title: Lentivirus-TAZ Administration Alleviates Osteoporotic Phenotypes in the Femoral Neck of Ovariectomized Rats.
abstract: BACKGROUND
  Osteoporosis is characterized by impairment of bone mass, strength, and microarchitecture, leading to the susceptibility to fragility fractures, especially in femoral neck region. Transcriptional coactivator with PDZ-binding motif (TAZ) facilitates osteogenesis while suppressing adipogenesis via regulation of transcriptional activities of runt-related transcription factor 2 and peroxisome proliferator-activated receptor x03B3;. Here, we validated the role of TAZ in vivo using an ovariectomized (OVX) rat model of osteoporosis.
  
  
  METHODS
  Serum alkaline phosphatase, triglyceride, cholesterol and urinary hydroxyproline were measured on an automatic analyzer using diagnostic reagent kits. Serum OCN and C-terminal cross-linked telopeptides of type I collagen were measured using ELISA. Bone mineral density was measured using dual-energy X-ray scanner. Mechanical parameters were detected by three-point bending assays. Bone volume per tissue volume (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. No), and trabecular separation (Tb. Sp) were measured by MicroCT. The mRNA and protein levels were quantified by Realtime PCR and Western Blotting respectively.
  
  
  RESULTS
  After injections of lentivirus overexpressing TAZ into the femoral neck region, bone mineral density, ultimate force, stiffness, BV/TV, Tb. Th, and Tb. No were significantly increased, whereas Tb. Sp was dramatically decreased. In the TAZ-overexpression region in the femoral neck of OVX rats, the mRNA levels of Runx2 and osteocalcin were obviously elevated, whereas that of PPARx03B3; and adipocyte protein 2 were downregulated.
  
  
  CONCLUSIONS
  Lentivirus-mediated TAZ gene therapy alleviated the osteoporotic phenotypes in the femoral neck of OVX rats, providing an alternative strategy for the treatment of postmenopausal osteoporosis and prevention of osteoporotic fracture.
authors.affiliation: Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xix2018;an, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Zheyang
authors.initials: Z
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Ding
authors.forename: Ainiwaerjiang
authors.initials: A
authors.lastname: Damaolar
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Li
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Qiu
authors.forename: Zhanhai
authors.initials: Z
authors.lastname: Yin
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density; D024042:Collagen Type I / Q000097:blood / Q000737:chemistry; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005272:Femur Neck / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D017930:Genes, Reporter; D016086:Lentivirus / Q000235:genetics*; D015675:Osteocalcin / Q000097:blood / Q000235:genetics / Q000378:metabolism; D010024:Osteoporosis / Q000378:metabolism / Q000473:pathology; D010052:Ovariectomy; D054731:PDZ Domains / Q000235:genetics*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D051381:Rats; D017207:Rats, Sprague-Dawley; D055114:X-Ray Microtomography
chemical_list: D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; C524662:FABP4 protein, rat; D050556:Fatty Acid-Binding Proteins; D047495:PPAR gamma; D015675:Osteocalcin