title: STAT1-caspase 3 pathway in the apoptotic process associated with steroid-induced necrosis of the femoral head.
abstract: Osteocyte apoptosis is the main manifestation of steroid-induced avascular necrosis of the femoral head (SANFH). STAT1 and caspase 3 participate in the process of apoptosis and STAT1 upregulates the expression of caspase 3. We examined the relationship between the STAT1-caspase 3 pathway and apoptosis in SANFH. All specimens were divided into four groups: the negative control group, Ficat I-II group, Ficat III group, and Ficat IV-V group, and examined histologically, with a TUNEL assay, immunohistochemically, with a caspase 3 activity assay, with ELISAs of STAT1 and phospo-STAT1 (p-STAT1), with a western blotting analysis of p-STAT1 and with real-time RT-PCR. The proportion of empty lacunae increased significantly with the development of SANFH. The proportion of TUNEL-positive cells and immunohistochemical analysis of caspase 3 also increased significantly, although the Ficat I-II group did not differ significantly from the negative control group. Immunohistochemical analysis of STAT1 and p-STAT1, caspase 3 activity all showed significant differences among the groups. An ELISA and a western blotting analysis of p-STAT1 showed significant differences among the groups. An ELISA of STAT1, real-time RT-PCR analysis of caspase 3 and STAT1 all showed significant differences among the groups except between the Ficat I-II and negative control groups. The correlation analysis showed strong positive relationships between the proportion of empty lacunae and the proportion of TUNEL-positive cells between caspase 3 activity and the proportion of TUNEL-positive cells and between the levels of p-STAT1 protein and caspase 3 mRNA. The apoptotic process in SANFH develops with the upregulated expression of caspase 3 via the expression and activation of STAT1. The STATI-caspase 3 pathway plays a critical role in the development of SANFH.
authors.affiliation: Osteopathy Department, Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xinxian
authors.initials: X
authors.lastname: Xu
authors.forename: Hong
authors.initials: H
authors.lastname: Wen
authors.forename: Yuezheng
authors.initials: Y
authors.lastname: Hu
authors.forename: Huachen
authors.initials: H
authors.lastname: Yu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chengwang
authors.initials: C
authors.lastname: Chen
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Pan
mesh_terms: D000328:Adult; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005271:Femur Head Necrosis / Q000139:chemically induced* / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D013256:Steroids / Q000633:toxicity
chemical_list: D050794:STAT1 Transcription Factor; D013256:Steroids; D053148:Caspase 3