ArticleBiochimica et biophysica acta. Molecular and cell biology of lipids2017
Phosphoglycerol dihydroceramide, a distinctive ceramide produced by Porphyromonas gingivalis, promotes RANKL-induced osteoclastogenesis by acting on non-muscle myosin II-A (Myh9), an osteoclast cell fusion regulatory factor.
Article in Biochimica et biophysica acta. Molecular and cell biology of lipids, 2017. 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, 47 citations in OpenAlex.
- Article
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- Transplantation of AQP1-overexpressing mitochondria attenuates periodontitis-associated bone loss by regulating mitochondria-ER contacts of macrophages.Journal of nanobiotechnology · 2026Article
- Porphyromonas gingivalis-Derived Virulence Lipids Accelerate Osteoclastogenesis Independently of High Mobility Group Box Protein-1 Canonical Signaling.Molecular oral microbiology · 2026Article
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- Age- and sex-associated effects of C18 ceramide sphingolipids on osteoclastogenesis in experimental models of Gulf War Illness.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Oral microbiome, periodontal disease and systemic bone-related diseases in the era of homeostatic medicine.Journal of advanced research · 2025Review
- Role of Canonical and Non-Canonical Sphingolipids and their Metabolic Enzymes in Bone Health.Current osteoporosis reports · 2025Review
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- Inhibition of SARS-CoV-2 infection byMicrobiology spectrum · 2024Article
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- In Situ Raman Study of Neurodegenerated Human Neuroblastoma Cells Exposed to Outer-Membrane Vesicles Isolated fromInternational journal of molecular sciences · 2023Article
- Dihydroceramides Derived from Bacteroidetes Species Sensitize TRPV1 Channels.International journal of molecular sciences · 2023Article
- Molecular systems architecture of host-microbiome interactions in periodontitis.JADA foundational science · 2023Review
- Crosstalk between dihydroceramides produced by Porphyromonas gingivalis and host lysosomal cathepsin B in the promotion of osteoclastogenesis.Journal of cellular and molecular medicine · 2022Article
- Mechanisms of bone remodeling and therapeutic strategies in chronic apical periodontitis.Frontiers in cellular and infection microbiology · 2022Review
- Association betweenFrontiers in cellular and infection microbiology · 2022Review
- Sphingolipid-Containing Outer Membrane Vesicles Serve as a Delivery Vehicle To Limit Macrophage Immune Response to Porphyromonas gingivalis.Infection and immunity · 2021Article
- miR-6807-5p Inhibited the Odontogenic Differentiation of Human Dental Pulp Stem Cells Through Directly Targeting METTL7A.Frontiers in cell and developmental biology · 2021Article
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Authors and funding
14 authors at 8 institutions in 4 countries.
Funding
Abstract
Among several virulence factors produced by the periodontal pathogen Porphyromonas gingivalis (Pg), a recently identified novel class of dihydroceramide lipids that contains a long acyl-chain has the potential to play a pathogenic role in periodontitis because of its higher level of tissue penetration compared to other lipid classes produced by Pg. However, the possible impact of Pg ceramides on osteoclastogenesis is largely unknown. In the present study, we report that the phosphoglycerol dihydroceramide (PGDHC) isolated from Pg enhanced osteoclastogenesis in vitro and in vivo. Using RAW264.7 cells, in vitro assays indicated that PGDHC can promote RANKL-induced osteoclastogenesis by generating remarkably larger TRAP+ multinuclear osteoclasts compared to Pg LPS in a TLR2/4-independent manner. According to fluorescent confocal microscopy, co-localization of non-muscle myosin II-A (Myh9) and PGDHC was observed in the cytoplasm of osteoclasts, indicating the membrane-permeability of PGDHC. Loss- and gain-of-function assays using RNAi-based Myh9 gene silencing, as well as overexpression of the Myh9 gene, in RAW264.7 cells showed that interaction of PGDHC with Myh9 enhances RANKL-induced osteoclastogenesis. It was also demonstrated that PGDHC can upregulate the expression of dendritic cell-specific transmembrane protein (DC-STAMP), an important osteoclast fusogen, through signaling that involves Rac1, suggesting that interaction of PGDHC with Myh9 can elicit the cell signal that promotes osteoclast cell fusion. Taken together, our data indicated that PGDHC is a Pg-derived, cell-permeable ceramide that possesses a unique property of promoting osteoclastogenesis via interaction with Myh9 which, in turn, activates a Rac1/DC-STAMP pathway for upregulation of osteoclast cell fusion.
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