ArticleCell death & disease2019
Tetrandrine enhances the ubiquitination and degradation of Syk through an AhR-c-src-c-Cbl pathway and consequently inhibits osteoclastogenesis and bone destruction in arthritis.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- Review
- Aryl hydrocarbon receptor impairs HK2-controlled flux of the hexosamine biosynthesis pathway to suppress NETosis in an N-glycosylation-dependent manner.Journal of advanced research · 2026Article
- Reimagining AHR in Cancer: From Environmental Sensor to Novel Immunomodulatory Therapeutic Target.International journal of biological sciences · 2026Review
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- Expression of the aryl hydrocarbon receptor in Osterix-lineage cells regulates adult skeletal homeostasis in a compartment-specific manner.JBMR plus · 2025Article
- The role of the AHR in host-pathogen interactions.Nature reviews. Immunology · 2025Review
- Aberrant Tryptophan Metabolism Manipulates Osteochondral Homeostasis.Research (Washington, D.C.) · 2025Review
- Lignans-rich extract ofCurrent research in food science · 2025Article
- Article
- Review
- The Role of Aryl Hydrocarbon Receptor in Bone Biology.International journal of tryptophan research : IJTR · 2024Review
- Article
- Tetrandrine Represses Inflammation and Attenuates Osteoarthritis by Selective Inhibition of COX-2.Current medical science · 2023Article
- Cholinergic dysfunction-induced insufficient activation of alpha7 nicotinic acetylcholine receptor drives the development of rheumatoid arthritis through promoting protein citrullinationActa pharmaceutica Sinica. B · 2023Article
- Functions of the aryl hydrocarbon receptor (AHR) beyond the canonical AHR/ARNT signaling pathway.Biochemical pharmacology · 2023Review
- Tetrandrine alleviates inflammation and neuron apoptosis in experimental traumatic brain injury by regulating the IRE1α/JNK/CHOP signal pathway.Brain and behavior · 2022Article
- Aryl hydrocarbon receptor (AhR)-mediated signaling as a critical regulator of skeletal cell biology.Journal of molecular endocrinology · 2022Review
- Natural medicines of targeted rheumatoid arthritis and its action mechanism.Frontiers in immunology · 2022Review
- Tetrandrine Ameliorates Rheumatoid Arthritis in Mice by Alleviating Neutrophil Activities.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- The bone-protective mechanisms of active components from TCM drugs in rheumatoid arthritis treatment.Frontiers in pharmacology · 2022Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, we reported that tetrandrine, a natural alkaloid, could inhibit the osteoclastogenesis and bone erosion through enhancing the ubiquitination and degradation of spleen tyrosine kinase (Syk). Herein, we addressed whether and how aryl hydrocarbon receptor (AhR) mediate the effect of tetrandrine. In vitro, tetrandrine was shown to repress RANKL-induced osteoclastogenesis and the expression of osteoclast-related marker genes, which was almost completely reversed by either AhR antagonist CH223191 or siRNA. In pre-osteoclasts, tetrandrine enhanced the ubiquitination and degradation of Syk through the AhR/c-src/c-Cbl signaling pathway, downregulated the expression of phospho-Syk and phospho-PLCγ2, and inhibited the nuclear translocation of NFATc1, a master transcription factor for osteoclastogenesis. Notably, tetrandrine acted through the non-genomic pathway of the ligand-activated AhR, as evidenced by the fact that the effect of tetrandrine did not change in the absence of AhR nuclear translocator. In collagen-induced arthritis rats, oral administration of tetrandrine decreased the number of phospho-Syk-positive cells and osteoclasts, and reduced the bone erosion in the areas of the proximal tibial epiphysis excluding the cortical bone. A combined use with CH223191 almost abolished the effect of tetrandrine. These findings revealed that tetrandrine enhanced the ubiquitination and degradation of Syk and consequently repressed the osteoclastogenesis and bone destruction through the AhR-c-src-c-Cbl pathway.
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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.