title: G-CSF/SCF exert beneficial effects via anti-apoptosis in rabbits with steroid-associated osteonecrosis.
abstract: OBJECTIVE
  Osteonecrosis is also known as avascular necrosis, and two types of cell death are included in the pathogenesis of osteonecrosis: necrosis and apoptosis. Apoptosis in the osteonecrosis of femoral head is thought to be the key determinant of glucocorticoid-induced cortical bone loss. The present study was implemented to evaluate the anti-apoptotic effect of Granulocyte colony-stimulating factor and stem cell factor (G-CSF/SCF) in rabbits with steroid-induced osteonecrosis.
  
  
  METHODS
  In the experiment, osteonecrosis was induced by low-dose lipopolysaccharide and subsequent pulsed high-dose methylprednisolone. Rabbits in preventive medicine group were treated with 100 μg/kg/d G-CSF and 25 μg/kg/d SCF. Then hematological and histomorphometric methods were used to investigate the treatment effects of osteonecrosis. Apoptosis was assessed via quantitative TUNEL staining and activated caspase-3 immunostaining and immunoblotting.
  
  
  RESULTS
  The results showed that G-CSF/SCF treatment could increase the secretion of serum osteocalcin, but inhibit the expression of serum tartrate-resistant acid phosphatase (TRAP5b). The incidence of osteonecrosis was significantly decreased in Preventive group when compared with Steroid group (42.1% vs. 88.2%). Histomorphometric analysis showed that G-CSF/SCF pre-disposal treatment was able to increase trabecular mineral appositional rate (MAR) and bone formation rate (BFR). Quantitative TUNEL and activated caspase-3 levels showed lower apoptosis in the Preventive group.
  
  
  CONCLUSIONS
  In conclusion, G-CSF/SCF treatment could inhibit caspase-3-dependent apoptosis in osteocytes to exert beneficial effects in preventing steroid-induced ON in rabbit models.
authors: Department of Orthopaedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. wuxinghuo_71@yahoo.com.cn
authors: Xinghuo
authors: X
authors: Wu
authors: Shuhua
authors: S
authors: Yang
authors: Hong
authors: H
authors: Wang
authors: Chunqing
authors: C
authors: Meng
authors: Weihua
authors: W
authors: Xu
authors: Deyu
authors: D
authors: Duan
authors: Xianzhe
authors: X
authors: Liu
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000097:blood; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology* / Q000627:therapeutic use; D007527:Isoenzymes / Q000097:blood; D008775:Methylprednisolone; D015675:Osteocalcin / Q000097:blood; D010012:Osteogenesis / Q000187:drug effects; D010020:Osteonecrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000517:prevention & control*; D011817:Rabbits; D019089:Stem Cell Factor / Q000494:pharmacology* / Q000627:therapeutic use; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D007527:Isoenzymes; D019089:Stem Cell Factor; D015675:Osteocalcin; D016179:Granulocyte Colony-Stimulating Factor; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D053148:Caspase 3; D008775:Methylprednisolone