that bone specific metastatic BoM-1833 cells induce earlier onset of osteolysis and faster tumor growth compared with MCF7 and parental MDA-MB-231 cells in BALB/c-nu/nu …

Cepharanthine ameliorates titanium particle-induced osteolysis by inhibiting osteoclastogenesis and modulating OPG/RANKL ratio in a murine model.

Periprosthetic asepteic loosening, caused by wear debris, is one of the most severe complications, generally resulting in implant failure. Extensive osteoclast formation and activation are considered as the cause for periprosthetic osteolysis. However, few approaches have been approved to be used for preventing early-stage periprosthetic osteolysis. In this study, we investigated the preventive effects of CEP on titanium particles-induced osteolysis in a murine calvaria model. This inhibitory effect was confirmed to be realized by attenuating osteoclastogenesis in vivo. In addition, CEP marked…

Abietic acid attenuates RANKL induced osteoclastogenesis and inflammation associated osteolysis by inhibiting the NF-KB and MAPK signaling.

Osteoporosis is a major debilitating cause of fractures and decreases the quality of life in elderly patients. Bone homeostasis is maintained by bone forming osteoblasts and bone resorpting osteoclasts. Substantial evidences have shown that targeting osteoclasts using natural products is a promising strategy for the treatment of osteoporosis. In the current study, we investigated the osteoprotective effect of Abietic acid (AA) in in vitro and in vivo models of osteolysis. In vitro experiments demonstrated that, AA suppressed receptor activator of nuclear factor-kappa B ligand (RANKL)-induced o…

NS-018 reduces myeloma cell proliferation and suppresses osteolysis through inhibition of the JAK2 and Src signaling pathways.

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… Fig. 2 NS-018 inhibits RANKL-induced osteoclast formation and suppresses osteolysis in mice with intratibial transplantation of RPMI 8226 cells. … Heusschen and Muller 12 found that the Src inhibitor saracatinib limits the development of osteolysis in a murine osteolytic model induced by murine myeloma cells. …

Stevioside Prevents Wear Particle-Induced Osteolysis by Inhibiting Osteoclastogenesis and Inflammatory Response via the Suppression of TAK1 Activation.

Aseptic loosening and periprosthetic osteolysis are the leading causes of total joint arthroplasty failure, which occurs as a result of chronic inflammatory response and enhanced osteoclast activity. Here we showed that stevioside, a natural compound isolated from Stevia rebaudiana, exhibited preventative effects on titanium particle-induced osteolysis in a mouse calvarial model. Further histological assessment and real-time PCR analysis indicated that stevioside prevented titanium particle-induced osteolysis by inhibiting osteoclast formation and inflammatory cytokine expression in vivo. In v…

Endoplasmic reticulum stress-mediated inflammatory signaling pathways within the osteolytic periosteum and interface membrane in particle-induced osteolysis.

Aseptic loosening secondary to periprosthetic inflammatory osteolysis results from the biological response to wear particles and is a leading cause of arthroplasty failure. The origin of this inflammatory response remains unclear. We aim to validate the definite link between endoplasmic reticulum (ER) stress and particle-induced inflammatory signaling pathways in periprosthetic osteolysis. We examine the histopathologic changes of osteolysis and the expression of specific biomarkers for ER-stress-mediated inflammatory signaling pathways (IRE1α, GRP78/Bip, c-Fos, NF-κB, ROS and Ca(2+)). Moreove…

Metallosis, complete osteolysis of ilium, acetabulum and proximal femur. Disastrous complication of total hip arthoplasty: A case report.

Metallosis is serious condition that comes about when metallic debris builds up in the soft tissues of the body. This condition is seen in individuals undergoing joint replacement surgery, like those of the hip, knee and elbow. Incidence of metallosis is not common. Here we present a case of 61 year-old male, who had undergone right-sided total hip replacement 20 years earlier due to avascular necrosis. He presented to us with one-year history of massive swelling of right thigh and mild pain and discomfort in September 2013. He was unable to carry weight on the affected limb and had been bed-r