Skip to main content

Research Repository

Advanced Search

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.


J. P. Mansell

Jason Mansell
Associate Professor in Biomedical Sciences

M. Cooke

M. Read

H. Rudd

A. I. Shiel

K. Wilkins

M. Manso


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 MG63 cells 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 MG63 cells. Inhibitors targeting AP1, MEK, Sp1 and STAT3 blunted the expression of both alkaline phosphatase and YKL-40 by MG63 cells 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.


Mansell, J., Cooke, M., Read, M., Rudd, H., Shiel, A., Wilkins, K., & Manso, M. (2016). Chitinase 3-like 1 expression by human (MG63) osteoblasts in response to lysophosphatidic acid and 1,25-Dihydroxyvitamin D3. Biochimie, 128-9, 193-200.

Journal Article Type Article
Acceptance Date Aug 25, 2016
Online Publication Date Aug 27, 2016
Publication Date Sep 1, 2016
Journal Biochimie
Print ISSN 0300-9084
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 128-9
Pages 193-200
Keywords osteoblasts, active vitamin D, lysophosphatidic acid, differentiation, alkaline phosphatase, YKL-40
Public URL
Publisher URL


You might also like

Downloadable Citations