ArticleCell death & disease2018
Osteocalcin triggers Fas/FasL-mediated necroptosis in adipocytes via activation of p300.
Article in Cell death & disease, 2018. 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, 51 citations in OpenAlex.
- Biomaterials at the interface of bone-derived factors and inter-organ communication: Current evidence and future perspectives.Bioactive materials · 2026Review
- Nano-formulations in therapeutic strategies targeting cancer ferroptosis.Journal of pharmaceutical analysis · 2026Review
- Keratin 18 functions as a lactyltransferase to trigger necroptosis in diabetic kidney disease by modulating Fas transcription.Experimental & molecular medicine · 2026Article
- The role and mechanism of TNFRSF21 in promoting necroptosis of vascular endothelial cells and inducing vascular leakage in sepsis.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Advances inMicroorganisms · 2025Review
- How transcription factors regulate apoptosis in endometriosis (Review).Molecular medicine reports · 2025Review
- Transcriptional remodeling shapes therapeutic vulnerability to necroptosis in acute lymphoblastic leukemia.Blood · 2025Article
- ERK1/2 Signaling in Intrahepatic Cholangiocarcinoma: From Preclinical Advances to Therapeutic Strategies.Biology · 2025Review
- An Overview of Hexavalent Chromium-Induced Necroptosis, Pyroptosis, and Ferroptosis.Biological trace element research · 2025Review
- Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs.Bone research · 2025Review
- Transcriptomic and Lipidomic Characteristics of Subcutaneous Fat Deposition in Small-Sized Meat Ducks.Metabolites · 2025Article
- Electroacupuncture Mitigates TRPV1 Overexpression in the Central Nervous System Associated with Fibromyalgia in Mice.Life (Basel, Switzerland) · 2024Article
- Induced Necroptosis and Its Role in Cancer Immunotherapy.International journal of molecular sciences · 2024Review
- Osteocalcin: Beyond Bones.Endocrinology and metabolism (Seoul, Korea) · 2024Review
- Targeting P2YNature communications · 2024Article
- Crosstalk between Lipid Metabolism and Bone Homeostasis: Exploring Intricate Signaling Relationships.Research (Washington, D.C.) · 2024Article
- The role of pyroptosis and gasdermin family in tumor progression and immune microenvironment.Experimental hematology & oncology · 2023Review
- Comparison of the Ways in Which Nitidine Chloride and Bufalin Induce Programmed Cell Death in Hematological Tumor Cells.Applied biochemistry and biotechnology · 2023Article
- Deficiency of salt-inducible kinase 2 (SIK2) promotes immune injury by inhibiting the maturation of lymphocytes.MedComm · 2023Article
- Mechanism of ERK/CREB pathway in pain and analgesia.Frontiers in molecular neuroscience · 2023Review
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The uncarboxylated form of osteocalcin (GluOC) regulates glucose and lipid metabolism in mice. We previously showed that low-dose (≤10 ng/ml) GluOC induces the expression of adiponectin and peroxisome proliferator-activated receptor γ (PPARγ) via a cAMP-PKA-ERK-CREB signaling pathway in 3T3-L1 adipocytes. We also noticed that high-dose (≥20 ng/ml) GluOC inhibits the expression of adiponectin and PPARγ in these cells. We have here explored the mechanism underlying these effects of high-dose GluOC. High-dose GluOC triggered morphological changes in 3T3-L1 adipocytes suggestive of the induction of cell death. It activated the putative GluOC receptor GPRC6A and thereby induced the production of cAMP and activation of protein kinase A (PKA), similar to signaling by low-dose GluOC with the exception that the catalytic subunit of PKA also entered the nucleus. Cytosolic PKA induced phosphorylation of cAMP response element-binding protein (CREB) at serine-133 via extracellular signal-regulated kinase (ERK). Nuclear PKA appeared to mediate the inhibitory phosphorylation of salt-inducible kinase 2 (SIK2) at serine-358 and thereby to alleviate the inhibitory phosphorylation of the CREB co-activator p300 at serine-89. The activation of CREB and p300 resulted in increased expression of the transcription factor FoxO1 and consequent upregulation of Fas ligand (FasL) at the plasma membrane. The interaction of FasL with Fas on neighboring adipocytes triggered the phosphorylation at threonine-357/serine-358 and homotrimerization of mixed-lineage kinase domain-like protein (MLKL), a key regulator of necroptosis, as well as Ca
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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.