Plasticizer Di(2-ethylhexyl)phthalate Interferes with Osteoblastogenesis and Adipogenesis in a Mouse Model.

Plasticizer Di(2-ethylhexyl)phthalate Interferes with Osteoblastogenesis and Adipogenesis in a Mouse Model.

J Orthop Res. 2017 Sep 16;:

Authors: Chiu CY, Sun SC, Chiang CK, Wang CC, Chan DC, Chen HJ, Liu SH, Yang RS

Abstract Plasticizer di(2-ethylhexyl)phthalate (DEHP) can leach from medical devices such as blood storage bags and the tubing. Recently, epidemiological studies showed that phthalate metabolites levels in the urine are associated with low bone mineral density (BMD) in older women. The detailed effect and mechanism of DEHP on osteoblastogenesis and adipogenesis and bone loss remain to be clarified. Here, we investigated the effect and mechanism of DEHP and its active metabolite mono(2 -ethylhexyl)phthalate (MEHP) on osteoblastogenesis and adipogenesis. The in vitro study showed that osteoblast differentiation of bone marrow stromal cells (BMSCs) was significantly and dose -dependently decreased by DEHP and MEHP (10 -100 μM) without cytotoxicity to BMSCs. The mRNA expressions of alkaline phosphatase, Runx2, osteocalcin, Wnt1, and β -catenin were significantly decreased in DEHP - and MEHP -treated BMSCs during differentiation. MEHP, but not DEHP, significantly increased the adipocyte differentiation of BMSCs and PPARγ mRNA expression. Both DEHP and MEHP significantly increased the ratios of phosphorylated β -catenin/β -catenin and inhibited osteoblastogenesis, which could be reversed by Wnt activator lithium chloride and PPARγ inhibitor T0070907. Moreover, exposure of mice to DEHP (1, 10, and 100 mg/kg) for 8 weeks altered BMD and microstructure. In BMSCs isolated from DEHP -treated mice, osteoblastogenesis and Runx2, Wnt1, and β -catenin expression were decreased, but adipogenesis and PPARγ expression were increased. These findings suggest that DEHP and its metabolite MEHP exposure may inhibit osteoblastogenesis and promote adipogenesis of BMSCs through the Wnt/β -catenin -regulated and thus triggering bone loss. PPARγ signaling may play an important role in MEHP - and DEHP -induced suppression of osteogenesis. This article is protected by copyright. All rights reserved.

PMID: 28921615 [PubMed - as supplied by publisher]