Enhanced osteogenic potential of periosteal stem cells maintained cortical bone relatively stable under microgravity

Abstract

Bone loss induced by microgravity was site-specific, which occurred in cortical bone later than in trabecular bone under microgravity. The mechanism of it still remains unclear. Periosteal stem cells (PSCs) are involved in periosteal bone formation and contributed to the development of cortical bone. However, whether the behavior of PSCs involved in preventing cortical bone loss under microgravity was unknown. In this study, the alterations of PSCs under simulated microgravity were investigated by in vivo and in vitro experiments respectively. Firstly, 8-weeks-old rats were tail-suspended for 21 days to simulate microgravity. The bone mineral density (BMD) and cortical bone morphometry of the tibia were examined by μCT, and the number of PSCs as well as bone formation-related factors (RUNX2, SP7, COL1A1) on the periosteal surface of tibia were examined by immunofluorescence. Secondly, the PSCs isolated from 7-days-old rats were cultured in 2D clinostat to simulate microgravity for 5 days. The expressions of osteogenesis-related (RUNX2, SP7, COL1A1, ALP, OCN, BMP2, OPN) and adipogenesis-related factors (PPARG, CEBPA) were determined by qRT-PCR. The in vivo results showed that unlike BMD in trabecular bone that decreased significantly, BMD in cortical bone did not change in the tibia of tail-suspended rats. What's more, there was no significant change in the cortical cross-sectional area. Meanwhile, the number of PSCs and osteoblasts, and the expression levels of RUNX2, SP7 and COL1A1 on the periosteal surface were all increased. As for the in vitro experiment, the expressions of osteogenesis-related factors (RUNX2, SP7, COL1A1, OCN, OPN, BMP2) in PSCs were increased, while the adipogenesis-related factors (PPARG, CEBPA) were decreased significantly. These results suggested that simulated microgravity could enhance the osteogenic potential of PSCs, which may contribute to maintain the cortical bone relatively stable.