ArticleExperimental & molecular medicine2022
Phospholipase D2 controls bone homeostasis by modulating M-CSF-dependent osteoclastic cell migration and microtubule stability.
Article in Experimental & molecular medicine, 2022. 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, 22 citations in OpenAlex.
- Polydeoxyribonucleotide (PDRN) Selectively Promotes Osteoblast Differentiation Without Affecting Osteoclastogenesis.Marine drugs · 2026Article
- The Role of Follistatin-like 1 in the Cross-Talk Among Osteoclastogenesis, Bone Marrow Stromal Cell Migration, and OsteoblastogenesisBiomedicines · 2026Article
- Nanometer preparation of natural bioactive compounds for treatment of rheumatoid arthritis.Journal of pharmaceutical analysis · 2025Review
- Sinensetin serves as an AMPK activator to inhibit RANKL-induced osteoclastogenesis via osteoclast cytoskeleton reorganization.Journal of translational medicine · 2025Article
- Pim1 promotes the maintenance of bone homeostasis by regulating osteoclast function.Experimental & molecular medicine · 2025Article
- Phospholipase C β4 promotes RANKL-dependent osteoclastogenesis by interacting with MKK3 and p38 MAPK.Experimental & molecular medicine · 2025Article
- Clinical effects of phospholipase D2 in attenuating acute pancreatitis.World journal of gastroenterology · 2025Article
- TNF receptor-associated factors: promising targets of natural products for the treatment of osteoporosis.Frontiers in physiology · 2025Review
- Phospholipase D, a Novel Therapeutic Target Contributes to the Pathogenesis of Neurodegenerative and Neuroimmune Diseases.Analytical cellular pathology (Amsterdam) · 2024Review
- Myrislignan targets extracellular signal-regulated kinase (ERK) and modulates mitochondrial function to dampen osteoclastogenesis and ovariectomy-induced osteoporosis.Journal of translational medicine · 2023Article
- Functional Role of Phospholipase D in Bone Metabolism.Journal of bone metabolism · 2023Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phospholipase D2 (PLD2), a signaling protein, plays a central role in cellular communication and various biological processes. Here, we show that PLD2 contributes to bone homeostasis by regulating bone resorption through osteoclastic cell migration and microtubule-dependent cytoskeletal organization. Pld2-deficient mice exhibited a low bone mass attributed to increased osteoclast function without altered osteoblast activity. While Pld2 deficiency did not affect osteoclast differentiation, its absence promoted the migration of osteoclast lineage cells through a mechanism involving M-CSF-induced activation of the PI3K-Akt-GSK3β signaling pathway. The absence of Pld2 also boosted osteoclast spreading and actin ring formation, resulting in elevated bone resorption. Furthermore, Pld2 deletion increased microtubule acetylation and stability, which were later restored by treatment with a specific inhibitor of Akt, an essential molecule for microtubule stabilization and osteoclast bone resorption activity. Interestingly, PLD2 interacted with the M-CSF receptor (c-Fms) and PI3K, and the association between PLD2 and c-Fms was reduced in response to M-CSF. Altogether, our findings indicate that PLD2 regulates bone homeostasis by modulating osteoclastic cell migration and microtubule stability via the M-CSF-dependent PI3K-Akt-GSK3β axis.
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