Suppressor of cytokine signaling 2 (Socs2) deletion protects bone health of mice with DSS-induced inflammatory bowel disease

Dobie, R., MacRae, V.E., Pass, C., Milne, E.M. and Ahmed, S.F. (2018) Suppressor of cytokine signaling 2 (Socs2) deletion protects bone health of mice with DSS-induced inflammatory bowel disease. Disease Models and Mechanisms, 11(1), dmm028456. (doi: 10.1242/dmm.028456) (PMID:29343614) (PMCID:PMC5818069)

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Individuals with inflammatory bowel disease (IBD) often present with poor bone health. The development of targeted therapies for this bone loss requires a fuller understanding of the underlying cellular mechanisms. Although bone loss in IBD is multifactorial the altered sensitivity and secretion of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) in IBD is understood to be a critical contributing mechanism. The expression of suppressor of cytokine signaling 2 (SOCS2), a well-established negative regulator of GH signaling, is stimulated by pro-inflammatory cytokines. Therefore, it is likely that SOCS2 expression represents a critical mediator through which pro-inflammatory cytokines inhibit GH/IGF-1 signaling and decrease bone quality in IBD. Utilising the DSS model of colitis we have revealed that endogenously elevated GH function in the Socs2−/− mouse protects the skeleton from osteopenia. Micro-computed tomography assessment of DSS treated wild-type mice revealed a worsened trabecular architecture compared to control mice. Specifically, DSS treated WT mice had significantly decreased bone volume (BV/TV) (41%; p<0.05), trabecular thickness (16%; p<0.05), trabecular number (30%; p<0.05), and a resulting increase in trabecular separation (19%; <0.05). In comparison, the trabecular bone of Socs2 deficient mice was partially protected from the adverse effects of DSS. The reduction in a number of parameters including BV/TV (21%; p<0.05) was less, and no changes were observed in trabecular thickness or separation. This protected phenotype was unlikely to be a consequence of improved mucosal health in the DSS treated Socs2−/− mice but rather a result of unregulated GH signaling directly on bone. These studies indicate that the absence of SOCS2 is protective against bone loss typical of IBD. This study also provides an improved understanding of the relative effects of GH/IGF-1 on bone health in experimental colitis, information that is essential before these drugs are explored as bone protective agents in children and adults with IBD.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Ahmed, Professor Syed Faisal
Authors: Dobie, R., MacRae, V.E., Pass, C., Milne, E.M., and Ahmed, S.F.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Disease Models and Mechanisms
Publisher:Company of Biologists
ISSN (Online):1754-8411
Published Online:22 December 2017
Copyright Holders:Copyright © 2017 The Company of Biologists Ltd.
First Published:First published in Disease Models and Mechanisms 11(1): dmm028456
Publisher Policy:Reproduced under a Creative Commons License

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