ArticleNature communications2022
A TrkB agonist prodrug prevents bone loss via inhibiting asparagine endopeptidase and increasing osteoprotegerin.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- 7,8-Dihydroxyflavone ameliorates bone loss by regulating TRKB/AKT/FOXO3a pathway in a mouse model of alzheimer's disease.Psychopharmacology · 2026Article
- Development and validation of a clinical risk stratification model for lumbar vertebral compression fractures in patients with lumbar disc herniation.Bone reports · 2026Article
- C/EBPβ dictates postmenopausal FSHβ transcription and blockade of AEP/C/EBPβ pathway alleviates osteoporosis.Bone research · 2026Article
- MST4 as a key driver of osteoclast activation in osteoporosis.Journal of pharmaceutical analysis · 2026Article
- KCC2 Dysfunction Mediated by Microglial BDNF/TrkB Signaling Exacerbates Early Post-Stroke Seizure Susceptibility.CNS neuroscience & therapeutics · 2026Article
- Steap4 Promotes Senile Osteoporosis via FeAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The therapeutic potential of descending regulatory pathways from brain to bone in osteoporosis: focusing on the brain-bone axis.Frontiers in endocrinology · 2026Review
- Skeletal Muscle as an Auto-, Para- and Endocrine Organ: The Role of Myokines in Muscle Metabolism and Other Metabolic Organs.Physiological research · 2025Review
- The interplay of estrogen, gut microbiome, and bone immunity in osteoporosis.Cell communication and signaling : CCS · 2025Review
- ACE2 Alleviates Microglia Neuroinflammation by RANK-RANKL-OPG Axis in Parkinson's Disease.Inflammation · 2025Article
- Bidirectional Interaction Between the Brain and Bone in Traumatic Brain Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Reduced somatosensory innervation alters the skeletal transcriptome at a single cell level in a mouse model of type 2 diabetes.Bone research · 2025Article
- Targeting the central and peripheral nervous system to regulate bone homeostasis: mechanisms and potential therapies.Military Medical Research · 2025Review
- Asparagine Endopeptidase Inhibition Attenuates Tissue Plasminogen Activator-Induced Brain Hemorrhagic Transformation After Ischemic Stroke.CNS neuroscience & therapeutics · 2025Article
- A Procedural Overview of the Involvement of Small Molecules in the Nervous System in the Regulation of Bone Healing.International journal of nanomedicine · 2025Review
- Roles of myokines in osteoporosis under physiological and diabetic conditions.Frontiers in endocrinology · 2025Review
- Article
- Role of the Neurologic System in Fracture Healing: An Extensive Review.Current osteoporosis reports · 2024Review
- Cracking the Code: The Role of Peripheral Nervous System Signaling in Fracture Repair.Current osteoporosis reports · 2024Review
- Do Not Lose Your Nerve, Be Callus: Insights Into Neural Regulation of Fracture Healing.Current osteoporosis reports · 2024Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Brain-derived neurotrophic factor (BDNF) and its tropomyosin-related kinase B receptor (TrkB) are expressed in human osteoblasts and mediate fracture healing. BDNF/TrkB signaling activates Akt that phosphorylates and inhibits asparagine endopeptidase (AEP), which regulates the differentiation fate of human bone marrow stromal cells (hBMSC) and is altered in postmenopausal osteoporosis. Here we show that R13, a small molecular TrkB receptor agonist prodrug, inhibits AEP and promotes bone formation. Though both receptor activator of nuclear factor kappa-Β ligand (RANK-L) and osteoprotegerin (OPG) induced by ovariectomy (OVX) remain comparable between WT and BDNF+/- mice, R13 treatment significantly elevates OPG in both mice without altering RANKL, blocking trabecular bone loss. Strikingly, both R13 and anti-RANK-L exhibit equivalent therapeutic efficacy. Moreover, OVX increases RANK-L and OPG in WT and AEP KO mice with RANK-L/OPG ratio lower in the latter than the former, attenuating bone turnover. 7,8-DHF, released from R13, activates TrkB and its downstream effector CREB, which is critical for OPG augmentation. Consequently, 7,8-DHF represses C/EBPβ/AEP pathway, inhibiting RANK-L-induced RAW264.7 osteoclastogenesis. Therefore, our findings support that R13 exerts its therapeutic efficacy toward osteoporosis via inhibiting AEP and escalating OPG.
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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.