ECTS2014 Poster Presentations Cell biology: osteoblasts and bone formation (48 abstracts)
Inhibitory effect of GH on the adipogenic commitment of mesenchymal stromal cells derived from human trabecular bone
Simona Bolamperti 1 , Alice Spinello 1 , Aisha Sauer 3 , GianLuigi Moro 2 , Marco Ometti 2 , Gianfranco Fraschini 2 , Francesca Guidobono 4 , Alessandro Rubinacci 1 & Isabella Villa 1
1San Raffaele Scientific Institute, Bone Metabolism Unit, Milano, Italy; 2San Raffaele Scientific Institute, Orthopedic Unit, Milano, Italy; 3San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), Milano, Italy; 4University of Milano, Milano, Italy.
Besides its well known effect on longitudinal bone growth, GH plays a role in the maintenance of adult bone mass. As aging progresses GH levels decline, bone mass decreases and mesenchymal precursors show a reduced osteogenic differentiation capacity resulting in an increase in bone marrow adipocytes. We investigated the effect of GH on MSC differentiation and the possible involvement of microRNA in this process. Human MSC derived from trabecular specimens, waste material of orthopedic surgery (protocol approved by the Institutional Ethical Committee), were characterized by FACS analysis and cultured for 14 days in both normal growth and adipogenic medium in the presence or absence of GH (5 ng/ml). RT-PCR showed that in hMSCs cultivated in normal growth medium, GH enhances the expression of the osteogenic-related genes Runx2, although not significantly, osteoprotegerin (OPG, P<0.05) and osterix (OSX, P<0.05) and reduces the expression of the Wnt inhibitor DKK1, without any modulation of the adipogenesis related-genes adiponectin and C/EBPα. Since miR22 targets a Runx2 inhibitor and miR29c regulates DKK1 expression we evaluated the levels of miR22 and miR29c. Results showed that GH exposure induces an increase in both miRNAs.
In hMSCs cultivated in adipogenic medium GH does not increase the expression of the osteogenic genes OPG and OSX, but decreases adiponectin (P<0.01) and C/EBPα (P<0.01) expression. GH also downregulates miR-204 (P<0.05), which is known to be involved in adipogenesis. OilRedO staining of hMSCs confirmed these data showing that GH treatment significantly reduces lipid droplets formation (P<0.001).
Taken together these data suggest that GH plays a role in MSCs differentiation by increasing osteoblastogenesis in normal conditions. Moreover it might reverse MSCs commitment towards fat tissue in an adipogenic environment, such as the bone marrow milieu during the aging process.
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Bone Abstracts
ISSN 2052-1219 (online)
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