Endothelin Signaling in Bone - 15/12/17

Doi : 10.1016/j.ecl.2016.09.014

Jasmin Kristianto, PhD ^a, Michael G. Johnson, PhD ^b, Rafia Afzal, MBBS ^c, Robert D. Blank, MD, PhD ^a,^d,^⁎
^a Divisions of Endocrinology, Metabolism, and Clinical Nutrition, Department of Medicine, Medical College of Wisconsin, 9200 West Wisconsin Avenue, Milwaukee, WI 53226, USA
^b Department of Medicine, University of Wisconsin, 600 Highland Avenue, Madison, WI 53792, USA
^c Department of Anesthesiology, Aga Khan University Hospital, Stadium Road, Karachi 74800, Pakistan
^d Medical Service, Clement J. Zablocki VAMC, 5000 West National Avenue, Milwaukee, WI 53295, USA

^∗Corresponding author. 9200 West Wisconsin Avenue, Milwaukee, WI 53226.9200 West Wisconsin AvenueMilwaukeeWI53226

Résumé

The endothelin (ET) system includes 3 small peptide hormones and a pair of G-protein–coupled receptors. This review first outlines the ET signaling pathway and ET metabolism. Next, it summarizes the role of ET1 signaling in craniofacial development. Then, it discusses observations relating ET signaling to osteoblastic and other osteosclerotic processes in cancer. Finally, it describes recent work in our laboratory that points to endothelin signaling as an upstream mediator of WNT signaling, promoting bone matrix synthesis and mineralization. It concludes with a statement of some remaining gaps in knowledge and proposals for future research.

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Keywords : WNT Signaling, Endothelin 1 signaling, Osteogenesis, Mechanotransduction, Micro-RNA

Plan

Key points

Introduction

Overview of the endothelin signaling pathway

Endothelin 1 signaling in development

Endothelin signaling in osteoblastic metastasis

Endothelin signaling in bone physiology

Future considerations

	Grant Support: This work was supported in part by VA 1I21 RX1440 and American Heart Association grant 15GRNT25700126 to R.D. Blank.
	Disclosure: Dr R.D. Blank is an investigator in a clinical trial sponsored by Novo Nordisk, a consultant for Bristol-Myers Squibb, and a contributor to UpToDate and receives royalties for this work. Drs J. Kristianto, M.G. Johnson, and R. Afzal have nothing to disclose.
	This work was supported in part by SPiRe Award #1I21 RX1440 from the United States Department of Veterans Affairs Rehabilitation Research and Development Service to R.D. Blank. In addition, this material is the result of work supported with resources and the use of facilities at the Geriatrics Research, Education, and Clinical Center at the William S. Middleton Veterans Hospital in Madison, WI. The opinions expressed herein are those of the authors, and do not represent the views of the US government.