Nabi Fazul, Iqbal Muhammad K, Zhang Hui, Rehman Mujeeb Ur, Shahzad Muhammad, Huang Shucheng, Han Zhaoqing, Mehmood Khalid, Ahmed Nisar, Chachar Bahram, Arain Muhammad A, Li Jiakui
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
Faculty of Veterinary and Animal Science, Lasbela University of Agriculture, Water and Marine Sciences, Uthal, Balochistan, Pakistan.
J Vet Pharmacol Ther. 2018 Dec;41(6):902-911. doi: 10.1111/jvp.12692. Epub 2018 Jul 13.
Tibial dyschondroplasia (TD) is a bone defect of broilers and other poultry birds that disturbs growth plate and it causes lameness. Previously we evaluated differential expression of multiple genes involved in growth plate angiogenesis and reported the safety and efficacious of medicinal plant root extracted for controlling TD. In this study, clinical and protective effect of an antibiotic Novobiocin (Hsp90 inhibitor) and expression of Hsp90 and proteoglycan aggrecan was examined. The chicks were divided into three groups; Control, thiram-induced TD, and Novobiocin injected TD. After the induction of TD, the Novobiocin was administered through intraperitoneal route to TD-affected birds until the end of the experiment. The expressions and localization of Hsp90 were evaluated by qRT-PCR, immunohistochemistry (IHC) and western blot, respectively. Morphological, histological examinations, and serum biomarker levels were evaluated to assess specificity and protective effects of Novobiocin. The results showed that TD causing retarded growth, enlarged growth plate, distended chondrocytes, irregular columns of cells, decreased antioxidant capacity, reduced protein levels of proteoglycan aggrecan, and upregulated in Hsp90 expression (p < 0.05) in dyschondroplastic birds as compared with control. Novobiocin treatment restored growth plate morphology, reducing width, stimulated chondrocyte differentiation, sprouting blood vessels, corrected oxidative imbalance, decreased Hsp90 expressions and increased aggrecan level. Novobiocin treatment controlled lameness and improved growth in broiler chicken induced by thiram. In conclusion, the accumulation of the cartilage and up-regulated Hsp90 are associated with TD pathogenesis and irregular chondrocyte morphology in TD is along with reduced aggrecan levels in the growth plate. Our results indicate that Novobiocin treatment has potential to reduce TD by controlling the expression of Hsp90 in addition to improve growth and hepatic toxicity in broiler chicken.
胫骨软骨发育不良（TD）是肉鸡和其他家禽的一种骨缺陷，会扰乱生长板并导致跛行。此前我们评估了参与生长板血管生成的多个基因的差异表达，并报道了从药用植物根中提取的物质对控制TD的安全性和有效性。在本研究中，检测了抗生素新生霉素（Hsp90抑制剂）的临床和保护作用以及Hsp90和蛋白聚糖聚集蛋白聚糖的表达。将雏鸡分为三组：对照组、福美双诱导的TD组和注射新生霉素的TD组。诱导TD后，通过腹腔途径给受TD影响的鸡施用新生霉素直至实验结束。分别通过qRT-PCR、免疫组织化学（IHC）和蛋白质印迹法评估Hsp90的表达和定位。评估形态学、组织学检查和血清生物标志物水平以评估新生霉素的特异性和保护作用。结果表明，与对照组相比，TD导致发育迟缓、生长板增大、软骨细胞肿胀、细胞柱不规则、抗氧化能力降低、蛋白聚糖聚集蛋白聚糖的蛋白质水平降低以及发育不良鸡中Hsp90表达上调（p<0.05）。新生霉素治疗恢复了生长板形态，减小了宽度，刺激了软骨细胞分化、血管生成，纠正了氧化失衡，降低了Hsp90表达并增加了聚集蛋白聚糖水平。新生霉素治疗控制了由福美双诱导的肉鸡跛行并改善了生长。总之，软骨的积累和Hsp90上调与TD发病机制有关，TD中不规则的软骨细胞形态与生长板中聚集蛋白聚糖水平降低有关。我们的结果表明，新生霉素治疗除了改善肉鸡生长和肝毒性外，还有潜力通过控制Hsp90的表达来降低TD。
