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Chitinase 3-like 1 expression by human (MG63) osteoblasts in response to lysophosphatidic acid and 1,25-dihydroxyvitamin D3

Mansell, J. P.; Mansell, Jason; Cooke, M.; Read, M.; Rudd, H.; Shiel, A. I.; Wilkins, K.; Manso, M.

Chitinase 3-like 1 expression by human (MG63) osteoblasts in response to lysophosphatidic acid and 1,25-dihydroxyvitamin D3 Thumbnail


Authors

J. P. Mansell

Jason Mansell Jason.Mansell@uwe.ac.uk
Associate Professor in Biomedical Sciences

M. Cooke

M. Read

H. Rudd

A. I. Shiel

K. Wilkins

M. Manso



Abstract

© 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM) Chitinase 3-like 1, otherwise known as YKL-40, is a secreted glycoprotein purported to have a role in extracellular matrix metabolism. The first mammalian cell type found to express YKL-40 was the human osteosarcoma-derived osteoblast, MG63. In that first study the active vitamin D3 metabolite, 1,25-dihydroxycholecalciferol (1,25D), stimulated YKL-40 expression, thereby indicating that a vital factor for skeletal health promoted YKL-40 synthesis by bone forming cells. However, when these MG63cells were exposed to 1,25D they were also exposed to serum, a rich source of the pleiotropic lipid mediator, lysophosphatidic acid (LPA). Given that 1,25D is now known to co-operate with selected growth factors, including LPA, to influence human osteoblast differentiation we hypothesised that 1,25D and LPA may work together to stimulate osteoblast YKL-40 expression. Herein we report that 1,25D and LPA synergistically promote YKL-40 expression by MG63cells. Inhibitors targeting AP1, MEK, Sp1 and STAT3 blunted the expression of both alkaline phosphatase and YKL-40 by MG63cells in response to co-stimulation with 1,25D and LPA. Other ligands of the vitamin D receptor also co-operated with LPA in driving YKL-40 mobilisation. Collectively our findings highlight another important role of 1,25D and LPA in the regulation of human osteoblast function.

Citation

Mansell, J. P., Mansell, J., Cooke, M., Read, M., Rudd, H., Shiel, A. I., …Manso, M. (2016). Chitinase 3-like 1 expression by human (MG63) osteoblasts in response to lysophosphatidic acid and 1,25-dihydroxyvitamin D3. Biochimie, 128-129, 193-200. https://doi.org/10.1016/j.biochi.2016.08.011

Journal Article Type Article
Acceptance Date Aug 25, 2016
Online Publication Date Aug 27, 2016
Publication Date Sep 1, 2016
Deposit Date Sep 6, 2016
Publicly Available Date Aug 27, 2017
Journal Biochimie
Print ISSN 0300-9084
Electronic ISSN 6183-1638
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 128-129
Pages 193-200
DOI https://doi.org/10.1016/j.biochi.2016.08.011
Keywords osteoblasts, active vitamin D, lysophosphatidic acid, differentiation, alkaline phosphatase, YKL-40
Public URL https://uwe-repository.worktribe.com/output/908609
Publisher URL http://dx.doi.org/10.1016/j.biochi.2016.08.011

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