In vitro
            and
            in vivo
            biological responses to a novel radiopacifying agent for bone cement

Iodixanol (IDX) and iohexol (IHX) have been investigated as possible radiopacification agents for polymethylmethacrylate (PMMA) bone cement, to replace the currently used barium sulphate and zirconia. IDX and IHX are both water-soluble iodine-based contrast media and for the last 20 years have been used extensively in clinical diagnostic procedures such as contrast media enhanced computed tomography, angiography and urography. One of the major reasons to remove the current radiopacifying agents is their well-documented cytotoxicity and their potential to increase bone resorption. Using in vitro bone resorption assays, the effect of PMMA particles plus IDX or IHX to induce osteoclast formation and lacunar resorption on dentine slices has been investigated. These responses have been compared with the in vitro response to PMMA particles containing the conventional radiopacifying agents, that is, barium sulphate and zirconia. In parallel, the in vivo reaction, in terms of new bone formation, to particles of these materials has been tested using a bone harvest chamber in rabbit tibiae. In vitro cell culture showed that PMMA containing IHX resulted in significantly less bone resorption than PMMA containing the conventional opacifiers. In vivo testing, however, showed no significant differences between the amounts of new bone formed around cement samples containing the two iodine-based opacifying agents in particulate form, although both led to fewer inflammatory cells than particles of PMMA containing zirconia. Our results suggest that a non-ionic radiopacifier could be considered as an alternative to the conventional radiopacifying agents used in biomaterials in orthopaedic surgery.

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Biological Effects of β-Glucans on Osteoclastogenesis

Molecules ◽

10.3390/molecules26071982 ◽

2021 ◽

Vol 26 (7) ◽

pp. 1982

Author(s):

Wataru Ariyoshi ◽

Shiika Hara ◽

Ayaka Koga ◽

Yoshie Nagai-Yoshioka ◽

Ryota Yamasaki

Keyword(s):

Bone Resorption ◽

Bone Marrow Cells ◽

Biological Effects ◽

Osteoclast Differentiation ◽

Treatment Strategies ◽

Alcaligenes Faecalis ◽

Osteoclast Formation ◽

Osteoclast Precursors

Although the anti-tumor and anti-infective properties of β-glucans have been well-discussed, their role in bone metabolism has not been reviewed so far. This review discusses the biological effects of β-glucans on bone metabolisms, especially on bone-resorbing osteoclasts, which are differentiated from hematopoietic precursors. Multiple immunoreceptors that can recognize β-glucans were reported to be expressed in osteoclast precursors. Coordinated co-stimulatory signals mediated by these immunoreceptors are important for the regulation of osteoclastogenesis and bone remodeling. Curdlan from the bacterium Alcaligenes faecalis negatively regulates osteoclast differentiation in vitro by affecting both the osteoclast precursors and osteoclast-supporting cells. We also showed that laminarin, lichenan, and glucan from baker’s yeast, as well as β-1,3-glucan from Euglema gracilisas, inhibit the osteoclast formation in bone marrow cells. Consistent with these findings, systemic and local administration of β-glucan derived from Aureobasidium pullulans and Saccharomyces cerevisiae suppressed bone resorption in vivo. However, zymosan derived from S. cerevisiae stimulated the bone resorption activity and is widely used to induce arthritis in animal models. Additional research concerning the relationship between the molecular structure of β-glucan and its effect on osteoclastic bone resorption will be beneficial for the development of novel treatment strategies for bone-related diseases.

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Development of Novel Bioactive PMMA-Based Bone Cement and its In Vitro and In Vivo Evaluation

Key Engineering Materials ◽

10.4028/www.scientific.net/kem.309-311.801 ◽

2006 ◽

Vol 309-311 ◽

pp. 801-804 ◽

Cited By ~ 3

Author(s):

S.B. Cho ◽

Akari Takeuchi ◽

Ill Yong Kim ◽

Sang Bae Kim ◽

Chikara Ohtsuki ◽

...

Keyword(s):

Mechanical Property ◽

Compressive Strength ◽

Bone Cement ◽

The Novel ◽

In Vivo Evaluation ◽

Natural Bone ◽

Pmma Bone Cement ◽

Rabbit Tibia

In order to overcome the disadvantage of commercialized PMMA bone cement, we have developed novel PMMA-based bone cement(7P3S) reinforced by 30 wt.% of bioactive CaO-SiO2 gel powders to induce the bioactivity as well as to increase mechanical property for the PMMA bone cement. The novel 7P3S bone cement hardened after mixing for about 7 minutes. For in vitro evaluation, apatite forming ability of it was investigated using SBF. When the novel 7P3S bone cement was soaked into SBF, it formed apatite on its surfaces within 1 week Furthermore; there is no decrease in its compressive strength within 9 weeks soaking in SBF. It is though that hardly decrease in compressive strength of 7P3S bone cement in SBF is due to the relative small amount of gel powder or its spherical shape and monosize. In vivo evaluation of the novel 7P3S bone cement was carried out using rabbit. After implantion into rabbit tibia for several periods, the interface between novel bone cement and natural bone was evaluated by CT images. According to the results, the novel bone cement directly contact to the natural bone without fibrous tissue after implantation for 4 weeks. This results indicates that the newly developed 7P3S bone cement can bond to the living bone and also be effectively used as bioactive bone cement without decrease in mechanical property.

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

Experimental Cell Research ◽

10.1016/j.yexcr.2019.06.015 ◽

2019 ◽

Vol 382 (1) ◽

pp. 111470 ◽

Cited By ~ 4

Author(s):

Xuzhuo Chen ◽

Xinwei Chen ◽

Zhihang Zhou ◽

Yi Mao ◽

Yexin Wang ◽

...

Keyword(s):

Bone Resorption ◽

Osteoclast Formation

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Dihydroartemisinin prevents breast cancer-induced osteolysis via inhibiting both breast caner cells and osteoclasts

Scientific Reports ◽

10.1038/srep19074 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 20

Author(s):

Ming-Xuan Feng ◽

Jian-Xin Hong ◽

Qiang Wang ◽

Yong-Yong Fan ◽

Chi-Ting Yuan ◽

...

Keyword(s):

Breast Cancer ◽

Bone Resorption ◽

Molecular Mechanisms ◽

Osteoclast Differentiation ◽

Metastatic Breast ◽

Osteoclast Formation ◽

Migration And Invasion ◽

Titanium Particle

Abstract Bone is the most common site of distant relapse in breast cancer, leading to severe complications which dramatically affect the patients’ quality of life. It is believed that the crosstalk between metastatic breast cancer cells and osteoclasts is critical for breast cancer-induced osteolysis. In this study, the effects of dihydroartemisinin (DHA) on osteoclast formation, bone resorption, osteoblast differentiation and mineralization were initially assessed in vitro, followed by further investigation in a titanium-particle-induced osteolysis model in vivo. Based on the proved inhibitory effect of DHA on osteolysis, DHA was further applied to MDA-MB-231 breast cancer-induced mouse osteolysis model, with the underlying molecular mechanisms further investigated. Here, we verified for the first time that DHA suppressed osteoclast differentiation, F-actin ring formation and bone resorption through suppressing AKT/SRC pathways, leading to the preventive effect of DHA on titanium-particle-induced osteolysis without affecting osteoblast function. More importantly, we demonstrated that DHA inhibited breast tumor-induced osteolysis through inhibiting the proliferation, migration and invasion of MDA-MB-231 cells via modulating AKT signaling pathway. In conclusion, DHA effectively inhibited osteoclastogenesis and prevented breast cancer-induced osteolysis.

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Inhibition of lipopolysacharide induced osteoclast formation and bone resorption in vitro and in vivo in mice by cystatin C

Bone Abstracts ◽

10.1530/boneabs.1.pp225 ◽

2013 ◽

Author(s):

Stralberg Fredrik ◽

Catharina Lindholm ◽

Erik Lindstrom ◽

Franciszek Kasprzykowski ◽

Paul Saftig ◽

...

Keyword(s):

Bone Resorption ◽

Cystatin C ◽

Osteoclast Formation

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In Vitro and In Vivo Evaluation of Vancomycin-Loaded PMMA Cement in Combination with Ultrasound and Microbubbles-Mediated Ultrasound

BioMed Research International ◽

10.1155/2015/309739 ◽

2015 ◽

Vol 2015 ◽

pp. 1-7 ◽

Cited By ~ 8

Author(s):

Tiao Lin ◽

Xun-Zi Cai ◽

Ming-Min Shi ◽

Zhi-Min Ying ◽

Bin Hu ◽

...

Keyword(s):

Bone Cement ◽

Joint Infection ◽

Study Groups ◽

In Vivo Evaluation ◽

Pmma Bone Cement ◽

Prosthetic Joint ◽

New Zealand White Rabbits ◽

Pmma Cement

Ultrasound (US) has been used to increase elution of antibiotic from an antibiotic-loaded poly(methyl methacrylate) (PMMA) bone cement (ALBC). We aimed to further investigate whether microbubbles-mediated US (US + MB) facilitate elution of vancomycin (VAN) from cylindrical specimens and enhance the activity of the eluted antibiotic againstStaphylococcus aureus(S. aureus) in vitro. The study groups comprised cylindrical bone cement fabricated with VAN (VAN), ALBC using US (VAN + US), and ALBC using MB-mediated US (VAN + US + MB). We also carried out an in vivo study involving the activity of VAN from cylindrical cement implanted in tibiae of New Zealand white rabbits inoculated withS. aureus. We found that (1) in vitro, elution from VAN + US + MB cylinders was significantly higher than from either the VAN or VAN + US specimens; (2) the activity of the eluted VAN from the VAN + US + MB cylinders against planktonicS. aureuswas significantly higher than from either the control or VAN or VAN + US specimens; and (3) in the rabbits, the activity of the eluted VAN from the VAN + US + MB cylinders againstS. aureuswas significantly higher than from either the control or VAN or VAN + US specimens. The present results suggest that VAN-loaded PMMA cement irradiated with MB-mediated US may have a role in controlling prosthetic joint infection.

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Successful Clinical Use of Daptomycin-Impregnated Bone Cement in Two-Stage Revision Hip Surgery for Prosthetic Joint Infection

Annals of Pharmacotherapy ◽

10.1345/aph.1r486 ◽

2013 ◽

Vol 47 (1) ◽

pp. e2-e2 ◽

Cited By ~ 13

Author(s):

Nicholas J Cortes ◽

John M Lloyd ◽

Leszek Koziol ◽

Lawrence O'Hara

Keyword(s):

Bone Cement ◽

Prosthetic Joint Infection ◽

Revision Surgery ◽

Past History ◽

Joint Infection ◽

Pmma Bone Cement ◽

Prosthetic Joint ◽

History Of

OBJECTIVE To describe the safe and successful use of daptomycin-impregnated polymethyl methacrylate (PMMA) bone cement in the treatment of a case of recurrent prosthetic joint infection in a patient with multiple antibiotic allergies and past colonization with multiply antibiotic-resistant organisms. CASE SUMMARY A 79-year-old female had a history of chronic recurrent left prosthetic hip infection. The patient had confirmed allergies to multiple antibiotics and a past history of colonization with methicillin-resistant Staphylococcus aureus. At first-stage revision surgery, the infected prosthesis was removed and samples were sent for microbiologic culture. A spacer device was fashioned, with incorporation of daptomycin and gentamicin into the PMMA bone cement at a concentration of 5% w/w for each antibiotic. Systemic daptomycin and gentamicin were administered postoperatively for 14 days. Propionibacterium acnes was isolated from deep-tissue specimens. The patient made excellent postoperative progress and was discharged after 2 weeks. Second-stage revision surgery was performed at 6 months, with no signs of persistent infection. She remained well, pain free, and mobilizing independently 2 years later. DISCUSSION Daptomycin, a cyclic lipopeptide antibiotic, is approved for systemic treatment of endocarditis and skin and soft tissue infections. In vitro data demonstrate acceptable drug elution from and tensile strength of daptomycin-impregnated PMMA bone cement; however, clinical data are lacking. In our patient's case, the cement formulation was well tolerated, with no adverse effects detected, and demonstrated adequate mechanical strength in vivo. Infection with P. acnes, an unusual pathogen, was successfully treated. Further clinical studies are required to assess the efficacy of daptomycin-impregnated cement in infection with more typical pathogens, such as S. aureus. CONCLUSIONS Daptomycin impregnation of PMMA bone cement may be an option in cases in which patient or pathogen factors preclude use of routinely incorporated agents.

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LY900009 Regulates RANKL-Induced Osteoclast Formation and LPS-Induced Bone Resorption

10.21203/rs.3.rs-132552/v1 ◽

2020 ◽

Author(s):

Tao Huang ◽

Congyun Zhao ◽

Yi Zhao ◽

Yuan Zhou ◽

Lei Wang ◽

...

Keyword(s):

Bone Resorption ◽

Suppressive Effect ◽

Inhibitory Effect ◽

Osteoclast Formation ◽

Dependent Manner ◽

In Vivo Experiments ◽

Secretase Inhibitor ◽

Formation Number

Abstract To investigate the suppressive function of LY900009, a potent-secretase inhibitor, on RANKL-induced osteoclastogenesis. The cytotoxicity of LY900009 was evaluated. The suppressive effect and possible molecular mechanism of LY900009 on RANKL-induced osteoclastogenesis was evaluated both in vitro and in vivo. The IC50 of LY900009 was 2.93 mM. LY900009 treatment at different doses (100 nM, 200 nM, and 400 nM) effectively reduced osteoclast formation (number and arear) in a dose-dependent manner. The qPCR result shows that LY900009 attenuates RANKL-induced osteoclast formation and NFATc1 protein expression. The in vivo experiments demonstrated the inhibitory effect of LY900009 on LPS-induced bone resorption. LY900009 could potently inhibit osteoclastogenesis and bone resorption by down-regulating Notch/MAPK/Akt - mediated NFATc1 reduction in vitro. In accordance with the in vitro observations, we confirmed that LY900009 attenuated LPS-induced osteolysis in mice. In conclusion, our findings indicate that Notch was a potential therapeutic target which could be used for osteolytic diseases treatment.

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IL-33 Inhibits TNF-α-Induced Osteoclastogenesis and Bone Resorption

International Journal of Molecular Sciences ◽

10.3390/ijms21031130 ◽

2020 ◽

Vol 21 (3) ◽

pp. 1130 ◽

Cited By ~ 8

Author(s):

Fumitoshi Ohori ◽

Hideki Kitaura ◽

Saika Ogawa ◽

Wei-Ren Shen ◽

Jiawei Qi ◽

...

Keyword(s):

Bone Resorption ◽

Nuclear Translocation ◽

Bone Marrow Cells ◽

Bone Destruction ◽

Osteoclast Formation ◽

Tartrate Resistant Acid Phosphatase ◽

Ct Reconstruction ◽

Tnf Α

Interleukin (IL)-33 is a member of the IL-1 family, which acts as an alarmin. Several studies suggested that IL-33 inhibited osteoclastogenesis and bone resorption. Tumor necrosis factor-α (TNF-α) is considered a direct inducer of osteoclastogenesis. However, there has been no report regarding the effect of IL-33 on TNF-α-induced osteoclastogenesis and bone resorption. The objective of this study is to investigate the role of IL-33 on TNF-α-induced osteoclastogenesis and bone resorption. In an in vitro analysis of osteoclastogenesis, osteoclast precursors, which were derived from bone marrow cells, were treated with or without IL-33 in the presence of TNF-α. Tartrate-resistant acid phosphatase (TRAP) staining solution was used to assess osteoclast formation. In an in vivo analysis of mouse calvariae, TNF-α with or without IL-33 was subcutaneously administrated into the supracalvarial region of mice daily for 5 days. Histological sections were stained for TRAP, and osteoclast numbers were determined. Using micro-CT reconstruction images, the ratio of bone destruction area on the calvariae was evaluated. The number of TRAP-positive cells induced by TNF-α was significantly decreased with IL-33 in vitro and in vivo. Bone resorption was also reduced. IL-33 inhibited IκB phosphorylation and NF-κB nuclear translocation. These results suggest that IL-33 inhibited TNF-α-induced osteoclastogenesis and bone resorption.

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Bone Resorption Induced by Titanium Implantation Through Activation of Osteoclast Formation via C3a

10.21203/rs.3.rs-66781/v1 ◽

2020 ◽

Author(s):

Xiaohan Liu ◽

Siwen Li ◽

Yuan Meng ◽

Yu Fan ◽

Ce Shi ◽

...

Keyword(s):

Bone Resorption ◽

Inflammatory Responses ◽

Titanium Implant ◽

Osteoclast Formation ◽

Alternative Pathways ◽

Tnf Α ◽

Differentiation And Proliferation ◽

Pro Inflammatory Cytokines

Abstract Titanium implantation is widely used for dental replacement with advantages of excellent mechanical strength, corrosion resistance, chemical stability and biocompatibility. Some patients, however, are subject to the failure of implantation due to bone resorption, which closely related to the inflammatory responses without clear mechanisms. In this study, first we found that there were inflammatory responses and increases of osteoclasts in the surrounding tissues near by the titanium implant. Further, data revealed that the C3 was increased in the serum and surrounding tissues near by the titanium implant, and activated by classical and alternative pathways. Next, we recognized that the C3a/C3aR, no C3b played an important role in stimulating secretions of pro-inflammatory cytokines of TNF-α and MMP9 via transcription factors NF-kB and NFATc1. This cascade of responses to titanium implant leaded the differentiation and proliferation of osteoclasts in vivo and in vitro, bone resorption of surrounding tissues of Ti implant. These suggest that the cleaved C3a fragment plays predominant roles in the activation of osteoclast. Therefore, the blocking C3a activation should provide potential to prevent bone resorption and prolong the survival of biomaterial implants.

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