ArticleBMC musculoskeletal disorders2010
Screening of protein kinase inhibitors identifies PKC inhibitors as inhibitors of osteoclastic acid secretion and bone resorption.
Article in BMC musculoskeletal disorders, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Diverse Therapeutic Potentials of Hypericin: An In-Depth Review.Current topics in medicinal chemistry · 2025Review
- Signaling pathways regulating the extracellular digestion of lipoprotein aggregates by macrophages.Molecular biology of the cell · 2024Article
- Article
- Estimation of L-carnitine levels in diabetic completely edentulous patients for implant diagnosis: A cross-sectional study.Dental research journal · 2023Article
- 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
- Hypericin targets osteoclast and prevents breast cancer-induced bone metastasis via NFATc1 signaling pathway.Oncotarget · 2018Article
- MiR-142-3p is a RANKL-dependent inducer of cell death in osteoclasts.Scientific reports · 2016Article
- Diacylglycerol Kinase ζ (DGKζ) Is a Critical Regulator of Bone Homeostasis Via Modulation of c-Fos Levels in Osteoclasts.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2015Article
- Regulation of lysosome biogenesis and functions in osteoclasts.Cell cycle (Georgetown, Tex.) · 2013Review
- A RANKL-PKCβ-TFEB signaling cascade is necessary for lysosomal biogenesis in osteoclasts.Genes & development · 2013Article
- Loss of protein kinase C-δ protects against LPS-induced osteolysis owing to an intrinsic defect in osteoclastic bone resorption.PloS one · 2013Article
- Novel drug discovery platform for spinocerebellar ataxia, using fluorescence technology targeting β-III-spectrin.The Journal of biological chemistryArticle
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBone resorption is initiated by osteoclastic acidification of the resorption lacunae. This process is mediated by secretion of protons through the V-ATPase and chloride through the chloride antiporter ClC-7. To shed light on the intracellular signalling controlling extracellular acidification, we screened a protein kinase inhibitor library in human osteoclasts.
methodsHuman osteoclasts were generated from CD14+ monocytes. The effect of different kinase inhibitors on lysosomal acidification in human osteoclasts was investigated using acridine orange for different incubation times (45 minutes, 4 and 24 hours). The inhibitors were tested in an acid influx assay using microsomes isolated from human osteoclasts. Bone resorption by human osteoclasts on bone slices was measured by calcium release. Cell viability was measured using AlamarBlue.
resultsOf the 51 compounds investigated only few inhibitors were positive in both acidification and resorption assays. Rottlerin, GF109203X, Hypericin and Ro31-8220 inhibited acid influx in microsomes and bone resorption, while Sphingosine and Palmitoyl-DL-carnitine-Cl showed low levels of inhibition. Rottlerin inhibited lysosomal acidification in human osteoclasts potently.
conclusionsIn conclusion, a group of inhibitors all indicated to inhibit PKC reduced acidification in human osteoclasts, and thereby bone resorption, indicating that acid secretion by osteoclasts may be specifically regulated by PKC in osteoclasts.
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