Protaetia brevitarsis Extract Attenuates RANKL-Induced Osteoclastogenesis by Inhibiting the JNK/NF-κB/PLCγ2 Signaling Pathway. 2023

Hye-Yeon Jang, and Jeong-Mi Kim, and Jong-Suk Kim, and Byeong-Soo Kim, and Young-Rae Lee, and Jun Sang Bae
Infectious Diseases Therapeutic Research Center, Korea Research Institute of Chemical Technology (KRICT), Daejeon 34114, Republic of Korea.

Protaetia brevitarsis (PB)-derived bioactive substances have been used as food and medicine in many Asian countries because of their antioxidant, antidiabetic, anti-cancer, and hepatoprotective properties. However, the effect of PB extracts (PBE) on osteoclast differentiation is unclear. In this study, we investigated the effect of PBE on RANKL-induced osteoclastogenesis in mouse bone marrow-derived macrophages (BMMs). To investigate the cytotoxicity of PBE, the viability of BMMs was confirmed via MTT assay. Tartrate-resistant acid phosphatase (TRAP) staining and pit assays were performed to confirm the inhibitory effect of PBE on osteoclast differentiation and bone resorption. The expression levels of osteoclast differentiation-related genes and proteins were evaluated using quantitative real-time PCR and Western blotting. PBE attenuated osteoclastogenesis in BMMs in TRAP and pit assays without cytotoxicity. The expression levels of osteoclast marker genes and proteins induced by RANKL were decreased after PBE treatment. PBE suppressed osteoclastogenesis by inhibiting the RANKL-induced activated JNK/NF-κB/PLCγ2 signaling pathway and the expression of NFATc1 and c-Fos. Collectively, these results suggest that PBE could be a potential therapeutic strategy or functional product for osteoclast-related bone disease.

UI MeSH Term Description Entries
D010010 Osteoclasts A large multinuclear cell associated with the BONE RESORPTION. An odontoclast, also called cementoclast, is cytomorphologically the same as an osteoclast and is involved in CEMENTUM resorption. Odontoclasts,Cementoclast,Cementoclasts,Odontoclast,Osteoclast
D010012 Osteogenesis The process of bone formation. Histogenesis of bone including ossification. Bone Formation,Ossification, Physiologic,Endochondral Ossification,Ossification,Ossification, Physiological,Osteoclastogenesis,Physiologic Ossification,Endochondral Ossifications,Ossification, Endochondral,Ossifications,Ossifications, Endochondral,Osteoclastogeneses,Physiological Ossification
D001862 Bone Resorption Bone loss due to osteoclastic activity. Bone Loss, Osteoclastic,Osteoclastic Bone Loss,Bone Losses, Osteoclastic,Bone Resorptions,Loss, Osteoclastic Bone,Losses, Osteoclastic Bone,Osteoclastic Bone Losses,Resorption, Bone,Resorptions, Bone
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016328 NF-kappa B Ubiquitous, inducible, nuclear transcriptional activator that binds to enhancer elements in many different cell types and is activated by pathogenic stimuli. The NF-kappa B complex is a heterodimer composed of two DNA-binding subunits: NF-kappa B1 and relA. Immunoglobulin Enhancer-Binding Protein,NF-kappa B Complex,Nuclear Factor kappa B,Transcription Factor NF-kB,kappa B Enhancer Binding Protein,Ig-EBP-1,NF-kB,NF-kappaB,Nuclear Factor-Kappab,Complex, NF-kappa B,Enhancer-Binding Protein, Immunoglobulin,Factor NF-kB, Transcription,Factor-Kappab, Nuclear,Ig EBP 1,Immunoglobulin Enhancer Binding Protein,NF kB,NF kappa B Complex,NF kappaB,NF-kB, Transcription Factor,Nuclear Factor Kappab,Transcription Factor NF kB
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D051966 Phospholipase C gamma A phosphoinositide phospholipase C subtype that is primarily regulated by PROTEIN-TYROSINE KINASES. It is structurally related to PHOSPHOLIPASE C DELTA with the addition of SRC HOMOLOGY DOMAINS and pleckstrin homology domains located between two halves of the CATALYTIC DOMAIN. PLC gamma1,PLC-gamma,PLC-gamma 2,PLC-gamma D,PLCgamma2,Phospholipase C gamma 1,Phospholipase C gamma 2,Phospholipase C gamma D,Phospholipase C gamma1,Phospholipase C gamma2,Phospholipase C gammaD,PLC gamma 2
D053245 RANK Ligand A transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RECEPTOR ACTIVATOR OF NUCLEAR FACTOR-KAPPA B and OSTEOPROTEGERIN. It plays an important role in regulating OSTEOCLAST differentiation and activation. Tumor Necrosis Factor Ligand Superfamily Member 11,CD254 Antigen,OPGL Protein,Osteoclast Differentiation Factor,Osteoprotegerin Ligand,RANKL Protein,Receptor Activator of Nuclear Factor-kappa B Ligand,Receptor Activator of Nuclear Factor-kappaB Ligand,TNF Superfamily, Member 11,TRANCE Protein,Tumor Necrosis Factor-Related Activation-Induced Cytokine,Antigen, CD254,Differentiation Factor, Osteoclast,Receptor Activator of Nuclear Factor kappa B Ligand,Receptor Activator of Nuclear Factor kappaB Ligand,Tumor Necrosis Factor Related Activation Induced Cytokine
D020935 MAP Kinase Signaling System An intracellular signaling system involving the mitogen-activated protein kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade. MAP Kinase Cascade,MAP Kinase Module,MAP Kinase Signaling Cascade,MAP Kinase Signaling Pathway,MAP Kinase Signaling Pathways,ERK Pathway,ERK Signal Tranduction Pathway,ERK1 and ERK2 Pathway,ERK1-2 Pathway,JNK Pathway,JNK Signaling Pathway,MAP Kinase Modules,MAP Kinase Signaling Cascades,MEK-ERK Pathway,p38 Kinase Pathway,p38 Kinase Signaling Pathway,Cascade, MAP Kinase,ERK Pathways,ERK1 2 Pathway,ERK1-2 Pathways,JNK Pathways,JNK Signaling Pathways,Kinase Cascade, MAP,Kinase Pathway, p38,Kinase Pathways, p38,MAP Kinase Cascades,MEK ERK Pathway,MEK-ERK Pathways,Module, MAP Kinase,Pathway, ERK,Pathway, ERK1-2,Pathway, JNK,Pathway, JNK Signaling,Pathway, MEK-ERK,Pathway, p38 Kinase,Pathways, ERK,Pathways, ERK1-2,Pathways, JNK,Pathways, JNK Signaling,Pathways, MEK-ERK,Pathways, p38 Kinase,Signaling Pathway, JNK,Signaling Pathways, JNK,p38 Kinase Pathways

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