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.

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.

• 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
• Contract Date: Sep 6, 2016