ArticleProceedings of the National Academy of Sciences of the United States of America2005
Central IL-1 receptor signaling regulates bone growth and mass.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 77 citations in OpenAlex.
- Neural regulation of bone: from central neural circuits to peripheral innervation of the skeletal stem cell niche.Bone research · 2026Review
- Pyroptosis: A spoiler of peaceful coexistence between cells in degenerative bone and joint diseases.Journal of advanced research · 2025Review
- The role of DNA methylation on gene expression in the vertebrae of ancestrally benzo[a]pyrene exposed F1 and F3 male medaka.Epigenetics · 2023Article
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- Germline Saturation Mutagenesis Induces Skeletal Phenotypes in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2021Article
- A Genomic Approach to Delineating the Occurrence of Scoliosis in Arthrogryposis Multiplex Congenita.Genes · 2021Article
- Interleukin-1 induces receptor activator of nuclear factor-κB ligand-independent osteoclast differentiation in RAW264.7 cells.Experimental and therapeutic medicine · 2021Article
- A genome-wide association study in mice reveals a role for Rhbdf2 in skeletal homeostasis.Scientific reports · 2020Article
- "Inflammaging" and bone in the OsteoLaus cohort.Immunity & ageing : I & A · 2020Article
- MyD88 and IL-1R signaling drive antibacterial immunity and osteoclast-driven bone loss during Staphylococcus aureus osteomyelitis.PLoS pathogens · 2019Article
- Impact of the Autonomic Nervous System on the Skeleton.Physiological reviews · 2018Review
- Chronological differential effects of pro-inflammatory cytokines on RANKL-induced osteoclast differentiation of canine bone marrow-derived macrophages.The Journal of veterinary medical science · 2017Article
- CB2 cannabinoid receptor agonist enantiomers HU-433 and HU-308: An inverse relationship between binding affinity and biological potency.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Dynamic microglial alterations underlie stress-induced depressive-like behavior and suppressed neurogenesis.Molecular psychiatry · 2014Article
- Skeletal parasympathetic innervation communicates central IL-1 signals regulating bone mass accrual.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- CB2 cannabinoid receptor targets mitogenic Gi protein-cyclin D1 axis in osteoblasts.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2011Article
- Depression, selective serotonin reuptake inhibitors, and osteoporosis.Current osteoporosis reports · 2010Review
- Direct inhibition of human RANK+ osteoclast precursors identifies a homeostatic function of IL-1beta.Journal of immunology (Baltimore, Md. : 1950) · 2010Article
- GPCR kinase 2 interacting protein 1 (GIT1) regulates osteoclast function and bone mass.Journal of cellular physiology · 2010Article
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The proinflammatory cytokine IL-1, acting via the hypothalamic IL-1 receptor type 1 (IL-1RI), activates pathways known to suppress bone formation such as the hypothalamo pituitary-adrenocortical axis and the sympathetic nervous system. In addition, peripheral IL-1 has been implicated as a mediator of the bone loss induced by sex hormone depletion and TNF. Here, we report an unexpected low bone mass (LBM) phenotype, including impairment of bone growth, in IL-1RI-deficient mice (IL-1rKO mice). Targeted overexpression of human IL-1 receptor antagonist to the central nervous system using the murine glial fibrillary acidic protein promoter (IL-1raTG mice) resulted in a similar phenotype, implying that central IL-1RI silencing is the causative process in the LBM induction. Analysis of bone remodeling indicates that the process leading to the LBM in both IL-1rKO and IL-1raTG is characterized mainly by doubling the osteoclast number. Either genetic modification does not decrease testosterone or increase corticosterone serum levels, suggesting that systems other than the gonads and hypothalamo pituitary-adrenocortical axis mediate the central IL-1RI effect on bone. We further demonstrate that WT mice express mouse IL-1ra in bone but not in the hypothalamus. Because low levels of IL-1 are present in both tissues, it is suggested that skeletal IL-1 activity is normally suppressed, whereas central IL-1 produces a constant physiologic stimulation of IL-1RI signaling. Although the pathway connecting the central IL-1RI signaling to bone remodeling remains unknown, the outburst of osteoclastogenesis in its absence suggests that normally it controls bone growth and mass by tonically restraining bone resorption.
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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.