title: MiR-708 promotes steroid-induced osteonecrosis of femoral head, suppresses osteogenic differentiation by targeting SMAD3.
abstract: Steroid-induced osteonecrosis of femoral head (ONFH) is a serious complication of glucocorticoid (GC) use. We investigated the differential expression of miRs in the mesenchymal stem cells (MSCs) of patients with ONFH, and aimed to explain the relationship between GC use and the development of MSC dysfunction in ONFH. Cells were collected from bone marrow of patients with ONFH. Samples were assigned to either GCs Group or Control Group at 1:1 matched with control. We then used miRNA microarray analysis and real-time PCR to identify the differentially expressed miRs. We also induced normal MSCs with GCs to verify the differential expression above. Subsequently, we selected some of the miRs for further studies, including miRNA target and pathway prediction, and functional analysis. We discovered that miR-708 was upregulated in ONFH patients and GC-treated MSCs. SMAD3 was identified as a direct target gene of miR-708, and functional analysis demonstrated that miR-708 could markedly suppress osteogenic differentiation and adipogenesis differentiation of MSCs. Inhibition of miR-708 rescued the suppressive effect of GC on osteonecrosis. Therefore, we determined that GC use resulted in overexpression of miR-708 in MSCs, and thus, targeting miR-708 may serve as a novel therapeutic biomarker for the prevention and treatment of ONFH.
authors.affiliation: Orthopedic Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Hao
authors.affiliation: Orthopedic Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Shuhua
authors.initials: S
authors.lastname: Yang
authors.affiliation: Orthopedic Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Xu
authors.affiliation: Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, Massachusetts 02114.
authors.forename: Jacson K
authors.initials: JK
authors.lastname: Shen
authors.affiliation: Orthopedic Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Shunan
authors.initials: S
authors.lastname: Ye
authors.affiliation: Orthopedic Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Xianzhe
authors.initials: X
authors.lastname: Liu
authors.affiliation: Orthopedic Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Orthopedic Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.
authors.forename: Baojun
authors.initials: B
authors.lastname: Xiao
authors.affiliation: Orthopedic Hospital, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China.|Sarcoma Biology Laboratory, Department of Orthopaedic Surgery, Massachusetts General Hospital and Harvard Medical School, 55 Fruit Street, Jackson 1115, Boston, Massachusetts 02114.
authors.forename: Yong
authors.initials: Y
authors.lastname: Feng
mesh_terms: D020413:3' Untranslated Regions; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D005271:Femur Head Necrosis / Q000139:chemically induced* / Q000235:genetics; D005938:Glucocorticoids / Q000009:adverse effects*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010012:Osteogenesis / Q000235:genetics*; D051900:Smad3 Protein / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D005938:Glucocorticoids; C568528:MIRN708 microRNA, human; D035683:MicroRNAs; C497790:SMAD3 protein, human; D051900:Smad3 Protein