Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 25, Issue 1, Pages 484-498Publisher
WILEY
DOI: 10.1111/jcmm.16103
Keywords
bone marrow mesenchymal stem cells; connexin43; dexamethasone; ERK1; 2 signalling pathway; osteonecrosis of femoral head
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Funding
- National Natural Science Foundation of China [81672165, 81974333, 81401528]
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In a study on GC-ONFH induced by steroid therapy, decreased expression of Cx43 protein was found to impact the proliferation and osteogenic differentiation abilities of bone marrow stem cells. Overexpression of Cx43 protein was shown to promote the proliferation and osteogenic differentiation of BMSCs through activation of the ERK1/2 signaling pathway.
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 COLROMAN NUMERAL ONE 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 COLROMAN NUMERAL ONE 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.
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