Legumain Regulates Differentiation Fate of Human Bone Marrow Stromal Cells and Is Altered in Postmenopausal Osteoporosis

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2017 Feb 7

PMID 28162997

Citations 38

Authors

Abbas Jafari

Diyako Qanie

Thomas L Andersen

Yuxi Zhang

Li Chen

Benno Postert

Stuart Parsons

Nicholas Ditzel

Sundeep Khosla

Harald Thidemann Johansen

Per Kjaersgaard-Andersen

Jean-Marie Delaisse

Basem M Abdallah

Daniel Hesselson

Rigmor Solberg

Moustapha Kassem

Affiliations

Soon will be listed here.

Abstract

Secreted factors are a key component of stem cell niche and their dysregulation compromises stem cell function. Legumain is a secreted cysteine protease involved in diverse biological processes. Here, we demonstrate that legumain regulates lineage commitment of human bone marrow stromal cells and that its expression level and cellular localization are altered in postmenopausal osteoporotic patients. As shown by genetic and pharmacological manipulation, legumain inhibited osteoblast (OB) differentiation and in vivo bone formation through degradation of the bone matrix protein fibronectin. In addition, genetic ablation or pharmacological inhibition of legumain activity led to precocious OB differentiation and increased vertebral mineralization in zebrafish. Finally, we show that localized increased expression of legumain in bone marrow adipocytes was inversely correlated with adjacent trabecular bone mass in a cohort of patients with postmenopausal osteoporosis. Our data suggest that altered proteolytic activity of legumain in the bone microenvironment contributes to decreased bone mass in postmenopausal osteoporosis.

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