We recently reported the isolation of a unique subpopulation of @entity1 stromal cells from bone marrow (BM) termed marrow-isolated adult multilineage inducible (MIAMI) cells, capable of differentiating in vitro into mature-like cells from all three germ layers. The @entity26 tension ( @entity4095 ) in BM ranges from 1 to 7%, which prompted us to examine the role of @entity4095 in regulating the capacity of MIAMI cells both to self-renew and maintain their pluripotentiality ( @entity3308 ) or to progress toward osteoblastic differentiation. MIAMI cells were grown under low- @entity4095 conditions (1, 3, 5, and 10% @entity26 ) or air (21% @entity26 ). The proliferation rate of cells exposed to 3% @entity26 (3 days) increased, resulting in cell numbers more than threefold higher than those of cells exposed to air (at 7 days). In cells grown under osteoblastic differentiation conditions, the expression of the osteoblastic markers osteocalcin, bone sialoprotein, @entity8088 , and @entity8087 and alkaline phosphatase activity was upregulated when incubated in air; however, it was blocked at low (3%) @entity4095 . Similarly, biomineralization of long-term cell cultures was high under osteoblastic differentiation conditions in air but was undetectable at low (3%) @entity4095 . In contrast, low @entity4095 upregulated mRNAs for @entity4729 , @entity21547 , telomerase reverse transcriptase, and @entity519 -inducible factor-1 alpha, and increased the expression of SSEA-4 compared to air. Moreover, the expression of embryonic stem cell markers was sustained even under osteogenic culture conditions. Similar results were obtained using commercially available marrow stromal cells. We hypothesize a physiological scenario in which primitive MIAMI cells self-renew while localized to areas of low @entity4095 in the bone marrow, but tend to differentiate toward osteoblasts when they are located closer to blood vessels and exposed to higher @entity4095 . Our results strongly suggest that maintaining developmentally primitive @entity1 cells in vitro at low @entity4095 would be more physiological and favor @entity3308 over differentiation.

Low XXXX tension inhibits osteogenic differentiation and enhances @entity3308 of @entity1 MIAMI cells.

@entity1 :: ('9606', 'Species') :: ['human'] @entity8088 :: ('121340', 'Gene') :: ['osterix'] @entity8087 :: ('860', 'Gene') :: ['Runx2'] @entity3308 :: ('MESH:D020295', 'Disease') :: ['stemness'] @entity4729 :: ('5460', 'Gene') :: ['OCT-4'] @entity21547 :: ('57455', 'Gene') :: ['REX-1'] @entity26 :: ('MESH:D010100', 'Chemical') :: ['oxygen'] @entity519 :: ('MESH:D000860', 'Disease') :: ['hypoxia'] @entity4095 :: ('MESH:C093415', 'Chemical') :: ['pO2']
@entity26 :: (MESH:D010100,Chemical) :: ['oxygen']
