Epoetin-alfa-induced osteogenesis in the bone organoid model

Introduction: Erythropoietin interacts ETwith EPOR/βcR(CD131) and activates the non-canonical pathway JAK/STAT and PI3K/AKT. Phosphorylated STAT subunits were found to get dimerized and translocated into the nucleus to activate the expression of the Runx-2 and TGF-β genes. The purpose of the study was to evaluate the effectiveness of osteogenesis when using epoetin alpha as an osteoinducer in an experimental model of a bone organoid. Materials and Methods: The study was conducted on human mesenchymal stem cells (hMSC) and trabecular bone organoids (TBO). Photometry and microscopy were used to assess the effects of drugs on proliferation and differentiation of hMSС and the formation of osteogenic tissue in TBO. The volume of connective tissue structures and the activity of mitochondria was determined in cells that form fibrovascular osteogenic tissue in TBO. Results: Epoetin alpha was found to have a dose-dependent osteoinductive effect in TBO. At a dose of 200 IU/mL, epoetin alpha has an inhibitory effect, whereas at a dose of 20 IU/mL, it activates the proliferation and differentiation of hMSC in the osteogenic direction by inducing osteogenesis in TBO. Conclusion: Epoetin alpha has a protective effect on osteogenesis in TBO inducing the proliferation of osteoblasts and endotheliocytes, stimulating the growth of connective tissue structures of the bone organoid with the formation of osteogenic tissue along with increasing the activity of mitochondria and reducing intracellular generation of reactive oxygen species.