Human parathyroid hormone could enhance hematopoiesis by activating insulin-like growth factor system rather than hematopoietic growth factors from osteoblasts.
Human parathyroid hormone could enhance hematopoiesis by activating insulin-like growth factor system rather than hematopoietic growth factors from osteoblasts.
Abstract
Purposes: Osteoblasts constitute part of the stromal system in marrow and produce a number of cytokines and insulin-like growth factors (IGFs) which could affect the survival and proliferation of progenitor cells. First, we observed the effect of human parathyroid hormone (hPTH) on the hematopoietic recovery in the mice with chronic bone marrow hypoplasia (CBMH) model. Then, we compared the expression of IGFs with that of hematopoietic growth factors to explore the possible mechanism of hPTH for hematopoiesis. Methods: We demonstrated the CBMH model in the mice with 10 doses of busulfan (9mg/kg/day), and then injected daily hPTH (40ug/kg/day) or vehicle intraperitoneally in the CBMH mice alternating weekly for 7 weeks. We compared the microarchtecture and hematopoietic cellularity between 2 groups. To reveal the possible mechanism of enhancing hematopoiesis by hPTH, human cord blood derived mesenchymal stem cells (hCB-MSC) were cultured and differentiated to osteoblasts in the osteogenic medium with or without hPTH (0, 10, 50, 100nM). The mRNA expressions of IGF-1,-2, IGF-binding protein (BP) 1,2,3 as well as of G-CSF, GM-CSF, IL-6, SDF-1 from the cultured osteoblasts were determined using RT-qPCR. Results: The hematopoietic cellularity and trabecular tunneling were increased in bone marrow of hPTH-treated mice compared with control mice. The mRNA expressions of IGF-2, IGF-BP 1,2 from osteoblasts were increased greater than in hCB-MSC, and also dramatically increased after treatment with 50 or 100nM of hPTH, respectively. Although the G-CSF, GM-CSF, IL-6, and SDF-1 were expressed in osteoblasts, the mRNA levels of these hematopoietic growth factors were not significantly affected by hPTH. Conclusions: hPTH enhanced the hematopoietic activity in the CBMH mice and dramatically increased the expression level of IGF system from osteoblasts. Therefore, the activation of IGF system rather than of hematopoietic growth factors could be an important factor for enhancing the survival and proliferation of hematopoietic stem cells by increasing the functions of osteoblasts with hPTH.