ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2023
Allosteric Activation of Transglutaminase 2 via Inducing an "Open" Conformation for Osteoblast Differentiation.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The trial behind it
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Who cites it
20 citing papers in PubMed, 21 citations in OpenAlex.
- Targeting the gut-bone axis in osteoporosis: probiotic interventions and other microbiota-based therapeutic strategies.Gut microbes · 2026Review
- Targeting eEF1A1 With Baicalein to Block eEF1A1/Prdx4 Interaction for Treating Sepsis-Mediated Lung Injury.Exploration (Beijing, China) · 2026Article
- OV16 Improves Radiation-Induced Intestinal Injury by Targeting Transglutaminase 2.Molecules (Basel, Switzerland) · 2026Article
- Engineered bone-targetingMaterials today. Bio · 2026Article
- Microbial mechanisms and therapeutic interventions in the periodontitis-inflammatory bowel disease axis: a comprehensive review.Journal of oral microbiology · 2026Review
- Targeting G3BP1 Condensate Topology Promotes Stress Granule Assembly via mAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Single-cell RNA-sequencing-guided reactive oxygen species-scavenging hydrogel design for regeneration of osteoporotic bone.Journal of Zhejiang University. Science. B · 2025Article
- Mitochondrial dysfunction in mesenchymal stem cells impairs osteogenesis in radiation-induced bone injury via CaCell death & disease · 2025Article
- Obtain substance of anti-glioblastoma from Erigeron breviscapus through fragment-based target research (FBTR): An efficient strategy for pharmacology investigation and optimization of natural products.Journal of pharmaceutical analysis · 2025Article
- Porphyromonas gingivalis extracellular vesicles exacerbated osteoporosis by disrupting osteoblast mitochondrial dynamics and inhibiting Cpt2-regulated fatty acid oxidation.Journal of nanobiotechnology · 2025Article
- Macrophage response to fibrin structure mediated by Tgm2-dependent mitochondrial mechanosensing.Bioactive materials · 2025Article
- Target discovery-directed pharmacological mechanism elucidation of bioactive natural products.Medical review (2021) · 2025Review
- An emerging role of mitochondrial quality control in bone metabolism: from molecular mechanisms to targeted therapeutic interventions.Cellular and molecular life sciences : CMLS · 2025Review
- Inhibition of Heat Shock Protein 90β by Catalpol: A Potential Therapeutic Approach for Alleviating Inflammation-Induced Cartilage Injuries in Osteoarthritis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Ferulic Acid Combines with Ascorbic Acid to Target MMP9 to Attenuate Cisplatin-Induced Ototoxicity Through the p38MAPK Signaling Pathway.Antioxidants (Basel, Switzerland) · 2025Article
- Canonical and Truncated Transglutaminase-2 Drive TGF-β1 Autocrine Loop to Induce Fibrosis in Graves' Orbitopathy.Investigative ophthalmology & visual science · 2025Article
- Augmentation of bone formation by sympathectomy in rats as evaluated by [Frontiers in endocrinology · 2025Article
- PSO/SDF-1 composite hydrogel promotes osteogenic differentiation of PDLSCs and bone regeneration in periodontitis rats.Heliyon · 2024Article
- Review
- Allosteric Activation of Transglutaminase 2 via Inducing an "Open" Conformation for Osteoblast Differentiation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Osteoblasts play an important role in the regulation of bone homeostasis throughout life. Thus, the damage of osteoblasts can lead to serious skeletal diseases, highlighting the urgent need for novel pharmacological targets. This study introduces chemical genetics strategy by using small molecule forskolin (FSK) as a probe to explore the druggable targets for osteoporosis. Here, this work reveals that transglutaminase 2 (TGM2) served as a major cellular target of FSK to obviously induce osteoblast differentiation. Then, this work identifies a previously undisclosed allosteric site in the catalytic core of TGM2. In particular, FSK formed multiple hydrogen bonds in a saddle-like domain to induce an "open" conformation of the β-sandwich domain in TGM2, thereby promoting the substrate protein crosslinks by incorporating polyamine. Furthermore, this work finds that TGM2 interacted with several mitochondrial homeostasis-associated proteins to improve mitochondrial dynamics and ATP production for osteoblast differentiation. Finally, this work observes that FSK effectively ameliorated osteoporosis in the ovariectomy mice model. Taken together, these findings show a previously undescribed pharmacological allosteric site on TGM2 for osteoporosis treatment, and also provide an available chemical tool for interrogating TGM2 biology and developing bone anabolic agent.
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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.