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Ciliary Neurotrophic Factor Inhibits Bone Formation and Plays a Sex-Specific Role in Bone Growth and Remodeling

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An Erratum to this article was published on 15 March 2013

Abstract

Ciliary neurotrophic factor (CNTF) receptor (CNTFR) expression has been described in osteoblast-like cells, suggesting a role for CNTF in bone metabolism. When bound to CNTF, neuropoietin (NP), or cardiotrophin-like-cytokine (CLC), CNTFR forms a signaling complex with gp130 and the leukemia inhibitory factor receptor, which both play critical roles in bone cell biology. This study aimed to determine the role of CNTFR-signaling cytokines in bone. Immunohistochemistry detected CNTF in osteoblasts, osteocytes, osteoclasts, and proliferating chondrocytes. CNTFR mRNA was detected in primary calvarial osteoblasts and was upregulated during osteoblast differentiation. Treatment of osteoblasts with CNTF or CLC, but not NP, significantly inhibited mineralization and osterix mRNA levels. Twelve-week-old male CNTF −/− mice demonstrated reduced femoral length, cortical thickness, and periosteal circumference; but femoral trabecular bone mineral density (Tb.BMD) and tibial trabecular bone volume (BV/TV) were not significantly different from wild-type, indicating a unique role for CNTF in bone growth in male mice. In contrast, female CNTF −/− femora were of normal width, but femoral Tb.BMD, tibial BV/TV, trabecular number, and trabecular thickness were all increased. Female CNTF −/− tibiae also demonstrated high osteoblast number and mineral apposition rate compared to wild-type littermates, and this was intrinsic to the osteoblast lineage. CNTF is expressed locally in bone and plays a unique role in female mice as an inhibitor of trabecular bone formation and in male mice as a stimulus of cortical growth.

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Acknowledgements

We thank Dr. John Wark and Ms. Susan Kantor at the Department of Medicine, Royal Melbourne Hospital, for use of pQCT and Dr. Bettina Holtmann and Prof. Michael Sendtner, University of Würzburg, for providing CNTF −/− mice. 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 N. A. S. and T. J. M.). N. A. S. is supported by an NHMRC (Australia) Senior Research Fellowship.

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  1. Julian M. W. Quinn

    Present address: Monash Medical Centre, Prince Henry’s Institute, Level 4, Block E, 246 Clayton Road, Clayton, VIC, 3168, Australia

Authors and Affiliations

  1. St. Vincent’s Institute, 9 Princes Street, Fitzroy, VIC, 3065, Australia

    Narelle E. McGregor, Ingrid J. Poulton, Emma C. Walker, Sueli Pompolo, Julian M. W. Quinn, T. John Martin & Natalie A. Sims

  2. Department of Medicine, St. Vincent’s Hospital, The University of Melbourne, Fitzroy, VIC, 3065, Australia

    Julian M. W. Quinn, T. John Martin & Natalie A. Sims

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  1. Narelle E. McGregor
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Correspondence to Natalie A. Sims.

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The authors have stated that they have no conflict of interest.

An erratum to this article can be found online at http://dx.doi.org/10.1007/s00223-013-9719-5.

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McGregor, N.E., Poulton, I.J., Walker, E.C. et al. Ciliary Neurotrophic Factor Inhibits Bone Formation and Plays a Sex-Specific Role in Bone Growth and Remodeling. Calcif Tissue Int 86, 261–270 (2010). https://doi.org/10.1007/s00223-010-9337-4

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