ArticleThe Journal of clinical investigation2007
Mutation of the sequestosome 1 (p62) gene increases osteoclastogenesis but does not induce Paget disease.
Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 126 citations in OpenAlex.
- Critical role of AKT protein in myeloma-induced osteoclast formation and osteolysis.The Journal of biological chemistry · 2013Trial
- Role of ATF7-TAF12 interactions in the vitamin D response hypersensitivity of osteoclast precursors in Paget's disease.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2013Trial
- Trial
- Article
- A Review of Signaling Transduction Mechanisms in Osteoclastogenesis Regulation by Autophagy, Inflammation, and Immunity.International journal of molecular sciences · 2022Review
- P62/SQSTM1 beyond Autophagy: Physiological Role and Therapeutic Applications in Laboratory and Domestic Animals.Life (Basel, Switzerland) · 2022Review
- Attenuated clinical and osteoclastic phenotypes of Paget's disease of bone linked to the p.Pro392Leu/SQSTM1 mutation by a rare variant in the DOCK6 gene.BMC medical genomics · 2022Article
- Review
- Autophagic Mediators in Bone Marrow Niche Homeostasis.Advances in experimental medicine and biology · 2022Article
- 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.Calcified tissue international · 2019Review
- The Autophagy in Osteoimmonology: Self-Eating, Maintenance, and Beyond.Frontiers in endocrinology · 2019Review
- Zoledronic acid prevents pagetic-like lesions and accelerated bone loss in the p62Disease models & mechanisms · 2018Article
- Multiple Myeloma and Bone: The Fatal Interaction.Cold Spring Harbor perspectives in medicine · 2018Review
- A quest for clarity in bone erosion: The role of sequestosome 1 in Paget's disease of bone.The Journal of biological chemistry · 2018Article
- p62/sequestosome 1 deficiency accelerates osteoclastogenesisThe Journal of biological chemistry · 2018Article
- Effect of a rare genetic variant of TM7SF4 gene on osteoclasts of patients with Paget's disease of bone.BMC medical genetics · 2017Article
- A FKBP5 mutation is associated with Paget's disease of bone and enhances osteoclastogenesis.Experimental & molecular medicine · 2017Article
- Clinical and Genetic Advances in Paget's Disease of Bone: a Review.Clinical reviews in bone and mineral metabolism · 2017Review
- Measles virus nucleocapsid protein increases osteoblast differentiation in Paget's disease.The Journal of clinical investigation · 2016Article
Corrections and comments
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Authors and funding
10 authors at 8 institutions in 2 countries.
Funding
Abstract
Paget disease is the most exaggerated example of abnormal bone remodeling, with the primary cellular abnormality in the osteoclast. Mutations in the p62 (sequestosome 1) gene occur in one-third of patients with familial Paget disease and in a minority of patients with sporadic Paget disease, with the P392L amino acid substitution being the most commonly observed mutation. However, it is unknown how p62(P392L) mutation contributes to the development of this disease. To determine the effects of p62(P392L) expression on osteoclasts in vitro and in vivo, we introduced either the p62(P392L) or WT p62 gene into normal osteoclast precursors and targeted p62(P392L) expression to the osteoclast lineage in transgenic mice. p62(P392L)-transduced osteoclast precursors were hyperresponsive to receptor activator of NF-kappaB ligand (RANKL) and TNF-alpha and showed increased NF-kappaB signaling but did not demonstrate increased 1,25-(OH)(2)D(3) responsivity, TAF(II)-17 expression, or nuclear number per osteoclast. Mice expressing p62(P392L) developed increased osteoclast numbers and progressive bone loss, but osteoblast numbers were not coordinately increased, as is seen in Paget disease. These results indicate that p62(P392L) expression on osteoclasts is not sufficient to induce the full pagetic phenotype but suggest that p62 mutations cause a predisposition to the development of Paget disease by increasing the sensitivity of osteoclast precursors to osteoclastogenic cytokines.
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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.