ArticleThe Journal of biological chemistry2014
Secretion of a truncated osteopetrosis-associated transmembrane protein 1 (OSTM1) mutant inhibits osteoclastogenesis through down-regulation of the B lymphocyte-induced maturation protein 1 (BLIMP1)-nuclear factor of activated T cells c1 (NFATc1) axis.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- WDR23 prevents bone loss by promoting autophagic degradation of TRAF6 in osteoclastogenesis.Bone research · 2026Article
- Osteopetrosis: Pathogenesis, Clinical Management, and Emerging Therapies.Current osteoporosis reports · 2026Review
- TDAG51 promotes transcription factor FoxO1 activity during LPS-induced inflammatory responses.The EMBO journal · 2023Article
- 1,3-Dibenzyl-5-Fluorouracil Prevents Ovariectomy-Induced Bone Loss by Suppressing Osteoclast Differentiation.Immune network · 2022Article
- Pax5 Negatively Regulates Osteoclastogenesis through Downregulation of Blimp1.International journal of molecular sciences · 2021Article
- Osteoclast Fusion: Physiological Regulation of Multinucleation through Heterogeneity-Potential Implications for Drug Sensitivity.International journal of molecular sciences · 2020Review
- Ostm1 from Mouse to Human: Insights into Osteoclast Maturation.International journal of molecular sciences · 2020Review
- TDAG51 is a crucial regulator of maternal care and depressive-like behavior after parturition.PLoS genetics · 2019Article
- Anemonin Attenuates RANKL-Induced Osteoclastogenesis and Ameliorates LPS-Induced Inflammatory Bone Loss in MiceFrontiers in pharmacology · 2019Article
- Regulation of Osteoclast Differentiation by Cytokine Networks.Immune network · 2018Review
- Genetics of Osteopetrosis.Current osteoporosis reports · 2018Review
- Generation of an osteoblast-based artificial niche that supports in vitro B lymphopoiesis.Experimental & molecular medicine · 2017Article
- Interaction of Tumor Necrosis Factor Receptor-associated Factor 6 (TRAF6) and Vav3 in the Receptor Activator of Nuclear Factor κB (RANK) Signaling Complex Enhances Osteoclastogenesis.The Journal of biological chemistry · 2016Article
- Sirt6 cooperates with Blimp1 to positively regulate osteoclast differentiation.Scientific reports · 2016Article
- Regulatory-auxiliary subunits of CLC chloride channel-transport proteins.The Journal of physiology · 2015Review
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic mutations in osteoclastogenic genes are closely associated with osteopetrotic bone diseases. Genetic defects in OSTM1 (osteopetrosis-associated transmembrane protein 1) cause autosomal recessive osteopetrosis in humans. In particular, OSTM1 mutations that exclude the transmembrane domain might lead to the production of a secreted form of truncated OSTM1. However, the precise role of the secreted form of truncated OSTM1 remains unknown. In this study, we analyzed the functional role of truncated OSTM1 in osteoclastogenesis. Here, we showed that a secreted form of truncated OSTM1 binds to the cell surface of osteoclast (OC) precursors and inhibits the formation of multinucleated OCs through the reduction of cell fusion and survival. Truncated OSTM1 significantly inhibited the expression of OC marker genes through the down-regulation of the BLIMP1 (B lymphocyte-induced maturation protein 1)-NFATc1 (nuclear factor of activated T cells c1) axis. Finally, we demonstrated that truncated OSTM1 reduces lipopolysaccharide-induced bone destruction in vivo. Thus, these findings suggest that autosomal recessive osteopetrosis patients with an OSTM1 gene mutation lacking the transmembrane domain produce a secreted form of truncated OSTM1 that inhibits osteoclastogenesis.
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