Matches in SemOpenAlex for { <https://semopenalex.org/work/W4366782417> ?p ?o ?g. }
- W4366782417 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." @default.
- W4366782417 created "2023-04-25" @default.
- W4366782417 creator A5005422339 @default.
- W4366782417 creator A5006012404 @default.
- W4366782417 creator A5013437001 @default.
- W4366782417 creator A5013473523 @default.
- W4366782417 creator A5016145254 @default.
- W4366782417 creator A5017050791 @default.
- W4366782417 creator A5028009429 @default.
- W4366782417 creator A5033469424 @default.
- W4366782417 creator A5034874334 @default.
- W4366782417 creator A5036321004 @default.
- W4366782417 creator A5044129086 @default.
- W4366782417 creator A5076863688 @default.
- W4366782417 creator A5078699661 @default.
- W4366782417 date "2023-04-23" @default.
- W4366782417 modified "2023-10-18" @default.
- W4366782417 title "Allosteric Activation of Transglutaminase 2 via Inducing an “Open” Conformation for Osteoblast Differentiation" @default.
- W4366782417 cites W1594526962 @default.
- W4366782417 cites W1965896502 @default.
- W4366782417 cites W1975740366 @default.
- W4366782417 cites W1984957160 @default.
- W4366782417 cites W1993251792 @default.
- W4366782417 cites W2000834795 @default.
- W4366782417 cites W2009213090 @default.
- W4366782417 cites W2009291798 @default.
- W4366782417 cites W2015779044 @default.
- W4366782417 cites W2019196925 @default.
- W4366782417 cites W2028105165 @default.
- W4366782417 cites W2031883266 @default.
- W4366782417 cites W2070719504 @default.
- W4366782417 cites W2081525068 @default.
- W4366782417 cites W2104675030 @default.
- W4366782417 cites W2110928159 @default.
- W4366782417 cites W2123346255 @default.
- W4366782417 cites W2142410730 @default.
- W4366782417 cites W2143794875 @default.
- W4366782417 cites W2147667459 @default.
- W4366782417 cites W2150137555 @default.
- W4366782417 cites W2169389686 @default.
- W4366782417 cites W2267988149 @default.
- W4366782417 cites W2295351013 @default.
- W4366782417 cites W2507601657 @default.
- W4366782417 cites W2531502250 @default.
- W4366782417 cites W2604145475 @default.
- W4366782417 cites W2605638975 @default.
- W4366782417 cites W2610405998 @default.
- W4366782417 cites W2726318071 @default.
- W4366782417 cites W2746496668 @default.
- W4366782417 cites W2753622751 @default.
- W4366782417 cites W2756212562 @default.
- W4366782417 cites W2770727092 @default.
- W4366782417 cites W2782529520 @default.
- W4366782417 cites W2786620202 @default.
- W4366782417 cites W2795677294 @default.
- W4366782417 cites W2805221036 @default.
- W4366782417 cites W2808816097 @default.
- W4366782417 cites W2907890950 @default.
- W4366782417 cites W2914405566 @default.
- W4366782417 cites W2925284108 @default.
- W4366782417 cites W2993259396 @default.
- W4366782417 cites W2997353369 @default.
- W4366782417 cites W3008307436 @default.
- W4366782417 cites W3027138993 @default.
- W4366782417 cites W3046622411 @default.
- W4366782417 cites W3083952170 @default.
- W4366782417 cites W3107055421 @default.
- W4366782417 cites W3111373006 @default.
- W4366782417 cites W3122577894 @default.
- W4366782417 cites W3156782050 @default.
- W4366782417 cites W3172011806 @default.
- W4366782417 cites W3202456313 @default.
- W4366782417 cites W3215797498 @default.
- W4366782417 cites W4206199438 @default.
- W4366782417 cites W4232487434 @default.
- W4366782417 cites W4237593632 @default.
- W4366782417 cites W4311291416 @default.
- W4366782417 cites W4366782417 @default.
- W4366782417 doi "https://doi.org/10.1002/advs.202206533" @default.
- W4366782417 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37088726" @default.
- W4366782417 hasPublicationYear "2023" @default.
- W4366782417 type Work @default.
- W4366782417 citedByCount "1" @default.
- W4366782417 countsByYear W43667824172023 @default.
- W4366782417 crossrefType "journal-article" @default.
- W4366782417 hasAuthorship W4366782417A5005422339 @default.
- W4366782417 hasAuthorship W4366782417A5006012404 @default.
- W4366782417 hasAuthorship W4366782417A5013437001 @default.
- W4366782417 hasAuthorship W4366782417A5013473523 @default.
- W4366782417 hasAuthorship W4366782417A5016145254 @default.
- W4366782417 hasAuthorship W4366782417A5017050791 @default.
- W4366782417 hasAuthorship W4366782417A5028009429 @default.
- W4366782417 hasAuthorship W4366782417A5033469424 @default.
- W4366782417 hasAuthorship W4366782417A5034874334 @default.
- W4366782417 hasAuthorship W4366782417A5036321004 @default.
- W4366782417 hasAuthorship W4366782417A5044129086 @default.
- W4366782417 hasAuthorship W4366782417A5076863688 @default.
- W4366782417 hasAuthorship W4366782417A5078699661 @default.
- W4366782417 hasBestOaLocation W43667824171 @default.
- W4366782417 hasConcept C161624437 @default.