ArticlePloS one2013
Loss of protein kinase C-δ protects against LPS-induced osteolysis owing to an intrinsic defect in osteoclastic bone resorption.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- RUFY4 deletion prevents pathological bone loss by blocking endo-lysosomal trafficking of osteoclasts.Bone research · 2024Article
- Enhanced understanding of cinnamaldehyde's therapeutic potential in osteoarthritis through bioinformatics and mechanistic validation of its anti-apoptotic effect.Frontiers in medicine · 2024Article
- Article
- Small molecule inhibitors of osteoarthritis: Current development and future perspective.Frontiers in physiology · 2023Review
- The metabolomics of a protein kinase C delta (PKCδ) knock-out mouse model.Metabolomics : Official journal of the Metabolomic Society · 2022Article
- Inhibition of Neddylation Suppresses Osteoclast Differentiation and Function In Vitro and Alleviates Osteoporosis In Vivo.Biomedicines · 2022Article
- Osteoclast fusion and bone loss are restricted by interferon inducible guanylate binding proteins.Nature communications · 2021Article
- Article
- PKC-δ deficiency in B cells displays osteopenia accompanied with upregulation of RANKL expression and osteoclast-osteoblast uncoupling.Cell death & disease · 2020Article
- Sotrastaurin, a PKC inhibitor, attenuates RANKL-induced bone resorption and attenuates osteochondral pathologies associated with the development of OA.Journal of cellular and molecular medicine · 2020Article
- Conditional Knockout of PKC-δ in Osteoclasts Favors Bone Mass Accrual in Males Due to Decreased Osteoclast Function.Frontiers in cell and developmental biology · 2020Article
- Morc3 mutant mice exhibit reduced cortical area and thickness, accompanied by altered haematopoietic stem cells niche and bone cell differentiation.Scientific reports · 2016Article
- Protein kinase C delta null mice exhibit structural alterations in articular surface, intra-articular and subchondral compartments.Arthritis research & therapy · 2015Article
- Choline kinase β mutant mice exhibit reduced phosphocholine, elevated osteoclast activity, and low bone mass.The Journal of biological chemistry · 2015Article
- The osteogenic or adipogenic lineage commitment of human mesenchymal stem cells is determined by protein kinase C delta.BMC cell biology · 2014Article
- Andrographolide suppresses RANKL-induced osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo.British journal of pharmacology · 2014Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone remodeling is intrinsically regulated by cell signaling molecules. The Protein Kinase C (PKC) family of serine/threonine kinases is involved in multiple signaling pathways including cell proliferation, differentiation, apoptosis and osteoclast biology. However, the precise involvement of individual PKC isoforms in the regulation of osteoclast formation and bone homeostasis remains unclear. Here, we identify PKC-δ as the major PKC isoform expressed among all PKCs in osteoclasts; including classical PKCs (-α, -β and -γ), novel PKCs (-δ, -ε, -η and -θ) and atypical PKCs (-ι/λ and -ζ). Interestingly, pharmacological inhibition and genetic ablation of PKC-δ impairs osteoclastic bone resorption in vitro. Moreover, disruption of PKC-δ activity protects against LPS-induced osteolysis in mice, with osteoclasts accumulating on the bone surface failing to resorb bone. Treatment with the PKC-δ inhibitor Rottlerin, blocks LPS-induced bone resorption in mice. Consistently, PKC-δ deficient mice exhibit increased trabeculae bone containing residual cartilage matrix, indicative of an osteoclast-rich osteopetrosis phenotype. Cultured ex vivo osteoclasts derived from PKC-δ null mice exhibit decreased CTX-1 levels and MARKS phosphorylation, with enhanced formation rates. This is accompanied by elevated gene expression levels of cathepsin K and PKC -α, -γ and -ε, as well as altered signaling of pERK and pcSrc416/527 upon RANKL-induction, possibly to compensate for the defects in bone resorption. Collectively, our data indicate that PKC-δ is an intrinsic regulator of osteoclast formation and bone resorption and thus is a potential therapeutic target for pathological osteolysis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.