miR-22 Inhibits CD34⁺ Cell Expansion Through Decreasing β-Catenin in Osteoblasts

The bone marrow (BM) microenvironment, heavily composed of osteoblasts, plays a key role during the normal development of hematopoiesis. Endogenous miR-22 has an important function in the hematopoietic development and osteoblastic differentiation. It is unclear whether miR-22 in osteoblasts from the BM microenvironment also has an important function in the development of hematopoiesis. This study found that the capacity of hTERT-transduced fetal bone marrow osteoblasts (FBMOB-hTERT) cells to expand human cord blood (CB) CD34⁺ cells and maintain the multipotency of CB CD34⁺ cells is decreased upon ectopic expression of miR-22. Further experiments revealed that with the existence of CB CD34⁺ cells, the expression of β-catenin in FBMOB-hTERT cells is decreased upon ectopic expression of miR-22. The reduced ability of FBMOB-hTERT cells to expand human CB CD34⁺ cells and maintain the multipotency of CB CD34⁺ cells upon ectopic miR-22 was partly rescued by overexpression of β-catenin. The study indicated that the ability of osteoblasts to expand human CB CD34⁺ cells and maintain the multipotency of CB CD34⁺ cells is decreased upon ectopic expression of miR-22. The decreased expression of β-catenin is, at least partly, responsible for the reduced ability of osteoblasts for expanding and supporting CB CD34⁺ cells upon ectopic expression of miR-22.