Chinese Journal of Tissue Engineering Research ›› 2016, Vol. 20 ›› Issue (4): 492-496.doi: 10.3969/j.issn.2095-4344.2016.04.007

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Inflammatory reactions-STAT signaling pathway in the mechanism underlying titanium metal ion-mediated osteolysis 

Zhao Wen-jie1, Dai Min1, Zhang Bin2, Wan Xi-zhen1, Fan Hong-xian1   

  1. 1Department of Orthopedics, the First Affiliated Hospital, Nanchang University, Nanchang 330006, Jiangxi Province, China; 2Jiangxi Province Artificial Joint Engineering Technology Research Center, Nanchang 330006, Jiangxi Province, China
  • Received:2015-11-19 Online:2016-01-22 Published:2016-01-22
  • Contact: Fan Hong-xian, Department of Orthopedics, the First Affiliated Hospital, Nanchang University, Nanchang 330006, Jiangxi Province, China
  • About author:Zhao Wen-jie, Master, Department of Orthopedics, the First Affiliated Hospital, Nanchang University, Nanchang 330006, Jiangxi Province, China
  • Supported by:

    the Science and Technology Research Project of Jiangxi Provincial Department of Education, No. GJJ12067; the Jiangxi Provincial Science and Technology Department Guidance Plan, No. 2010ZDS00700

Abstract:

BACKGROUND: Inhibition of osteolysis is an important manner to reduce prosthesis loosening, but the mechanism of osteolysis is still unclear.
OBJECTIVE: To analyze the correlation of inflammatory reaction-JAK/STAT signal transduction pathway and titanium metal ion-mediated osteolysis. 
METHODS: A total of 50 Kunming mice were divided into five groups. In the sham group, the cranium was injected with physiological saline. In other four groups, the cranium was injected with titanium metal wear particle suspension to establish models of calvarial osteolysis. On day 2 after model establishment, mice in three groups were separately intraperitoneally injected with low-, moderate- and high-dose (1, 10, 100 μmol/L) JAK inhibitor  
AG490 10 mL/kg, once a day. 28 days later, osteolysis area, number of osteoclasts, tumor necrosis factor α, vascular endothelial growth factor and interleukin-10 levels, JAK1/2/3 and STAT1/3 protein expression, and Caspase3/9 protein expression were detected in each group.
RESULTS AND CONCLUSION: (1) Compared with the sham surgery group, osteolysis area of mice was significantly larger in the model group (P < 0.01), and the number of osteoclast was significantly more, and inflammatory factor levels were significantly higher (P < 0.01). JAK/STAT signaling pathway protein and apoptotic protein expressions were significantly higher (all P < 0.01). (2) Compared with the model group, osteolysis area was smaller, the number of osteoclasts was less, inflammatory factor levels were significantly less, JAK/STAT signaling pathway protein and apoptotic protein expression was significantly less in the moderate- and high-dose AG490 groups (all P < 0.01). (3) These findings suggested that JAK inhibitor AG490 alleviates titanium metal ion-mediated osteolysis by inhibiting inflammatory reactions and JAK/STAT signaling transduction pathway.