Iron overload enhances human mesenchymal stromal cell growth And Hampers matrix calcification

Publication date: Available online 3 February 2016
Source:Biochimica et Biophysica Acta (BBA) - General Subjects
Author(s): Adriana Borriello, Ilaria Caldarelli, Maria Carmela Speranza, Saverio Scianguetta, Annunziata Tramontano, Debora Bencivenga, Emanuela Stampone, Aide Negri, Bruno Nobili, Franco Locatelli, Silverio Perrotta, Adriana Oliva, Fulvio Della Ragione
BackgroundIron overload syndromes include a wide range of diseases frequently associated with increased morbidity and mortality. Several organs are affected in patients with iron-overload including liver, heart, joints, endocrine glands and pancreas. Moreover, severe bone and hemopoietic tissue alterations are observed. Because of the role of bone marrow mesenchymal stromal cells (BM-MSCs) in bone turnover and hematopoiesis, iron effects on primary BM-MSCs cultures were evaluated.MethodsPrimary human BM-MSCs cultures were prepared and the effects of iron on their proliferation and differentiation were characterized by biochemical analyses and functional approaches.ResultsAddition of iron to the culture medium strongly increased BM-MSCs proliferation and induced their accelerated S-phase entry. Iron enters BM-MSCs through both transferrin-dependent and transferrin-independent mechanisms. Inducing the accumulation of cyclins E and A, the decrease of p27Kip1 and the activation of MAPK pathway. Conversely, neither apoptotic signs nor up-regulation of reactive oxygen species were observed. Iron inhibited both differentiation of BM-MSCs into osteoblasts and in vitro matrix calcification. These effects result from the merging of inhibitory activities on BM-MSCs osteoblastic commitment and on the ordered matrix calcification process.ConclusionsWe demonstrated that BM-MSCs are a target of iron overload. Iron accelerates BM-MSCs proliferation and affects BM-MSCs osteoblastic commitment, hampering matrix calcification.General SignificanceOur study reports, for the first time, that iron, at concentration found in overloaded patient sera, stimulates the growth of BM-MSCs, the BM multipotent stromal cell component. Moreover, iron modulates the physiological differentiation of these cells, affecting bone turnover and remodeling.



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