ArticleBone research2024
Brain regulates weight bearing bone through PGE2 skeletal interoception: implication of ankle osteoarthritis and pain.
Article in Bone research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 25 citations in OpenAlex.
- The effect of methylene blue infiltrating injection on anal pain after Milligan-Morgan surgery: A randomized controlled clinical study.Medicine · 2026Trial
- The Interaction Between the Central Nervous System and Dental Tissues: Hypothetical Dental Interoception Inferred From Skeletal Interoception.Journal of oral rehabilitation · 2026Review
- The sixth sense of the brain: interoception in organoid study.Bone research · 2026Review
- Hypothalamic prolactin receptorNature communications · 2026Article
- Skeletal interoception regulates joint homeostasis and PGE2-induced pain: implication of disease-modifying treatment.Bone research · 2026Review
- Spatiotemporal immunomodulation with programmable biomaterials to promote musculoskeletal tissue regeneration.Bioactive materials · 2026Review
- The bone-cerebrovascular axis: effects of bone aging on neurovascular dysfunction and neurodegeneration.The Journal of clinical investigation · 2026Review
- Clinical Determinants and Bone Metabolic Correlates of 24-h Urinary PGE2 and PGEM Excretion in Chinese Adults: A Multicenter Cross-Sectional Study.Biomedicines · 2026Article
- SCD1 Regulates Osteoclast Differentiation by Modulating Arachidonic Acid Metabolism and Mitochondrial Homeostasis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Preserved Mandibular Bone Microarchitecture Following Ovariectomy-induced Osteoporosis is Associated with a Specific Fatty Acid Composition in the Rat.Calcified tissue international · 2026Article
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- Neural regulation of bone: from central neural circuits to peripheral innervation of the skeletal stem cell niche.Bone research · 2026Review
- Mechanotransduction and musculoskeletal regeneration: Molecular mechanisms and interdisciplinary applications.Genes & diseases · 2026Review
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- Advances in the regulation of bone metabolism by central nuclei: a new perspective on the brain-bone axis.Frontiers in neuroscience · 2026Review
- The relationship between circulating and tissue biomarkers and OA-related pain: A systematic literature review.Osteoarthritis and cartilage open · 2025Review
- A thermo-sensitive hydrogel targeting macrophage reprogramming for sustained osteoarthritis pain relief.Acta pharmaceutica Sinica. B · 2025Article
- Unraveling the Bone-Brain Communication Network.Biology · 2025Review
- Cross-regulation of inflammation and metabolic mechanisms in osteoarthritis: recent advances bridging the gap to novel treatments.Connective tissue research · 2025Review
- Bone mechanical loading reduces heart rate and increases heart rate variability in mice.Bone reports · 2025Article
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11 authors at 1 institution in 1 country.
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Abstract
Bone is a mechanosensitive tissue and undergoes constant remodeling to adapt to the mechanical loading environment. However, it is unclear whether the signals of bone cells in response to mechanical stress are processed and interpreted in the brain. In this study, we found that the hypothalamus of the brain regulates bone remodeling and structure by perceiving bone prostaglandin E2 (PGE2) concentration in response to mechanical loading. Bone PGE2 levels are in proportion to their weight bearing. When weight bearing changes in the tail-suspension mice, the PGE2 concentrations in bones change in line with their weight bearing changes. Deletion of cyclooxygenase-2 (COX2) in the osteoblast lineage cells or knockout of receptor 4 (EP4) in sensory nerve blunts bone formation in response to mechanical loading. Moreover, knockout of TrkA in sensory nerve also significantly reduces mechanical load-induced bone formation. Moreover, mechanical loading induces cAMP-response element binding protein (CREB) phosphorylation in the hypothalamic arcuate nucleus (ARC) to inhibit sympathetic tyrosine hydroxylase (TH) expression in the paraventricular nucleus (PVN) for osteogenesis. Finally, we show that elevated PGE2 is associated with ankle osteoarthritis (AOA) and pain. Together, our data demonstrate that in response to mechanical loading, skeletal interoception occurs in the form of hypothalamic processing of PGE2-driven peripheral signaling to maintain physiologic bone homeostasis, while chronically elevated PGE2 can be sensed as pain during AOA and implication of potential treatment.
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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.