title: [Expression of mRNA and protein of p38, Osx, PI3K and Akt1 in rat bone with chronic fluorosis].
abstract: OBJECTIVE
  To investigate the expressions of mRNA and protein of p38, Osx, PI3K, Akt1 in the rats bone with chronic fluorosis.
  
  
  METHODS
  Dental fluorosis were observed and the fluoride contents in the urine and bone were detected by fluorin-ion selective electrode. The morphologic changes and ultrastructure of rats' bone were observed by light and electronic microscopy. The expressions of protein and mRNA of p38, Osx, PI3K and Akt1 were detected by immunohistochemistry and real-time PCR, respectively. The contents of BALP and BGP in serum were detected by ELISA.
  
  
  RESULTS
  The rates of dental fluorosis in the fluorosis rats were increased, and the fluoride contents in bone and urine of the fluorosis rats were increased compared to the control group, the difference was statistically significant (P < 0.05). The bone trabeculae thickness and density and the thickness of bone cortex in fluorosis rats were remarkably increased, the space of bone trabeculae was reduced, and in accordance with the matching morphometrical indices, the difference was statistically significant (P < 0.05) as compared with the control rats. The contents of BALP [(54.61 ± 2.27) U/L] and BGP [(2.38 ± 0.16) µg/L]in the fluoride groups were higher than those in the control group, the difference was statistically significant (P < 0.05). Ultrastructurally, the broadening of the osseouslacuna was observed. The reduced protuberances of the osteocytes, the unclear organelle structure, pyknosis, karyotheca increasation and edged chromatin were also observed. Compared to the control group, the expressions of protein and its mRNA of p38, Osx, PI3K and Akt1 were higher in the fluorosis rats than those in the control rats, and the difference was statistically significant (P < 0.05). There is no any expression of p38, Osx, PI3K and Akt1 in the osteocytes in fluorosis rats.
  
  
  CONCLUSIONS
  The over-expression of p38, Osx, PI3K and Akt1 in bone tissue of fluorosis rats may relate to the accumulation of fluorine in the body. The bone injury mainly occur in the stage of the differentiation and proliferation. The upregulation of P38MARK signal path and PI3K/Akt1 signal path may be involved in the pathogenesis of bone injury caused by fluoride.
authors.affiliation: Department of Pathology, Guiyang Medical University, Guiyang, China.
authors.forename: Yan-ni
authors.initials: YN
authors.lastname: Yu
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.forename: Hai-zhen
authors.initials: HZ
authors.lastname: Zhu
authors.forename: Chao-nan
authors.initials: CN
authors.lastname: Deng
authors.forename: Zhi-zhong
authors.initials: ZZ
authors.lastname: Guan
mesh_terms: D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D005458:Fluoride Poisoning / Q000378:metabolism* / Q000473:pathology; D005459:Fluorides / Q000378:metabolism / Q000652:urine; D009050:Fluorosis, Dental / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D015675:Osteocalcin / Q000097:blood; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D012969:Sodium Fluoride / Q000633:toxicity; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000469:Alkaline Phosphatase; D005459:Fluorides; D015675:Osteocalcin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D012333:RNA, Messenger; D012969:Sodium Fluoride; D014157:Transcription Factors; D048051:p38 Mitogen-Activated Protein Kinases; C495181:Sp7 protein, rat