title: iNOS expression and osteocyte apoptosis in idiopathic, non-traumatic osteonecrosis.
abstract: OBJECTIVE
  Non-traumatic osteonecrosis is a progressive disease with multiple etiologies. It affects younger individuals more and more, often leading to total hip arthroplasty. We investigated whether there is a correlation between inducible nitric oxide synthase (iNOS) expression and osteocyte apoptosis in non-traumatic osteonecrosis.
  
  
  METHODS
  We collected and studied 20 human idiopathic, non-traumatic osteonecrosis femoral heads. Subchondral bone samples in the non-sclerotic region (n = 30), collected from osteoarthritis patients, were used as controls. Spontaneously hypertensive rats were used as a model for osteonecrosis in the study. We used scanning electron microscopy, TUNEL assay, and immunohistochemical staining to study osteocyte changes and apoptosis.
  
  
  RESULTS
  The morphology of osteocytes in the areas close to the necrotic region changed and the number of apoptotic osteocytes increased in comparison with the same region in control groups. The expression of iNOS and cytochrome C in osteocytes increased while Bax expression was not detectable in osteonecrosis samples. Using spontaneously hypertensive rats, we found a positive correlation between iNOS expression and osteocyte apoptosis in the osteonecrotic region. iNOS inhibitor (aminoguanidine) added to the drinking water for 5 weeks reduced the production of iNOS and osteonecrosis compared to a control group without aminoguanidine.
  
  
  CONCLUSIONS
  Our findings show that increased iNOS expression can lead to osteocyte apopotosis in idiopathic, non-traumatic osteonecrosis and that an iNOS inhibitor may prevent the progression of the disease.
authors.affiliation: Department of Orthopedics , the Second Xiangya Hospital, Central South University, Changsha, Hunan Province , China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Ali
authors.initials: A
authors.lastname: Kalhor
authors.forename: Shifeier
authors.initials: S
authors.lastname: Lu
authors.forename: Ross
authors.initials: R
authors.lastname: Crawford
authors.forename: Jiang-Dong
authors.initials: JD
authors.lastname: Ni
authors.forename: Yin
authors.initials: Y
authors.lastname: Xiao
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005270:Femur Head / Q000187:drug effects / Q000473:pathology*; D005271:Femur Head Necrosis / Q000201:enzymology* / Q000473:pathology; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010011:Osteocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D010020:Osteonecrosis / Q000201:enzymology / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D004791:Enzyme Inhibitors; D006146:Guanidines; D045304:Cytochromes c; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C004479:pimagedine