Efficiency of Cell Therapy to GC-Induced ONFH: BMSCs with Dkk-1 Interference Is Not Superior to Unmodified BMSCs.

Abstract:

:Glucocorticoid-induced osteonecrosis of the femoral head (ONFH) is a hip disorder, and it threatens patients who require megadose of steroid therapies. Nowadays, no valid therapies can reverse the development of GC-induced ONFH once it occurs. Stem cell therapy to GC-induced ONFH would be a promising choice. Although the pathogenesis of GC-induced ONFH is not yet fully clear, Dickkopf-1 (Dkk-1) upregulated by excessive GC use, which hinders the canonical Wnt pathway, could be an explanation. Thus, the aim of the present work lies in investigating the efficiency of the allograft bone marrow stem cells (BMSCs) with Dkk-1 interference in preventing the progression of the GC-induced ONFH. Lentivirus-meditated Dkk-1 RNAi was introduced into BMSCs which was exposed to dexamethasone (10-6 mol/L) in vitro. This interference blocked Dkk-1 overexpression by GC and afterwards prompted the transduction of Wnt/β-catenin in which the Runx2 and PPARγ were upregulated and downregulated, respectively. Thus, the osteogenesis was promoted while adipogenesis was inhibited. In vivo, GC-induced ONFH rats were treated by allotransplantation of BMSCs with Dkk-1 interference, and the progression of the disease was prevented. However, the effects were not significantly superior to treatment with nongenetically modified or normal BMSCs.

journal_name

Stem Cells Int

journal_title

Stem cells international

authors

Zhun W,Donghai L,Zhouyuan Y,Haiyan Z,Pengde K

doi

10.1155/2018/1340252

subject

Has Abstract

pub_date

2018-05-22 00:00:00

pages

1340252

eissn

1687-966X

issn

1687-9678

journal_volume

2018

pub_type

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