Open AccessSclerostin is upregulated in the early stage of chondrogenic differentiation, but not required in endochondral ossification in vitro
Author(s) -
Yuuki Yamaguchi,
Ken Kumagai,
Sosuke Imai,
Kazuma Miyatake,
T. Saito
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0201839
Subject(s) - sclerostin , endochondral ossification , chondrogenesis , wnt signaling pathway , runx2 , sox9 , microbiology and biotechnology , chemistry , medicine , downregulation and upregulation , endocrinology , ossification , cartilage , signal transduction , osteoblast , biology , anatomy , biochemistry , stem cell , gene expression , in vitro , gene
Sclerostin is a potent inhibitor of the canonical Wnt signaling pathway. Wnt signaling pathways have multiple roles in the regulation of cartilage development, growth, and maintenance. This study focused on the role of sclerostin in the process of chondrogenic differentiation. We hypothesized that sclerostin is essential to induce chondrogenic differentiation and regulate endochondral ossification. ATDC5 cells were used to investigate chondrogenic differentiation and terminal calcification. During chondrogenic differentiation, intrinsic sclerostin was upregulated in the early stage, but downregulated in the late stage. Addition of sclerostin elevated expressions of Sox9 and Col2a1 (P<0.05) and reduced expressions of Runx2, Col10a1, MMP-3, MMP-13, and ADAMTS5 (P<0.05) through inhibition of the Wnt-β-catenin signaling pathway (P<0.05). Terminal calcification was significantly inhibited by sclerostin (P<0.05). In contrast, deletion of sclerostin decreased expressions of Sox9 and Col2a1 (P<0.05), increased expressions of Runx2, Col10a1, MMP-3, and MMP-13 (P<0.05), and promoted terminal calcification (P<0.05). This study provides insights into the possible role of sclerostin in the regulation of chondrogenic differentiation. Sclerostin is upregulated in the early stage of chondrogenic differentiation, but is not required in endochondral ossification. Sclerostin is a candidate modulator for chondrogenic differentiation.