Scavenger receptor class B, type I (Scarb1) deficiency promotes osteoblastogenesis but stunts terminal osteocyte differentiation

Physiological Reports

Corine Martineau²  Olha Kevorkova²  Louise Brissette¹ 

[1] Laboratoire du Métabolisme des Lipoprotéines, BioMed, Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Quebec, Canada;Laboratoire du Métabolisme Osseux, BioMed, Département des Sciences Biologiques, Université du Québec à Montréal, Montréal, Quebec, Canada

关键词: Differentiation;    HDL;    MSC;    osteoblast;    osteocyte;    proliferation;    SR‐BI;    Wnt pathway;   

DOI  :  10.14814/phy2.12117

来源: Wiley

【 摘 要 】

Abstract

Scavenger receptor class B type I (SR-BI), the Scarb1 gene product, is a high-density lipoprotein (HDL) receptor which was shown to influence bone metabolism. Its absence in mice is associated with alterations of the glucocorticoid/adrenocorticotropic hormone axis, and translated in high bone mass and enhanced bone formation. Since the cellular alterations underlying the enhanced bone formation remain unknown, we investigated Scarb1-deficient marrow stromal cells (MSC) behavior in vitro. No difference in HDL₃, cholesteryl ester (CE) or estradiol (E) association/binding was measured between Scarb1-null and wild-type (WT) cells. Scarb1 genic expression was down-regulated twofold following osteogenic treatment. Neither WT nor null cell proliferation was influenced by HDL₃ exposure whereas this condition decreased genic expression of osteoblastic marker osterix (Sp7), and osteocyte markers sclerostin (Sost) and dentin matrix protein 1 (Dmp1) independently of genotype. Sost and Dmp1 basal expression in null cells was 40% and 50% that of WT cells; accordingly, osteocyte density was 20% lower in vertebrae from Scarb1-null mice. Genic expression of co-receptors for Wnt signaling, namely LDL-related protein (Lrp) 5 and Lrp8, was increased, respectively, by two- and threefold, and of transcription target-genes axis inhibition protein 2 (Axin2) and lymphoid enhancer-binding factor 1 (Lef1) over threefold. Gene expression of Wnt signaling agonist Wnt5a and of the antagonist dickkopfs-related protein 1 (Dkk1) were found to be increased 10- to 20-fold in null MSC. These data suggest alterations of Wnt pathways in Scarb1-deficient MSC potentially explaining their enhanced function, hence contributing to the high bone mass observed in these mice.

【 授权许可】

CC BY   
© 2014 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.