Imperial College London


Faculty of MedicineNational Heart & Lung Institute

Chair in Cardiology



+44 (0)013 34621727m.d.schneider Website




ICTEM buildingHammersmith Campus






BibTex format

author = {Qi, B and Cong, Q and Li, P and Ma, G and Guo, X and Yeh, J and Xie, M and Schneider, MD and Liu, H and Li, B},
doi = {10.1038/srep07158},
journal = {Scientific Reports},
title = {Ablation of Tak l in osteoclast progenitor leads to defects in skeletal growth and bone remodeling in mice},
url = {},
volume = {4},
year = {2014}

RIS format (EndNote, RefMan)

AB - Tak1 is a MAPKKK that can be activated by growth factors and cytokines such as RANKL and BMPs and its downstream pathways include NF-κB and JNK/p38 MAPKs. Tak1 is essential for mouse embryonic development and plays critical roles in tissue homeostasis. Previous studies have shown that Tak1 is a positive regulator of osteoclast maturation, yet its roles in bone growth and remodeling have not been assessed, as mature osteoclast-specific Tak1 deletion with Cstk-Cre resulted in runtedness and postnatal lethality. Here we generated osteoclast progenitor (monocyte)-specific Tak1 knockout mice and found that these mice show normal body weight, limb size and fertility, and osteopetrosis with severity similar to that of RANK or RANKL deficient mice. Mechanistically, Tak1 deficiency altered the signaling of NF-κB, p38MAPK, and Smad1/5/8 and the expression of PU.1, MITF, c-Fos, and NFATc1, suggesting that Tak1 regulates osteoclast differentiation at multiple stages via multiple signaling pathways. Moreover, the Tak1 mutant mice showed defects in skull, articular cartilage, and mesenchymal stromal cells. Ex vivo Tak1−/− monocytes also showed enhanced ability in promoting osteogenic differentiation of mesenchymal stromal cells. These findings indicate that Tak1 functions in osteoclastogenesis in a cell-autonomous manner and in osteoblastogenesis and chondrogenesis in non-cell-autonomous manners.
AU - Qi,B
AU - Cong,Q
AU - Li,P
AU - Ma,G
AU - Guo,X
AU - Yeh,J
AU - Xie,M
AU - Schneider,MD
AU - Liu,H
AU - Li,B
DO - 10.1038/srep07158
PY - 2014///
SN - 2045-2322
TI - Ablation of Tak l in osteoclast progenitor leads to defects in skeletal growth and bone remodeling in mice
T2 - Scientific Reports
UR -
UR -
VL - 4
ER -