Journal article
Cardiotrophin-1 is an osteoclast-derived stimulus of bone formation required for normal bone remodeling
EC Walker, NE McGregor, IJ Poulton, S Pompolo, EH Allan, JMW Quinn, MT Gillespie, TJ Martin, NA Sims
Journal of Bone and Mineral Research | WILEY | Published : 2008
DOI: 10.1359/jbmr.080706
Abstract
Cardiotrophin (CT-1) signals through gp130 and the LIF receptor (LIFR) and plays a major role in cardiac, neurological, and liver biology. We report here that CT-1 is also expressed within bone in osteoclasts and that CT-1 is capable of increasing osteoblast activity and mineralization both in vitro and in vivo. Furthermore, CT-1 stimulated CAAT/enhancer-binding protein-δ (C/EBPδ) expression and runt-related transcription factor 2 (runx2) activation. In neonate CT-1-/- mice, we detected low bone mass associated with reduced osteoblasts and many large osteoclasts, but increased cartilage remnants within the bone, suggesting impaired resorption. Cultured bone marrow (BM) from CT-1-/- mice gene..
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Awarded by NHMRC (Australia) Program
Funding Acknowledgements
The authors thank Dr John Wark and Susan Kantor at Department of Medicine, Royal Melbourne Hospital, for use of pQCT, Dr Bettina Holtmann and Prof Michael Sendtner, University of Wurzburg, for CT-1<SUP>-/-</SUP> mice, and Prof Gerard Karsenty, Columbia University, for the 6xOSE2 construct. We also thank staff at the Bioresources Centre, St Vincent's Health for excellent animal care. The work was supported by NHMRC (Australia) Program Grant 345401 to NAS, MTG, and TJM. NAS is supported by a NHMRC (Australia) Senior Research Fellowship.