title: Effects of p-glycoprotein on steroid-induced osteonecrosis of the femoral head.
abstract: P-glycoprotein (P-gp) activity may play an important role in steroid-induced osteonecrosis of the femoral head (ONF); however, the precise mechanism of its pathogenesis remains unknown. Therefore, we investigated the effects of increased P-gp activity on steroid-induced ONF using a rat model. Rats (n = 60) were treated with either a pharmacological stimulant of P-gp, rifampicin (group A); a suppressant, verapamil (group B); or normal saline (group C) administered in conjunction with methylprednisolone, an inducer of ONF. P-gp activity in bone marrow cells and expression in the femoral head significantly increased in group A (P < 0.05) but decreased in group B (P < 0.05). Likewise, the serum osteocalcin level, trabecular thickness and number, osteoclast and osteoblast numbers, and mean percentage of the epiphyseal ossification center were significantly increased in group A (P < 0.01) but decreased in group B (P < 0.01). In contrast, however, adipocytic variables, trabecular separation, and apoptotic cells decreased in group A (P < 0.01) but increased in group B (P < 0.01). The ONF incidence in group A (50%) and group B (100%) was significantly different from that in the control group C (80%, P < 0.05). Taken together, our findings suggested that enhanced P-gp activity was able to decrease the risk of steroid-induced ONF, possibly by inhibiting adipogenesis and apoptosis in the femoral head.
authors.affiliation: Zhongshan Hospital of Fudan University, 180 Fenglin Road, Shanghai, 200032, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Han
authors.forename: Zuoqin
authors.initials: Z
authors.lastname: Yan
authors.forename: Chang-an
authors.initials: CA
authors.lastname: Guo
authors.forename: Feng
authors.initials: F
authors.lastname: Shen
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Yuxing
authors.initials: Y
authors.lastname: Shi
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D050156:Adipogenesis / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002452:Cell Count; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005271:Femur Head Necrosis / Q000139:chemically induced* / Q000378:metabolism*; D005938:Glucocorticoids / Q000009:adverse effects*; D008297:Male; D010006:Osteoblasts / Q000473:pathology; D010010:Osteoclasts / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012293:Rifampin / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D014700:Verapamil; D012293:Rifampin