ArticlePloS one2010
NIK stabilization in osteoclasts results in osteoporosis and enhanced inflammatory osteolysis.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 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
33 citing papers in PubMed, 48 citations in OpenAlex.
- Targeting the osteoporotic bone microenvironment: Mechanistic insight and therapeutic biomaterials for accelerating bone regeneration.Bioactive materials · 2026Review
- Potential of IL-33 as a Novel Myokine in Sarcopenia- Osteoporosis Communication: Insights from Mendelian Randomization.Endocrine, metabolic & immune disorders drug targets · 2026Article
- HDAC5-Mediated Acetylation of p100 Suppresses Its Processing.International dental journal · 2023Article
- From Stem to Sternum: The Role of Shp2 in the Skeleton.Calcified tissue international · 2023Review
- Regulation of osteoclast-mediated bone resorption by microRNA.Cellular and molecular life sciences : CMLS · 2022Review
- Conditional loss of IKKα in Osterix + cells has no effect on bone but leads to age-related loss of peripheral fat.Scientific reports · 2022Article
- NF-κB signaling in inflammation and cancer.MedComm · 2021Review
- Article
- Targeting NF-κB-Inducing Kinase (NIK) in Immunity, Inflammation, and Cancer.International journal of molecular sciences · 2020Review
- miR-346-3p promotes osteoclastogenesis via inhibiting TRAF3 gene.In vitro cellular & developmental biology. Animal · 2020Article
- Review
- NF-κB Signaling Regulates Physiological and Pathological Chondrogenesis.International journal of molecular sciences · 2019Review
- Conditional Activation of NF-κB Inducing Kinase (NIK) in the Osteolineage Enhances Both Basal and Loading-Induced Bone Formation.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Article
- Article
- Manipulation of the Alternative NF-κB Pathway in Mice Has Sexually Dimorphic Effects on Bone.JBMR plus · 2019Article
- TRAF molecules in inflammation and inflammatory diseases.Current pharmacology reports · 2018Article
- Bone Remodeling and the Role of TRAF3 in Osteoclastic Bone Resorption.Frontiers in immunology · 2018Review
- The non-canonical NF-κB pathway in immunity and inflammation.Nature reviews. Immunology · 2017Review
- MYC-dependent oxidative metabolism regulates osteoclastogenesis via nuclear receptor ERRα.The Journal of clinical investigation · 2017Article
- RANKL cytokine enhances TNF-induced osteoclastogenesis independently of TNF receptor associated factor (TRAF) 6 by degrading TRAF3 in osteoclast precursors.The Journal of biological chemistry · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundMaintenance of healthy bone requires the balanced activities of osteoclasts (OCs), which resorb bone, and osteoblasts, which build bone. Disproportionate action of OCs is responsible for the bone loss associated with postmenopausal osteoporosis and rheumatoid arthritis. NF-κB inducing kinase (NIK) controls activation of the alternative NF-κB pathway, a critical pathway for OC differentiation. Under basal conditions, TRAF3-mediated NIK degradation prevents downstream signaling, and disruption of the NIK:TRAF3 interaction stabilizes NIK leading to constitutive activation of the alternative NF-κB pathway. METHODOLOGY/PRINCIPAL
findingsUsing transgenic mice with OC-lineage expression of NIK lacking its TRAF3 binding domain (NT3), we now find that alternative NF-κB activation enhances not only OC differentiation but also OC function. Activating NT3 with either lysozyme M Cre or cathepsinK Cre causes high turnover osteoporosis with increased activity of OCs and osteoblasts. In vitro, NT3-expressing precursors form OCs more quickly and at lower doses of RANKL. When cultured on bone, they exhibit larger actin rings and increased resorptive activity. OC-specific NT3 transgenic mice also have an exaggerated osteolytic response to the serum transfer model of arthritis.
conclusionsConstitutive activation of NIK drives enhanced osteoclastogenesis and bone resorption, both in basal conditions and in response to inflammatory stimuli.
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What OpenQuestion holds
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.