title: Circulating mesenchymal stem cells with abnormal osteogenic differentiation in patients with osteoporosis.
abstract: OBJECTIVE
  While the role of osteoclasts in bone loss has been well investigated, the involvement of osteoblast-lineage cells has not been completely elucidated. Several genes contribute to normal osteoblastic differentiation from mesenchymal stem cells (MSCs), but an understanding of their role in the pathogenesis of osteoporosis is still lacking. The present study was undertaken to evaluate a possible alteration of osteogenic gene expression as a mechanism contributing to bone loss.
  
  
  METHODS
  We studied the osteogenic differentiation process in MSCs obtained from the peripheral blood of 31 patients with osteoporosis and 20 normal donors. The cells were evaluated by colony-forming unit-fibroblastic assay and cultured in osteogenic medium to analyze the transcription factors runt-related transcription factor 2 (RUNX-2) and Sp7 and the bone-related genes COL1A1, SPARC, and SPP1 after 3, 8, and 15 days of differentiation. In addition, to determine possible differences between the 2 groups in terms of osteoclastic and osteoblastic activation, we quantified the osteoprotegerin (OPG) and RANKL levels in the supernatants of osteoblastic culture.
  
  
  RESULTS
  Circulating MSCs were increased in osteoporosis patients compared with normal donors. In contrast, gene expression analysis revealed down-regulation of RUNX2, Sp7, COL1A1, SPARC, and SPP1 in patients with osteoporosis, associated with a lower OPG:RANKL ratio.
  
  
  CONCLUSIONS
  These results suggest that an alteration of osteoblastic differentiation may contribute to the pathogenesis of osteoporosis. The noninvasive approach used in the present study could be proposed as a useful tool for studying mesenchymal involvement in bone diseases.
authors.affiliation: University of Verona, Verona, Italy. luca.dallecarbonare@univr.it
authors.forename: Luca
authors.initials: L
authors.lastname: Dalle Carbonare
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Valenti
authors.forename: Mirko
authors.initials: M
authors.lastname: Zanatta
authors.forename: Luca
authors.initials: L
authors.lastname: Donatelli
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Lo Cascio
mesh_terms: D000368:Aged; D001862:Bone Resorption / Q000503:physiopathology; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology*; D010012:Osteogenesis / Q000502:physiology*; D015676:Osteonectin / Q000378:metabolism; D053495:Osteopontin / Q000378:metabolism; D015663:Osteoporosis, Postmenopausal / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D053244:Osteoprotegerin / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism; D000076182:Sp7 Transcription Factor; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D050659:Core Binding Factor Alpha 1 Subunit; D015676:Osteonectin; D053244:Osteoprotegerin; D053245:RANK Ligand; C506895:SPP1 protein, human; D000076182:Sp7 Transcription Factor; C478163:SP7 protein, human; D014157:Transcription Factors; D053495:Osteopontin