Open AccessGlucocorticoids decreased Cx43 expression in osteonecrosis of femoral head: The effect on proliferation and osteogenic differentiation of rat BMSCs
Author(s) -
Zhao Xin,
Alqwbani Mohammed,
Luo Yue,
Chen Changjun,
A Ge,
Wei Yang,
Li Donghai,
Wang Qiuru,
Tian Meng,
Kang Pengde
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16103
Subject(s) - runx2 , glucocorticoid , dexamethasone , chemistry , transfection , methylprednisolone , in vitro , lipopolysaccharide , immunofluorescence , microbiology and biotechnology , andrology , immunology , endocrinology , medicine , osteoblast , biology , gene , antibody , biochemistry
Glucocorticoid (GC)‐induced osteonecrosis of the femoral head (GC‐ONFH) is considered as one of the most serious side effects of long‐term or over‐dose steroid therapy. However, the underlying cause mechanisms are still not fully investigated. We firstly established a rat model of GC‐ONFH and injected lipopolysaccharide (LPS) and methylprednisolone (MPS). We found that the expressions of Cx43, Runx2, ALP and COLⅠ were more decreased than the normal group. Secondly, the isolated rat bone marrow stem cells (BMSCs) were treated with dexamethasone (Dex) in vitro, and the expressions of Cx43, Runx2, ALP and COLⅠ were decreased significantly. Moreover, the results of immunofluorescence staining, alizarin red staining, EdU assay and CCK8 showed that the osteogenic differentiation and the proliferation capacity of BMSCs were decreased after induced by Dex. A plasmid of lentivirus‐mediated Cx43 (Lv‐Cx43) gene overexpression was established to investigate the function of Cx43 in BMSCs under the Dex treatment. Findings demonstrated that the proliferation and osteogenic differentiation abilities were enhanced after Lv‐Cx43 transfected to BMSCs, and these beneficial effects of Lv‐Cx43 were significantly blocked when PD988059 (an inhibitor of ERK1/2) was used. In conclusion, the overexpression of Cx43 could promote the proliferation and osteogenic differentiation of BMSCs via activating the ERK1/2 signalling pathway, which provide a basic evidence for further study on the detailed function of Cx43 in GC‐ONFH.