title: Hsp90 inhibitor celastrol reinstates growth plate angiogenesis in thiram-induced tibial dyschondroplasia.
abstract: Tibial dyschondroplasia (TD) is an important long bone defect of broiler chickens that disturbs the proximal growth plate and is characterized by non-vascularized cartilage, a distended growth plate and lameness. Celastrol, a medicinal root extract from the plant Tripterygium wilfordii, is reported widely as a well-known heat-shock protein 90 (Hsp90) inhibitor. Recently, Hsp90 inhibition in chondrocyte differentiation and growth-plate vascularization were effective in restoring the morphology of the growth plate. The present study was aimed at investigating Hsp90 inhibition in TD using celastrol. The broiler chicks were divided into three groups; Control; TD induced (40 mg/kg thiram) and celastrol treatment. Hsp90, vascular endothelial growth factor and Flk-1 expressions were evaluated by quantitative real-time polymerase chain reaction and the protein levels of Hsp90 were measured by Western blot analysis. Antioxidant enzymes were determined to assess the liver damage caused by thiram and the protective effects of the medicine were evaluated by levels of serum biomarkers. The expression levels of Hsp90 and vascular endothelial growth factor mRNA transcripts were increased while Flk-1 receptor was decreased in TD-affected chicks. Celastrol therapy inhibited Hsp90 mRNA and protein levels and up-regulated the expressions of receptor Flk-1 in TD-affected tibial growth plates significantly (P < 0.05) in addition to rectifying the damaging effects of thiram on the liver by decreasing the levels of aspartate aminotransferase, alanine aminotransferase and malondialdehyde and correcting the oxidative imbalance. In conclusion, administering celastrol to dyschondroplastic chicks prevented un-vascularized growth plate, lameness and reinstated angiogenesis. Celastrol may be efficacious for the treatment of TD through the inhibition of Hsp90 expression and limiting the liver damage caused by thiram in broiler chickens.
authors.affiliation: a Department of Clinical Veterinary Medicine , College of Veterinary Medicine, Huazhong Agricultural University , Wuhan , People's Republic of China.|b Faculty of Veterinary and Animal Sciences , Lasbela University of Agriculture, Water and Marine Sciences , Uthal , Balochistan , Pakistan.
authors.forename: Fazul
authors.initials: F
authors.lastname: Nabi
authors.affiliation: a Department of Clinical Veterinary Medicine , College of Veterinary Medicine, Huazhong Agricultural University , Wuhan , People's Republic of China.|c University College of Veterinary and Animal Sciences, The Islamia University of Bahawalpur , Bahawalpur , Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Shahzad
authors.affiliation: a Department of Clinical Veterinary Medicine , College of Veterinary Medicine, Huazhong Agricultural University , Wuhan , People's Republic of China.
authors.forename: Jingying
authors.initials: J
authors.lastname: Liu
authors.affiliation: a Department of Clinical Veterinary Medicine , College of Veterinary Medicine, Huazhong Agricultural University , Wuhan , People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Li
authors.affiliation: a Department of Clinical Veterinary Medicine , College of Veterinary Medicine, Huazhong Agricultural University , Wuhan , People's Republic of China.
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Han
authors.affiliation: a Department of Clinical Veterinary Medicine , College of Veterinary Medicine, Huazhong Agricultural University , Wuhan , People's Republic of China.
authors.forename: Ding
authors.initials: D
authors.lastname: Zhang
authors.affiliation: a Department of Clinical Veterinary Medicine , College of Veterinary Medicine, Huazhong Agricultural University , Wuhan , People's Republic of China.
authors.forename: Muhammad Kashif
authors.initials: MK
authors.lastname: Iqbal
authors.affiliation: a Department of Clinical Veterinary Medicine , College of Veterinary Medicine, Huazhong Agricultural University , Wuhan , People's Republic of China.
authors.forename: Jiakui
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D002645:Chickens / Q000254:growth & development*; D006132:Growth Plate / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D008297:Male; D010009:Osteochondrodysplasias / Q000139:chemically induced / Q000517:prevention & control / Q000662:veterinary*; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D011201:Poultry Diseases / Q000139:chemically induced / Q000517:prevention & control*; D012333:RNA, Messenger / Q000235:genetics; D013893:Thiram / Q000009:adverse effects; D013977:Tibia / Q000187:drug effects; D029757:Tripterygium / Q000737:chemistry*; D014315:Triterpenes / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000187:drug effects / Q000235:genetics
chemical_list: D018841:HSP90 Heat-Shock Proteins; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D012333:RNA, Messenger; D014315:Triterpenes; D042461:Vascular Endothelial Growth Factor A; D013893:Thiram; C050414:celastrol
keywords: Angiogenesis; Hsp90; bone; celastrol; chicken; liver; tibial dyschondroplasia; traditional Chinese medicine