Studio delle cellule staminali mesenchimali in pazienti osteoporotici mediante analisi di espressione genica durante il differenziamento osteoblastico

Data inizio
1 ottobre 2007
Durata (mesi) 
24
Responsabili (o referenti locali)
Dalle Carbonare Luca Giuseppe

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.
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.
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.
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.

Enti finanziatori:

Società italiana dell'osteoporosi del metabolismo minerale e delle malattie dello scheletro
Finanziamento: assegnato e gestito dal Dipartimento

Partecipanti al progetto

Francesco Bertoldo
Professore associato
Luca Giuseppe Dalle Carbonare
Professore associato
Luca Donatelli
Pubblicazioni
Titolo Autori Anno
Circulating mesenchymal stem cells with abnormal osteogenic differentiation in patients with osteoporosis. Dalle Carbonare L; Valenti MT; Zanatta M; Donatelli L; Lo Cascio V. 2009
Gene expression analysis in osteoblastic differentiation from peripheral blood mesenchymal stem cells. Valenti MT; Dalle Carbonare L; Donatelli L; Bertoldo F; Zanatta M; Lo Cascio V. 2008

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