ArticleThe Journal of biological chemistry2015
Progranulin and a five transmembrane domain-containing receptor-like gene are the key components in receptor activator of nuclear factor κB (RANK)-dependent formation of multinucleated osteoclasts.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Developmental divergence in gene regulation underlies trophic innovation in Lake Victoria cichlids.Proceedings. Biological sciences · 2026Article
- Progranulin Protects Against Osteoporosis by Regulating Osteoclast and Osteoblast Balance via TNFR Pathway.Journal of cellular and molecular medicine · 2025Article
- Progranulin deficiency associates with postmenopausal osteoporosis via increasing ubiquitination of estrogen receptor α.Genes & diseases · 2025Article
- Molecular mechanisms and targeted therapy of progranulin in metabolic diseases.Frontiers in endocrinology · 2025Review
- Delayed Tooth Development and the Impaired Differentiation of Stem/Progenitor Cells in Incisors from Type 2 Diabetes Mice.International journal of molecular sciences · 2024Article
- Stephanine Protects Against Osteoporosis by Suppressing Osteoclastogenesis via Inhibition of the RANKL-RANK Interaction.Journal of cellular and molecular medicine · 2024Article
- Progranulinopathy: A diverse realm of disorders linked to progranulin imbalances.Cytokine & growth factor reviews · 2024Review
- Progranulin, a moderator of estrogen/estrogen receptor α binding, regulates bone homeostasis through PERK/p-eIF2 signaling pathway.Journal of molecular medicine (Berlin, Germany) · 2022Article
- Progranulin promotes osteogenic differentiation of periodontal membrane stem cells in both inflammatory and non-inflammatory conditions.The Journal of international medical research · 2021Article
- DR3 and its ligands take roles in periodontium remodeling during orthodontic tooth movement.Journal of dental sciences · 2021Article
- Macrophages Switch to an Osteo-Modulatory Profile Upon RANKL Induction in a Medaka (JBMR plus · 2020Article
- Computational Analysis of the Global Effects ofGenes · 2020Article
- Female-Specific Role of Progranulin to Suppress Bone Formation.Endocrinology · 2019Article
- The Endogenous GRP78 Interactome in Human Head and Neck Cancers: A Deterministic Role of Cell Surface GRP78 in Cancer Stemness.Scientific reports · 2018Article
- The dynamic evolution of rheumatology in Korea.Nature reviews. Rheumatology · 2016Review
- Progranulin concentration in relation to bone mineral density among obese individuals.Archives of endocrinology and metabolismArticle
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Homeostatic bone remodeling is vital to maintain healthy bone tissue. Although the receptor activator of nuclear factor κB ligand (RANKL)/RANK axis is considered the master regulator of osteoclastogenesis, the underlying mechanisms including cell fusion remain incompletely defined. Here, we introduce a new axis in the formation of multinucleated cells via RANK signaling: the progranulin (PGRN)/PIRO (PGRN-induced receptor-like gene during osteoclastogenesis) axis. When mouse bone marrow-derived macrophages were stimulated with PGRN in the presence of RANKL, explosive OC formation was observed. PGRN knockdown experiments suggested that endogenous PGRN is an essential component of the RANKL/RANK axis. Our efforts for identifying genes that are induced by PGRN unveiled a remarkably induced (20-fold) gene named PIRO. Substantial PGRN and PIRO expression was detected after 2 and 3 days, respectively, suggesting that their sequential induction. PIRO was predicted to be a five transmembrane domain-containing receptor-like molecule. The tissue distribution of PGRN and PIRO mRNA expression suggested that bone marrow cells are the most suitable niche. Mouse and human PIRO are part of a multigene family. Knockdown experiments suggested that PIRO is a direct target for the formation of multinucleated cells by PGRN. PGRN levels were also substantially higher in ovariectomized mice than in sham control mice. These observations suggest that PGRN and PIRO form a new regulatory axis in osteoclastogenesis that is included in RANK signaling in cell fusion and OC resorption of osteoclastogenesis, which may offer a novel therapeutic modality for osteoporosis and other bone-associated diseases.
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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.