ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2012
Protein kinase C-delta deficiency perturbs bone homeostasis by selective uncoupling of cathepsin K secretion and ruffled border formation in osteoclasts.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
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- Enhanced understanding of cinnamaldehyde's therapeutic potential in osteoarthritis through bioinformatics and mechanistic validation of its anti-apoptotic effect.Frontiers in medicine · 2024Article
- Molecular Basis beyond Interrelated Bone Resorption/Regeneration in Periodontal Diseases: A Concise Review.International journal of molecular sciences · 2023Review
- Small molecule inhibitors of osteoarthritis: Current development and future perspective.Frontiers in physiology · 2023Review
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- PERK signaling pathway in bone metabolism: Friend or foe?Cell proliferation · 2021Review
- Functional proteomic analysis reveals roles for PKCδ in regulation of cell survival and cell death: Implications for cancer pathogenesis and therapy.Advances in biological regulation · 2020Article
- 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
- Osteoimmunology: A Current Update of the Interplay Between Bone and the Immune System.Frontiers in immunology · 2020Review
- Article
- Importance of the Conserved Carboxyl-Terminal CNOT1 Binding Domain to Tristetraprolin ActivityMolecular and cellular biology · 2019Article
- MARCKS and Lung Disease.American journal of respiratory cell and molecular biology · 2019Review
- oxLDL inhibits differentiation and functional activity of osteoclasts via scavenger receptor-A mediated autophagy and cathepsin K secretion.Scientific reports · 2018Article
- A Knock-In Tristetraprolin (TTP) Zinc Finger Point Mutation in Mice: Comparison with Complete TTP Deficiency.Molecular and cellular biology · 2018Article
- Bone matrix components activate the NLRP3 inflammasome and promote osteoclast differentiation.Scientific reports · 2017Article
- Actin-binding protein coronin 1A controls osteoclastic bone resorption by regulating lysosomal secretion of cathepsin K.Scientific reports · 2017Article
- In vitro model of bone to facilitate measurement of adhesion forces and super-resolution imaging of osteoclasts.Scientific reports · 2016Article
- Tmem178 acts in a novel negative feedback loop targeting NFATc1 to regulate bone mass.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Bone homeostasis requires stringent regulation of osteoclasts, which secrete proteolytic enzymes to degrade the bone matrix. Despite recent progress in understanding how bone resorption occurs, the mechanisms regulating osteoclast secretion, and in particular the trafficking route of cathepsin K vesicles, remain elusive. Using a genetic approach, we describe the requirement for protein kinase C-delta (PKCδ) in regulating bone resorption by affecting cathepsin K exocytosis. Importantly, PKCδ deficiency does not perturb formation of the ruffled border or trafficking of lysosomal vesicles containing the vacuolar-ATPase (v-ATPase). Mechanistically, we find that cathepsin K exocytosis is controlled by PKCδ through modulation of the actin bundling protein myristoylated alanine-rich C-kinase substrate (MARCKS). The relevance of our finding is emphasized in vivo because PKCδ-/- mice exhibit increased bone mass and are protected from pathological bone loss in a model of experimental postmenopausal osteoporosis. Collectively, our data provide novel mechanistic insights into the pathways that selectively promote secretion of cathepsin K lysosomes independently of ruffled border formation, providing evidence of the presence of multiple mechanisms that regulate lysosomal exocytosis in osteoclasts.
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Registered trials
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.