ArticleMolecular endocrinology (Baltimore, Md.)2009
The p62 P392L mutation linked to Paget's disease induces activation of human osteoclasts.
Article in Molecular endocrinology (Baltimore, Md.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 72 citations in OpenAlex.
- Trial
- Galectin-8 modulates human osteoclast activity partly through isoform-specific interactions.Life science alliance · 2024Article
- Paget's Disease of the Bone and Lynch Syndrome: An Exceptional Finding.Diagnostics (Basel, Switzerland) · 2023Article
- Update on the pathogenesis and genetics of Paget's disease of bone.Frontiers in cell and developmental biology · 2022Review
- Epigenetic DNA Methylation Signatures Associated With the Severity of Paget's Disease of Bone.Frontiers in cell and developmental biology · 2022Article
- Impact of the Endocannabinoid System on Bone Formation and Remodeling in p62 KO Mice.Frontiers in pharmacology · 2022Article
- miR profile in pagetic osteoclasts: from large-scale sequencing to gene expression study.Journal of molecular medicine (Berlin, Germany) · 2021Article
- Immunoexpression pattern of autophagy mediators in alveolar bone osteoclasts following estrogen withdrawal in female rats.Journal of molecular histology · 2021Article
- Paget's Disease of Bone: Osteoimmunology and Osteoclast Pathology.Current allergy and asthma reports · 2021Review
- Rab GTPases in Osteoclastic Bone Resorption and Autophagy.International journal of molecular sciences · 2020Review
- Zoledronic acid prevents pagetic-like lesions and accelerated bone loss in the p62Disease models & mechanisms · 2018Article
- p62/sequestosome 1 deficiency accelerates osteoclastogenesisThe Journal of biological chemistry · 2018Article
- Rab GTPases in Osteoclastic Endomembrane Systems.BioMed research international · 2018Review
- Lipopolysaccharide (LPS)-Induced Autophagy Is Responsible for Enhanced Osteoclastogenesis.Molecules and cells · 2017Article
- Effect of a rare genetic variant of TM7SF4 gene on osteoclasts of patients with Paget's disease of bone.BMC medical genetics · 2017Article
- Osteosarcoma: Molecular Pathogenesis and iPSC Modeling.Trends in molecular medicine · 2017Review
- Genetics of Paget's disease of bone.BoneKEy reports · 2015Review
- Article
- Genetics of Paget's disease of bone.Current osteoporosis reports · 2014Review
- Alternative splicing in osteoclasts and Paget's disease of bone.BMC medical genetics · 2014Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations of the gene encoding p62/SQSTM1 have been described in Paget's disease of bone (PDB), identifying p62 as an important player in osteoclast signaling. We investigated the phenotype of osteoclasts differentiated from peripheral blood monocytes obtained from healthy donors or PDB patients, all genotyped for the presence of a mutation in the p62 ubiquitin-associated domain. The cohort included PDB patients carrying or not the p62 P392L mutation and healthy donors carrying or not this mutation. Osteoclasts from PDB patients were more numerous, contained more nuclei, were more resistant to apoptosis, and had a greater ability to resorb bone than their normal counterparts, regardless of whether the p62 mutation was present or not. A strong increase in p62 expression was observed in PDB osteoclasts. The presence of the p62(P392L) gene in cells from healthy carriers conferred a unique, intermediate osteoclast phenotype. In addition, we report that two survival-promoting kinases, protein kinase Czeta and phosphoinositide-dependent protein kinase 1, were associated with p62 in response to receptor activator of NF-kappaB ligand (RANKL) stimulation in controls and before RANKL was added in PDB osteoclasts. In transfected osteoclasts derived from cord blood monocytes, the p62 P392L mutation contributed to increased activation of kinases protein kinase Czeta/lambda and phosphoinositide-dependent protein kinase 1, along with basal activation of NF-kappaB, independently of RANKL stimulation. These findings clearly indicate that the overexpression of p62 in PDB patients induces important shifts in the pathways activated by RANKL and up-regulates osteoclast functions. Moreover, the most-commonly reported p62 mutation, P392L, certainly contributes to the overactive state of osteoclasts in PDB.
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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.