ArticleHuman molecular genetics2008
A SQSTM1/p62 mutation linked to Paget's disease increases the osteoclastogenic potential of the bone microenvironment.
Article in Human molecular genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 90 citations in OpenAlex.
- 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
- Mature-onset obesity in p62-deficient male mice maintains skeletal muscle mass despite metabolic dysfunction.Physiological reports · 2026Article
- Article
- The thrombin receptor PAR1 orchestrates changes in lymphatic endothelial cell junction morphology to augment lymphatic drainage during lung injury.Nature cardiovascular research · 2025Article
- Paget's Disease of the Bone and Lynch Syndrome: An Exceptional Finding.Diagnostics (Basel, Switzerland) · 2023Article
- Article
- 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
- Autophagic Mediators in Bone Marrow Niche Homeostasis.Advances in experimental medicine and biology · 2022Article
- Update on the pathogenesis and genetics of Paget's disease of bone.Frontiers in cell and developmental biology · 2022Review
- Impact of the Endocannabinoid System on Bone Formation and Remodeling in p62 KO Mice.Frontiers in pharmacology · 2022Article
- Paget's disease of the jaws: Histopathological features of a series of 31 cases.Acta odontologica latinoamericana : AOL · 2021Article
- Autophagy in major human diseases.The EMBO journal · 2021Review
- Different Roles of p62 (SQSTM1) Isoforms in Keratin-Related Protein Aggregation.International journal of molecular sciences · 2021Article
- Immunoexpression pattern of autophagy mediators in alveolar bone osteoclasts following estrogen withdrawal in female rats.Journal of molecular histology · 2021Article
- Mendelian neurodegenerative disease genes involved in autophagy.Cell discovery · 2020Review
- Paget's Disease of Bone.Calcified tissue international · 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
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Paget's disease of bone (PDB) is the second most common bone disease and is characterized by focal bone lesions which contain large numbers of abnormal osteoclasts (OCLs) and very active normal osteoblasts in a highly osteoclastogenic marrow microenvironment. The etiology of PDB is not well understood and both environmental and genetic causes have been implicated in its pathogenesis. Mutations in the SQSTM1/p62 gene have been identified in up to 30% of Paget's patients. To determine if p62 mutation is sufficient to induce PDB, we generated mice harboring a mutation causing a P-to-L (proline-to-leucine) substitution at residue 394 (the murine equivalent of human p62(P392L), the most common PDB-associated mutation). Bone marrow cultures from p62(P394L) mice formed increased numbers of OCLs in response to receptor activator of NF-kappaB ligand (RANKL), tumor necrosis factor alpha (TNF-alpha) or 1alpha,25-(OH)(2)D(3), similar to PDB patients. However, purified p62(P394L) OCL precursors depleted of stromal cells were no longer hyper-responsive to 1alpha,25-(OH)(2)D(3), suggesting effects of the p62(P394L) mutation on the marrow microenvironment in addition to direct effects on OCLs. Co-cultures of purified p62(P394L) stromal cells with either wild-type (WT) or p62(P394L) OCL precursors formed more OCLs than co-cultures containing WT stromal cells due to increased RANKL production by the mutant stromal cells. However, despite the enhanced osteoclastogenic potential of both OCL precursors and marrow stromal cells, the p62(P394L) mice had histologically normal bones. These results indicate that this PDB-associated p62 mutation is not sufficient to induce PDB and suggest that additional factors acting together with p62 mutation are necessary for the development of PDB in vivo.
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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.