Cited by 190Bone Metabolism and DiseasesBone health and osteoporosis researchAlkaline Phosphatase Research Studies

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Cardiotrophin-1 Is an Osteoclast-Derived Stimulus of Bone Formation Required for Normal Bone Remodeling

Walker, Emma C, McGregor, Narelle E, Poulton, Ingrid J, Pompolo, Sueli, Allan, Elizabeth H, Quinn, Julian MW, Gillespie, Matthew T, Martin, T John, Sims, Natalie A·2008·Journal of Bone and Mineral Research

DOI 10.1359/jbmr.080706

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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.

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Authors: Walker, E. C., McGregor, N. E., Poulton, I. J., Pompolo, S., Allan, E. H., Quinn, J. M., Gillespie, M. T., Martin, T. J., & Sims, N. A.
Affiliations: St Vincents Institute of Medical Research (AU)
The University of Melbourne (AU)
Corresponding author: Sims, Natalie A
ORCID: Walker, Emma C
Gillespie, Matthew T
Martin, T John
Sims, Natalie A
Venue: Journal of Bone and Mineral Research
Publisher: Oxford University Press (OUP)
Published: 2008-12-01
Volume: 23
Issue: 12
Pages: 2025-2032
ISSN: 0884-0431 (ISSN-L)
1523-4681
DOI: 10.1359/jbmr.080706
OpenAlex: W2044726772
Cited by: 190
References: 40
Citations by year: 2026: 6 · 2025: 4 · 2024: 10 · 2023: 1 · 2022: 12 · 2021: 16 · 2020: 19 · 2019: 11 · 2018: 8 · 2017: 14 · 2016: 6 · 2015: 13 · 2014: 16 · 2013: 8 · 2012: 15
FWCI: 4.25
Type: journal article
Language: en
Open access: closed
Licence: academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations: Journal of Bone and Mineral Research (publishedVersion)
PubMed (publishedVersion)
Funders: National Health and Medical Research Council
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
Keywords: cardiotrophin-1, osteoclasts, bone remodeling, bone formation, bone resorption, osteoblast activity, mineralization, C/EBPδ, Runx2, gp130, LIF receptor, osteopenia, bone marrow
MeSH terms: Animals, Bone and Bones, Bone Marrow, Bone Resorption, Female, Male, Mice, Inbred C57BL, Mice, Transgenic, Osteoblasts, Osteoclasts, Transcription Factors, Cytokines, Bone Remodeling, Mice, CCAAT-Enhancer-Binding Protein-delta

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Cardiotrophin-1 Is an Osteoclast-Derived Stimulus of Bone Formation Required for Normal Bone Remodeling

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