title: Influence of glucocorticoids on the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells.
abstract: BACKGROUND
  Glucocorticoid has been used extensively in clinical applications, because of its several pharmacologic actions, which include immunosuppression, anti-inflammation, anti-shock, and relief of asthma. However, the long-term or high-dose application of glucocorticoid can induce adverse effects such as osteoporosis, which is known in this case as glucocorticoid-induced osteoporosis (GIOP). It is a secondary osteoporosis that results in easy fracturing, and even disability. Therefore it became a thorny issue.
  
  
  METHODS
  The rat model of glucocorticoid-induced osteoporosis (GIOP) was replicated to isolate BMSCs. Rats were assigned into four groups: normal, normal induction, GIOP, and GIOP induction. The growth cycle was monitored by using flow cytometry. Osteogenic differentiation was compared by using alkaline phosphatase (ALP) staining with a modified calcium cobalt method. The quantitative detection of osteoprotegerin and the receptor activator of nuclear factor kappa-B ligand (RANKL) was conducted by using enzyme-linked immunoassay. Finally, renal Klotho mRNA expression was assessed by using RT-PCR.
  
  
  RESULTS
  BMSC proliferation was reduced in GIOP rats. The ALP-positive expression of normal BMSCs to the osteogenic induction solution was stronger than that of BMSCs from GIOP rats (P < 0.01). Osteoprotegerin expression was significantly higher in the normal induction group than in the normal, GIOP (P < 0.01), and GIOP induction groups (P < 0.05). RANKL expression was significantly higher in the normal induction group than in the other groups (P < 0.01) and significantly higher in the normal group than in the GIOP and GIOP induction groups (P < 0.01). RT-PCR analysis showed that renal Klotho mRNA expression was significantly reduced in the GIOP group compared with the normal group (P < 0.01).
  
  
  CONCLUSIONS
  BMSC proliferation, osteogenic differentiation, and reactive activity to an osteogenic inductor were reduced in GIOP rats. Klotho mRNA expression decreased during GIOP induction.
authors.forename: Da-An
authors.initials: DA
authors.lastname: Zhou
authors.forename: Hong-Xin
authors.initials: HX
authors.lastname: Zheng
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Wang
authors.forename: Dan
authors.initials: D
authors.lastname: Shi
authors.affiliation: Department of Spinal and Neural Function Reconstruction, School of Rehabilitation Medicine of Capital Medical University, China Rehabilitation Research Center, No, Jiaomeibei Road Fengtai District, Beijing 100068, China. dahxcn@yeah.net.
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Li
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D002454:Cell Differentiation; D002478:Cells, Cultured; D003907:Dexamethasone; D004195:Disease Models, Animal; D005260:Female; D005938:Glucocorticoids; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism; D000090265:Klotho Proteins; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D010012:Osteogenesis; D010024:Osteoporosis / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D005938:Glucocorticoids; D053244:Osteoprotegerin; D053245:RANK Ligand; C506032:Tnfrsf11b protein, rat; D003907:Dexamethasone; D000469:Alkaline Phosphatase; D005966:Glucuronidase; D000090265:Klotho Proteins