P‐glycoprotein overexpression in bone marrow–derived multipotent stromal cells decreases the risk of steroid‐induced osteonecrosis in the femoral head

Autor: Zhengdong Cai, Yingqi Hua, Chong Xu, Zuoqin Yan, Ning Han, Zengchun Li
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
ATP Binding Cassette Transporter
Subfamily B
Stromal cell
bone marrow–derived multipotent stromal cell
Green Fluorescent Proteins
Peroxisome proliferator-activated receptor
osteogenesis
Green fluorescent protein
Rats
Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
stomatognathic system
Femur Head Necrosis
In vivo
Internal medicine
P‐glycoprotein
medicine
Animals
ATP Binding Cassette Transporter
Subfamily B
Member 1
Femur
Transgenes
chemistry.chemical_classification
Adipogenesis
Chemistry
osteonecrosis
Cell Differentiation
Mesenchymal Stem Cells
Original Articles
Cell Biology
RUNX2
030104 developmental biology
Endocrinology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Immunology
Molecular Medicine
Alkaline phosphatase
Steroids
Original Article
Bone marrow
Stem Cell Transplantation
Zdroj: Journal of Cellular and Molecular Medicine
ISSN: 1582-4934
1582-1838
Popis: P‐glycoprotein (P‐gp) plays a role in steroid‐induced osteonecrosis of the femoral head (ONFH), but the underlying mechanism remains unknown. We hypothesized that P‐gp overexpression can prevent ONFH by regulating bone marrow–derived multipotent stromal cell (BMSC) adipogenesis and osteogenesis. BMSCs from Sprague–Dawley rats were transfected with green fluorescent protein (GFP) or the multidrug resistance gene 1 (MDR1) encoding GFP and P‐gp. Dexamethasone was used to induce BMSC differentiation. Adipogenesis was determined by measuring peroxisome proliferator‐activated receptor (PPAR‐γ) expression and the triglyceride level. Osteogenesis was determined by measuring runt‐related transcription factor 2 (Runx2) expression and alkaline phosphatase activity. For in vivo experiments, rats were injected with saline, BMSCs expressing GFP (GFP‐BMSCs) or BMSCs expressing GFP‐P‐gp (MDR1‐GFP‐BMSCs). After dexamethasone induction, adipogenesis was determined by measuring PPAR‐γ expression and fatty marrow, whereas osteogenesis was detected by measuring Runx2 expression, trabecular parameters and the mineral apposition rate, followed by evaluation of the incidence of ONFH. Overexpression of P‐gp in BMSCs resulted in markedly decreased expression of adipogenic markers and increased expression of osteogenic markers. Compared with rats injected with saline, rats injected with GFP‐BMSCs showed reduced ONFH, and the injected GFP‐positive BMSCs attached to trabecular surfaces and exhibited an osteoblast‐like morphology. Compared with the rats injected with BMSCs expressing GFP alone, rats injected with BMSCs overexpressing GFP and P‐gp showed lower adipocytic variables, higher osteogenic variables and lower incidence of ONFH. Overexpression of P‐gp inhibited BMSC adipogenesis and promoted osteogenesis, which reduced the incidence of steroid‐induced ONFH.
Databáze: OpenAIRE
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