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 generated many oversized osteoclasts and mineralized poorly compared with wildtype BM. As the CT-1 -/- mice aged, the reduced osteoblast surface (ObS/BS) was no longer detected, but impaired bone resorption continued resulting in an osteopetrotic phenotype in adult bone. CT-1 may now be classed as an essential osteoclast-derived stimulus of both bone formation and resorption.
Original language | English |
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Pages (from-to) | 2025-2032 |
Number of pages | 8 |
Journal | Journal of Bone and Mineral Research |
Volume | 23 |
Issue number | 12 |
DOIs | |
Publication status | Published - 1 Dec 2008 |
Externally published | Yes |
Keywords
- Bone histomorphometry
- Coupling
- Cytokines
- gp130
- Osteoblasts
- Osteoclast