Reduction in osteogenic commitment of mesenchymal stem cells from thalassemic patients

Abstract

Osteoporosis is presented in severe thalassemia due ineffective in erythropoiesis. More than 15-20 times comparing to normal individual expansion of bone marrow causes bone loss and osteoporosis. The patients may be suffered from bone change depending on the degree of osteoporosis. Osteoblasts are originate from mesenchymal stem cells, which have the capacity to differentiate into osteoblast, adipocytes, chondrocytes, myoblasts or fibroblast. The commitment proliferation and differentiation of mesenchymal stem cells are regulated by multiple factors, including cytokines, growth factors, systemic hormones and transcription regulators. Bone marrow cells are responsible for the production of many paracrine and autocrine bone regulatory factors and the stromal cells population are essential for normal bone formation. Hence, we hypothesize that bone marrow expansion may interrupt on mesenchymal stem cells differentiate into bone cells that lead to osteoporosis in severe thalassemic patients. Thus, in this study we investigate the expression level of a transcription factor genes and bone differentiation genes for mesenchymal stem cells in severe thalassemic patients compare with normal by using relative quantification real time RT-PCR. Our data show that the expression of Cbfa1, Osterix, BMP-2, Collagen type I, Alkaline phosphatase, Osteocalcin was downregulated in MSCs from the patients. In addition the expression of Cbfa1, Osterix, Osteocalcin was downregulated in HSCs from the patients. Interestingly, the mRNA of PPAR[gamma]2 was not detected from both of mesenchymal stem cells and hematopoietic stem cells from healthy donor and thalassemic patients. Moreover, the mRNA of BMP-2, Alkaline Phosphatase was not detected from hematopoietic stem cells. In conclusion, the expansion of bone marrow interrupt MSCs differentiation by downregulate expression of transcription factor genes and bone differentiation genes.