Coordinating Tissue Regeneration Through Transforming Growth Factor-β Activated Kinase 1 Inactivation and Reactivation

Stem Cells
Hsiao Hsin Sung HsiehBenjamin Levi

Abstract

Aberrant wound healing presents as inappropriate or insufficient tissue formation. Using a model of musculoskeletal injury, we demonstrate that loss of transforming growth factor-β activated kinase 1 (TAK1) signaling reduces inappropriate tissue formation (heterotopic ossification) through reduced cellular differentiation. Upon identifying increased proliferation with loss of TAK1 signaling, we considered a regenerative approach to address insufficient tissue production through coordinated inactivation of TAK1 to promote cellular proliferation, followed by reactivation to elicit differentiation and extracellular matrix production. Although the current regenerative medicine paradigm is centered on the effects of drug treatment ("drug on"), the impact of drug withdrawal ("drug off") implicit in these regimens is unknown. Because current TAK1 inhibitors are unable to phenocopy genetic Tak1 loss, we introduce the dual-inducible COmbinational Sequential Inversion ENgineering (COSIEN) mouse model. The COSIEN mouse model, which allows us to study the response to targeted drug treatment ("drug on") and subsequent withdrawal ("drug off") through genetic modification, was used here to inactivate and reactivate Tak1 with the purpose of au...Continue Reading

References

Sep 28, 2005·Nature Immunology·Shintaro SatoShizuo Akira
Nov 26, 2008·Nature Medicine·Paul B YuKenneth D Bloch
Feb 24, 2009·Biochemical and Biophysical Research Communications·Yasumasa MinodaGiichi Takaesu
Jun 19, 2009·The EMBO Journal·Jae-Hyuck ShimLaurie H Glimcher
Mar 10, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Lea M GunnellRegis J O'Keefe
Apr 16, 2010·Annals of the New York Academy of Sciences·Matthew B GreenblattLaurie H Glimcher
Aug 4, 2010·Plastic and Reconstructive Surgery·Benjamin LeviMichael T Longaker
Sep 3, 2010·Plastic and Reconstructive Surgery·Aaron W JamesMichael T Longaker
Mar 16, 2011·Clinical Orthopaedics and Related Research·Lisa A FortierBrian J Cole
Mar 19, 2011·The Journal of Craniofacial Surgery·Benjamin Levi, Michael T Longaker
Apr 17, 2012·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Piyush Koria
May 4, 2012·Science Translational Medicine·Suzanne ZeitouniCarl A Gregory
Nov 22, 2012·Proceedings of the National Academy of Sciences of the United States of America·Benjamin LeviMichael T Longaker
May 29, 2013·Nature Reviews. Rheumatology·Emma Leah
Jun 8, 2013·Nature Medicine·Jason R Bush, Frank Beier
Oct 2, 2013·Proceedings of the National Academy of Sciences of the United States of America·Lissette S VelasquezEric M Small
Jul 19, 2014·The Journal of Clinical Investigation·Everett J ModingDavid G Kirsch
Aug 26, 2014·Cell Death and Differentiation·S R MihalyS Morioka
Sep 26, 2014·Science Translational Medicine·Jonathan R PetersonBenjamin Levi
Oct 4, 2014·Proceedings of the National Academy of Sciences of the United States of America·Yvonne LeungKrzysztof Kobielak
May 11, 2015·Cell Stem Cell·Partha DuttaMatthias Nahrendorf
Jun 5, 2015·Science Translational Medicine·Yong ZhangEllen Heber-Katz
Jul 3, 2015·The Journal of Bone and Joint Surgery. American Volume·Kavitha RanganathanBenjamin Levi
Sep 4, 2015·Science Translational Medicine·Sarah J HatsellAris N Economides
Jan 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Shailesh AgarwalBenjamin Levi
May 11, 2016·Proceedings of the National Academy of Sciences of the United States of America·Xiaochen ZhouYi Sun
Jul 29, 2016·Proceedings of the National Academy of Sciences of the United States of America·Fang ChengJohn E Eriksson
Aug 19, 2016·Science Translational Medicine·Fuqin FanDawang Zhou
Nov 25, 2016·Science Translational Medicine·Devaveena DeyPaul B Yu
Sep 11, 2017·Clinics in Plastic Surgery·Shailesh AgarwalBenjamin Levi

❮ Previous
Next ❯

Citations

Sep 10, 2020·Nature Reviews. Molecular Cell Biology·Ankit SalhotraMichael T Longaker
Jul 28, 2020·International Journal of Molecular Sciences·Nina FrieseAndrea Hoffmann
Feb 20, 2021·Stem Cell Reports·Chase A PaganiBenjamin Levi

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adult Stem Cells

Adult stem cells reside in unique niches that provide vital cues for their survival, self-renewal, and differentiation. They hold great promise for use in tissue repair and regeneration as a novel therapeutic strategies. Here is the latest research.

Allogenic & Autologous Therapies

Allogenic therapies are generated in large batches from unrelated donor tissues such as bone marrow. In contrast, autologous therapies are manufactures as a single lot from the patient being treated. Here is the latest research on allogenic and autologous therapies.

Related Papers

Trends in Pharmacological Sciences
Hiroaki Sakurai
Journal of the Association for Research in Otolaryngology : JARO
Mark A ParkerAlbert S B Edge
Proceedings of the National Academy of Sciences of the United States of America
Hong-Hsing LiuZhijian J Chen
© 2022 Meta ULC. All rights reserved