ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2010
TAK1 regulates cartilage and joint development via the MAPK and BMP signaling pathways.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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63 citing papers in PubMed, 91 citations in OpenAlex.
- Review
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- Poly-(D,L)-Lactide-ε-Caprolactone-Methacrylate Is a Suitable Scaffold Material for In Vitro Cartilage Regeneration.International journal of molecular sciences · 2025Article
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- PDGFRα signaling regulates cartilage and fibrous tissue differentiation during synovial joint development.Nature communications · 2025Article
- Tgfβ signaling stimulates glycolysis to promote the genesis of synovial joint interzone in developing mouse embryonic limbs.Science advances · 2025Article
- Effects of selenium-mediated RUNX2 overexpression and its transcriptome alterations on Chondrocyte injury in Kashin Beck disease.Frontiers in cell and developmental biology · 2025Article
- Role of the NF-kB signalling pathway in heterotopic ossification: biological and therapeutic significance.Cell communication and signaling : CCS · 2024Review
- The roles and regulatory mechanisms of TGF-β and BMP signaling in bone and cartilage development, homeostasis and disease.Cell research · 2024Review
- Application of dental pulp stem cells for bone regeneration.Frontiers in medicine · 2024Review
- LncRNA-mediated cartilage homeostasis in osteoarthritis: a narrative review.Frontiers in medicine · 2024Review
- Transforming growth factor-β and bone morphogenetic protein signaling pathways in pathological cardiac hypertrophy.Cell cycle (Georgetown, Tex.) · 2023Review
- Engineering Inflammation-Resistant Cartilage: Bridging Gene Therapy and Tissue Engineering.Advanced healthcare materials · 2023Article
- The role of TGF-beta3 in cartilage development and osteoarthritis.Bone research · 2023Review
- The context-dependent, combinatorial logic of BMP signaling.Cell systems · 2022Article
- GCN5-mediated regulation of pathological cardiac hypertrophy via activation of the TAK1-JNK/p38 signaling pathway.Cell death & disease · 2022Article
- Integrated regulation of chondrogenic differentiation in mesenchymal stem cells and differentiation of cancer cells.Cancer cell international · 2022Review
- An integrative analysis of DNA methylation and transcriptome showed the dysfunction of MAPK pathway was involved in the damage of human chondrocyte induced by T-2 toxin.BMC molecular and cell biology · 2022Article
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3 more citing papers are in PubMed but not listed here.
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7 authors at 1 institution in 1 country.
Funding
Abstract
The importance of canonical transforming growth factor beta (TGF-beta) and bone morphogenetic protein (BMP) signaling during cartilage and joint development is well established, but the necessity for noncanonical (SMAD-independent) signaling during these processes is largely unknown. TGF-beta activated kinase 1 (TAK1) is a MAP3K activated by TGF-beta, BMP, and other mitogen-activated protein kinase (MAPK) signaling components. We set out to define the potential role for noncanonical, TAK1-mediated signaling in cartilage and joint development via deletion of Tak1 in chondrocytes (Col2Cre;Tak1(f/f)) and the developing limb mesenchyme (Prx1Cre;Tak1(f/f)). Deletion of Tak1 in chondrocytes resulted in novel embryonic developmental cartilage defects including decreased chondrocyte proliferation, reduced proliferating chondrocyte survival, delayed onset of hypertrophy, reduced Mmp13 expression, and a failure to maintain interzone cells of the elbow joint, which were not observed previously in another Col2Cre;Tak1(f/f) model. Deletion of Tak1 in limb mesenchyme resulted in widespread joint fusions likely owing to the differentiation of interzone cells to the chondrocyte lineage. The Prx1Cre;Tak1(f/f) model also allowed us to identify novel columnar chondrocyte organization and terminal maturation defects owing to the interplay between chondrocytes and the surrounding mesenchyme. Furthermore, both our in vivo models and in vitro cell culture studies demonstrate that loss of Tak1 results in impaired activation of the downstream MAPK target p38, as well as diminished activation of the BMP/SMAD signaling pathway. Taken together, these data demonstrate that TAK1 is a critical regulator of both MAPK and BMP signaling and is necessary for proper cartilage and joint development.
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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.