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Bone. 2018 Jul;112:120-127. doi: 10.1016/j.bone.2018.04.015. Epub 2018 Apr 19.

IL-6 trans-signalling mediates trabecular, but not cortical, bone loss after ovariectomy.

Author information

1
St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia; The University of Melbourne, Department of Medicine at St. Vincent's Hospital, Fitzroy, Victoria, Australia.
2
St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia.
3
NovImmune SA, Geneva, Switzerland.
4
St. Vincent's Institute of Medical Research, Fitzroy, Victoria, Australia; The University of Melbourne, Department of Medicine at St. Vincent's Hospital, Fitzroy, Victoria, Australia. Electronic address: nsims@svi.edu.au.

Abstract

Bone loss associated with estrogen deficiency occurs due to a high level of bone remodelling, with a greater increase in the level of osteoclast-mediated bone resorption than osteoblast-mediated bone formation. Early studies showed that Interleukin-6 (IL-6) inhibition could prevent the increase in osteoclast numbers associated with ovariectomy. However, IL-6 signals through two possible pathways: classic IL-6 signalling (cis) utilizes a membrane-bound IL-6 receptor (IL-6R), while IL-6 trans-signalling occurs through a soluble IL-6R (sIL-6R). It is not known which of these pathways mediates the bone loss after ovariectomy. We therefore sought to determine whether specific pharmacological inhibition of IL-6 trans-signalling could prevent ovariectomy-induced bone loss in mice. We report that IL-6 trans-signalling inhibition prevented the increase in osteoclasts, and trabecular bone loss, associated with ovariectomy. IL-6 trans-signalling inhibition also reduced bone formation rate, but did not prevent the increase in osteoblast numbers. In contrast, cortical bone loss was not prevented by any IL-6 signalling inhibitor. This suggests that local production of sIL-6R mediates trabecular bone loss in estrogen deficiency, but the increased cortical bone resorption that leads to marrow expansion is independent of IL-6 signalling.

KEYWORDS:

Cytokines; Histomorphometry; IL-6; Ovariectomy; cortical bone; gp130; osteoclast

PMID:
29679733
DOI:
10.1016/j.bone.2018.04.015
[Indexed for MEDLINE]

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