Suppression Effect of Astaxanthin on Osteoclast Formation In Vitro and Bone Loss In Vivo

Post-operative infections in orthopaedic implants are severe complications that require urgent solutions. Although conventional antibiotics limit bacterial biofilm formation, they ignore the bone loss caused by osteoclast formation during post-operative orthopaedic implant-related infections. Fortunately, enoxacin exerts both antibacterial and osteoclast inhibitory effects, playing a role in limiting infection and preventing bone loss. However, enoxacin lacks specificity in bone tissue and low bioavailability-related adverse effects, which hinders translational practice. Here, we developed a nanosystem (Eno@MSN-D) based on enoxacin (Eno)-loaded mesoporous silica nanoparticles (MSN), decorated with the eight repeating sequences of aspartate (D-Asp8), and coated with polyethylene glycol The release results suggested that Eno@MSN-D exhibits a high sensitivity to acidic environment. Moreover, this Eno@MSN-D delivery nanosystem exhibited both antibacterial and anti-osteoclast properties in vitro. The cytotoxicity assay revealed no cytotoxicity at the low concentration (20 μg/ml) and Eno@MSN-D inhibited RANKL-induced osteoclast differentiation. Importantly, Eno@MSN-D allowed the targeted release of enoxacin in infected bone tissue. Bone morphometric analysis and histopathology assays demonstrated that Eno@MSN-D has antibacterial and antiosteoclastic effects in vivo, thereby preventing implant-related infections and bone loss. Overall, our study highlights the significance of novel biomaterials that offer new alternatives to treat and prevent orthopaedic Staphylococcus aureus-related implantation infections and bone loss.

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GSH attenuates RANKL-induced osteoclast formation in vitro and LPS-induced bone loss in vivo

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2020.110305 ◽

2020 ◽

Vol 128 ◽

pp. 110305 ◽

Cited By ~ 2

Author(s):

Bing Han ◽

Huan Geng ◽

Liang Liu ◽

Zhixin Wu ◽

Yizhong Wang

Keyword(s):

Bone Loss ◽

Osteoclast Formation

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IκB kinase (IKK)β, but not IKKα, is a critical mediator of osteoclast survival and is required for inflammation-induced bone loss

Journal of Experimental Medicine ◽

10.1084/jem.20042081 ◽

2005 ◽

Vol 201 (10) ◽

pp. 1677-1687 ◽

Cited By ~ 193

Author(s):

Maria Grazia Ruocco ◽

Shin Maeda ◽

Jin Mo Park ◽

Toby Lawrence ◽

Li-Chung Hsu ◽

...

Keyword(s):

Bone Loss ◽

Nuclear Factor Κb ◽

Osteoclast Formation ◽

Catalytic Subunits ◽

Iκb Kinase ◽

Induced Apoptosis ◽

Factor Α ◽

Osteoclast Survival

Transcription factor, nuclear factor κB (NF-κB), is required for osteoclast formation in vivo and mice lacking both of the NF-κB p50 and p52 proteins are osteopetrotic. Here we address the relative roles of the two catalytic subunits of the IκB kinase (IKK) complex that mediate NF-κB activation, IKKα and IKKβ, in osteoclast formation and inflammation-induced bone loss. Our findings point out the importance of the IKKβ subunit as a transducer of signals from receptor activator of NF-κB (RANK) to NF-κB. Although IKKα is required for RANK ligand-induced osteoclast formation in vitro, it is not needed in vivo. However, IKKβ is required for osteoclastogenesis in vitro and in vivo. IKKβ also protects osteoclasts and their progenitors from tumor necrosis factor α–induced apoptosis, and its loss in hematopoietic cells prevents inflammation-induced bone loss.

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A Bone-Targeting Enoxacin Delivery System to Eradicate Staphylococcus Aureus-Related Implantation Infections and Bone Loss

10.21203/rs.3.rs-645601/v1 ◽

2021 ◽

Author(s):

Cong Yao ◽

Qiang Xu ◽

Xiuguo Han ◽

Qianyuan Tao ◽

Xuwen Luo ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Bone Loss ◽

Mesoporous Silica Nanoparticles ◽

Osteoclast Formation ◽

Orthopaedic Implant ◽

Inhibitory Effects ◽

Conventional Antibiotics ◽

Targeted Release

Abstract Post-operative infections in orthopaedic implants are severe complications that require urgent solutions. Although conventional antibiotics limit bacterial biofilms formation, they ignore the bone loss caused by osteoclast formation during post-operative orthopaedic implant-related infections. Fortunately, enoxacin exerts dual antibacterial and osteoclast inhibitory effects, playing a pivot in limiting infection and preventing bone loss. However, enoxacin lacks specificity in bone tissue and low bioavailability-relate side effects, which hinders translational practice. Herein, we developed a nanosystem (Eno@MSN-D) based on enoxacin (Eno)-loaded mesoporous silica nanoparticles (MSN), decorated with the eight repeating sequences of aspartate (D-Asp8), and coated with polyethylene glycol (PEG). This Eno@MSN-D delivery nanosystem exhibited both antibacterial and anti-osteoclast properties in vitro. More importantly, Eno@MSN-D allowed the targeted release of enoxacin in infected bone tissues and prevented implant-related infection and bone loss in vivo. Therefore, our work highlights the significance of novel biomaterials that offer new alternatives to treat and prevent orthopaedic staphylococcus aureus-related implantation infections and bone loss.

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Fermented Oyster Extract Prevents Ovariectomy-Induced Bone Loss and Suppresses Osteoclastogenesis

Nutrients ◽

10.3390/nu11061392 ◽

2019 ◽

Vol 11 (6) ◽

pp. 1392 ◽

Cited By ~ 4

Author(s):

Hye Jung Ihn ◽

Ju Ang Kim ◽

Soomin Lim ◽

Sang-Hyeon Nam ◽

So Hyeon Hwang ◽

...

Keyword(s):

Bone Loss ◽

Type I Collagen ◽

Therapeutic Option ◽

Osteoclast Differentiation ◽

Nuclear Factor Κb ◽

Osteoclast Formation ◽

Type I ◽

Bioactive Substances

There is growing interest in bioactive substances from marine organisms for their potential use against diverse human diseases. Osteoporosis is a skeletal disorder associated with bone loss primarily occurring through enhanced osteoclast differentiation and resorption. Recently, we reported the anti-osteoclastogenic activity of fermented Pacific oyster (Crassostrea gigas) extract (FO) in vitro. The present study focused on investigating the anti-osteoporotic efficacy of FO in bone loss prevention in an experimental animal model of osteoporosis and elucidating the mechanism underlying its effects. Oral administration of FO significantly decreased ovariectomy-induced osteoclast formation and prevented bone loss, with reduced serum levels of bone turnover biomarkers including osteocalcin and C-terminal telopeptide fragment of type I collagen C-terminus (CTX). FO significantly suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced differentiation of bone marrow-derived macrophages (BMMs) into osteoclasts and attenuated the induction of osteoclast-specific genes required for osteoclastogenesis and bone resorption. Furthermore, FO inhibited RANKL-mediated IκBα and p65 phosphorylation in BMMs. Taken together, these results demonstrate that FO effectively suppresses osteoclastogenesis in vivo and in vitro, and that FO can be considered as a potential therapeutic option for the treatment of osteoporosis and osteoclast-mediated skeletal diseases.

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Berberine Suppresses RANKL-Induced Osteoclast Differentiation by Inhibiting c-Fos and NFATc1 Expression

The American Journal of Chinese Medicine ◽

10.1142/s0192415x19500228 ◽

2019 ◽

Vol 47 (02) ◽

pp. 439-455 ◽

Cited By ~ 3

Author(s):

Sang-Yong Han ◽

Yun-Kyung Kim

Keyword(s):

Bone Loss ◽

Osteoclast Differentiation ◽

Osteoclast Formation ◽

Bone Diseases ◽

Mrna Levels ◽

Nuclear Factor ◽

Activated T Cells ◽

Murine Bone Marrow

Osteoporosis is a common disorder of bone remodeling, marked by excessive osteoclast formation. Recent studies indicated that berberine (BBR) is a potential natural drug for the treatment of various bone diseases. However, it still needs to be further studied for the treatment of osteoporosis. The current study investigated the inhibitory effects of BBR on receptor activator of nuclear factor-[Formula: see text]B ligand (RANKL)-induced osteoclast differentiation in vitro and in vivo. Cell-based assays were performed using osteoclasts generated in cultures of murine bone marrow-derived macrophages (BMMs) treated with RANKL and M-CSF. The effects of BBR on in vivo lipopolysaccharide (LPS)-mediated bone loss were evaluated using ICR mice. BBR significantly inhibited TRAP-positive osteoclast formation induced by RANKL. BBR also inhibited RANKL-induced Akt, p38 and ERK phosphorylation and I[Formula: see text]B degradation, and suppressed RANKL-induced expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1), which is a key transcription factors for osteoclast formation. BBR reduced the mRNA levels of osteoclast markers, including TRAP, osteoclast-associated receptor (OSCAR), cathepsin K, and ATPase H[Formula: see text] transporting V0 subunit d2 (ATP6v0d2). Moreover, BBR prevented LPS-mediated bone loss in vivo. We suggest BBR as a natural compound that can be a potential therapeutic agent for osteoclast-related bone diseases.

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Small molecule inhibitors of IκB kinase signaling inhibit osteoclast formation in vitro and prevent ovariectomy‐induced bone loss in vivo

The FASEB Journal ◽

10.1096/fj.10-164095 ◽

2010 ◽

Vol 24 (11) ◽

pp. 4545-4555 ◽

Cited By ~ 31

Author(s):

Aymen I. Idris ◽

Maala Krishnan ◽

Petra Simic ◽

Euphemie Landao‐Bassonga ◽

Patrick Mollat ◽

...

Keyword(s):

Bone Loss ◽

Small Molecule ◽

Small Molecule Inhibitors ◽

Osteoclast Formation ◽

Kinase Signaling ◽

Iκb Kinase ◽

Inhibit Osteoclast Formation

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Ethanolic extract of Schizonepeta tenuifolia attenuates osteoclast formation and activation in vitro and protects against lipopolysaccharide-induced bone loss in vivo

BMC Complementary and Alternative Medicine ◽

10.1186/s12906-016-1300-0 ◽

2016 ◽

Vol 16 (1) ◽

Cited By ~ 4

Author(s):

Ju-Young Kim ◽

Jong Min Baek ◽

Sung-Jun Ahn ◽

Yoon-Hee Cheon ◽

Sun-Hyang Park ◽

...

Keyword(s):

Bone Loss ◽

Ethanolic Extract ◽

Osteoclast Formation ◽

Schizonepeta Tenuifolia

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Osteoblast-osteoclast co-culture amplifies inhibitory effects of FG-4592 on osteoclast formation and reduces bone resorption activity

10.1101/863498 ◽

2019 ◽

Author(s):

Philippa A Hulley ◽

Ioanna Papadimitriou-Olivgeri ◽

Helen J Knowles

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Formation ◽

Enzyme Inhibitors ◽

Enzyme Inhibitor ◽

Osteoclast Formation ◽

Potential Contribution ◽

Non Union

AbstractThe 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 stabilise HIF protein, introduces the potential for a new clinical strategy to treat osteolytic conditions such as osteoporosis, osteonecrosis and skeletal fracture and non-union. However, bone-resorbing osteoclasts also play a central role in bone remodelling and pathological osteolysis and HIF promotes osteoclast activation and bone loss in vitro. It is therefore likely that the final outcome of PHD enzyme inhibition in vivo would be mediated by a balance between increased bone formation and increased bone resorption. It is essential that we improve our understanding of the effects of HIF on osteoclast formation and function, and consider the potential contribution of inhibitory interactions with other musculoskeletal cells.The PHD enzyme inhibitor FG-4592 stabilised HIF protein and stimulated osteoclast-mediated bone resorption, but inhibited differentiation of human CD14+ monocytes into osteoclasts. Formation of osteoclasts in a more physiologically relevant 3D collagen gel did not affect the sensitivity of osteoclastogenesis to FG-4592, but increased sensitivity to reduced concentrations of RANKL. Co-culture with osteoblasts amplified inhibition of osteoclastogenesis by FG-4592, whether the osteoblasts were proliferating, differentiating or in the presence of exogenous M-CSF and RANKL. Osteoblast co-culture dampened the ability of high concentrations of FG-4592 to increase bone resorption.This data provides support for the therapeutic use of PHD enzyme inhibitors to improve bone formation and/or reduce bone loss for treatment of osteolytic pathologies, and indicates that FG-4592 might also act to inhibit the formation and activity of the osteoclasts that drive osteolysis.

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