Antonio Casado-Díaz

Risedronate positively affects osteogenic differentiation of human mesenchymal stromal cells.

BACKGROUND AND AIMS Bisphosphonates are widely used for the treatment of bone pathologies, mainly due to their ability to inhibit osteoclastic activity and thus bone resorption. Yet, their potential effect on bone formation is unclear. Our aim was to determine whether risedronate can affect osteoblastic differentiation of mesenchymal stromal cells (MSC). METHODS We evaluated the effect of the risedronate, which is a bisphosphonate widely used in clinical settings, on the differentiation of precursor cells of osteoblasts and adipocytes. Thus, MSC from human bone marrow were induced to differentiate into osteoblasts or adipocytes in the presence or absence of two risedronate concentrations (10⁻⁸ M and 10⁻⁹ M). RESULTS Risedronate increased the levels of osteogenic markers including the extracellular matrix mineralization on cells induced to osteoblasts. On the other hand, such bisphosphonates did not have significant effects on the pparγ2 and lpl adipogenic genes or the fat vesicle accumulation on the cells induced into adipocytes. In addition, it increased the expression of early osteogenic differentiation genes like runx2 on MSC not induced to differentiate. CONCLUSIONS Risedronate concentrations used favor the osteogenic differentiation and the MSC commitment towards osteoblasts. This suggests the possibility of using this bisphosphonate in cyclic bone treatments with anabolic drugs, enhancing the effect of the latter via a previous MSC commitment to preosteoblasts.

Transcriptomic Analyses of Adipocyte Differentiation From Human Mesenchymal Stromal-Cells (MSC)

Adipogenesis is a physiological process required for fat‐tissue development, mainly involved in regulating the organism energetic‐state. Abnormal distribution‐changes and dysfunctions in such tissue are associated to different pathologies. Adipocytes are generated from progenitor cells, via a complex differentiating process not yet well understood. Therefore, we investigated differential mRNA and miRNA expression patterns of human mesenchymal stromal‐cells (MSC) induced and not induced to differentiate into adipocytes by next (second)‐generation sequencing. A total of 2,866 differentially expressed genes (101 encoding miRNA) were identified, with 705 (46 encoding miRNA) being upregulated in adipogenesis. They were related to different pathways, including PPARG, lipid, carbohydrate and energy metabolism, redox, membrane‐organelle biosynthesis, and endocrine system. Downregulated genes were related to extracellular matrix and cell migration, proliferation, and differentiation. Analyses of mRNA‐miRNA interaction showed that repressed miRNA‐encoding genes can act downregulating PPARG‐related genes; mostly the PPARG activator (PPARGC1A). Induced miRNA‐encoding genes regulate downregulated genes related to TGFB1. These results shed new light to understand adipose‐tissue differentiation and physiology, increasing our knowledge about pathologies like obesity, type‐2 diabetes and osteoporosis. J. Cell. Physiol. 232: 771–784, 2017.