title: Protective effects of necrostatin-1 on glucocorticoid-induced osteoporosis in rats.
abstract: The inhibition of bone formation has been suggested to play a central role in the pathogenesis of glucocorticoid-induced osteoporosis (GIOP). Recently, many studies suggested that there may be another mechanism involved in GIOP besides apoptosis. The aim of this study was to investigate the protective effect of Necrostatin-1 on GIOP rats. Forty male Sprague-Dawley rats were randomly divided into four groups (n=10): controls; GIOP rats; GIOP rats pretreated with alendronate; and GIOP rats pretreated with Necrostatin-1. Their bone mineral density (BMD) and body weight were measured at the beginning and at the end of the experiment. TUNEL assay, transmission electron microscopy (TEM) and scanning electron microscopy (SEM) were used to observe the change of cellular morphology induced by Nec-1. The biochemical analysis and histomorphometric analysis were used to evaluate the change of bone formation by Nec-1. RIP-1, RIP-3 and caspase-8 expression were evaluated by immunohistochemistry. We found more TUNEL positive osteocytes and larger lacunae volume in GIOP rats compared with the control group. However, most of the osteocytes displayed a necrotic morphology and mitochondria lesions under TEM. In contrast to alendronate, Necrostatin-1 significantly elevated the level of bone formation markers, while it had no effect on bone resorption markers. Necrostatin-1 also markedly ameliorated trabecular bone. In addition, Necrostatin-1 significantly weaken the immunoreactivity of RIP-1 in GIOP rats while had no effect on RIP-3 and caspase-8. These data suggest, for the first time, that Necrostatin-1 accelerate bone formation of glucocorticoid-induced osteoporosis in rats.
authors.affiliation: Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University No.157 Xiwu Road, Xi'an, Shaanxi Province, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.affiliation: Department of ICU, 521 Healthy Institutes of North Industries, No. 12 Zhangbadong Road, Xi'an, Shaanxi Province, PR China.
authors.forename: RuiRui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Chinese Medicine Hospital of Xi'an, No. 325 Dongda Street, Xi'an, Shaanxi Province, PR China.
authors.forename: Futai
authors.initials: F
authors.lastname: Gong
authors.affiliation: Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University No.157 Xiwu Road, Xi'an, Shaanxi Province, PR China.
authors.forename: Pei
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University No.157 Xiwu Road, Xi'an, Shaanxi Province, PR China.
authors.forename: Lihong
authors.initials: L
authors.lastname: Fan
authors.affiliation: Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University No.157 Xiwu Road, Xi'an, Shaanxi Province, PR China.
authors.forename: Jianlong
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University No.157 Xiwu Road, Xi'an, Shaanxi Province, PR China.
authors.forename: Wenchao
authors.initials: W
authors.lastname: Bi
authors.affiliation: Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University No.157 Xiwu Road, Xi'an, Shaanxi Province, PR China.
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University No.157 Xiwu Road, Xi'an, Shaanxi Province, PR China.
authors.forename: ChunSheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Second Affiliated Hospital of Xi'an Jiaotong University No.157 Xiwu Road, Xi'an, Shaanxi Province, PR China. Electronic address: syo0817@163.com.
authors.forename: KunZheng
authors.initials: K
authors.lastname: Wang
mesh_terms: D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D053181:Caspase 8 / Q000378:metabolism; D003907:Dexamethasone; D005269:Femur / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005938:Glucocorticoids; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D010011:Osteocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010024:Osteoporosis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D050071:Bone Density Conservation Agents; D005938:Glucocorticoids; D007093:Imidazoles; D007211:Indoles; C507699:necrostatin-1; D003907:Dexamethasone; D017346:Protein Serine-Threonine Kinases; C586536:RIPK1 protein, rat; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C582791:Ripk3 protein, rat; C505528:Casp8 protein, rat; D053181:Caspase 8
keywords: Caspase-8; Glucocorticoid; Necroptosis; Necrostatin-1; Osteoporosis