{Reference Type}: Journal Article {Title}: Different impact of short-term and long-term hindlimb disuse on bone homeostasis. {Author}: Gao M;Dong C;Chen Z;Jiang R;Shaw P;Gao W;Sun Y; {Journal}: Gene {Volume}: 918 {Issue}: 0 {Year}: 2024 Aug 5 {Factor}: 3.913 {DOI}: 10.1016/j.gene.2024.148457 {Abstract}: Disuse osteoporosis is one of the major problems of bone health which commonly occurs in astronauts during long-term spaceflight and bedridden patients. However, the mechanisms underlying such mechanical unloading induced bone loss have not been fully understood. In this study, we employed hindlimb-unloading mice models with different length of tail suspension to investigate if the bone loss was regulated by distinct factors under different duration of disuse. Our micro-CT results showed more significant decrease of bone mass in 6W (6-week) tail-suspension mice compared to the 1W (1-week) tail-suspension ones, as indicated by greater reduction of BV/TV, Tb.N, B.Ar/T.Ar and Ct.Th. RNA-sequencing results showed significant effects of hindlimb disuse on cell locomotion and immune system process which could cause bone loss.Real-time quantitative PCR results indicated a greater number of bone formation related genes that were downregulated in short-term tail-suspension mice compared to the long-term ones. It is, thus, suggested while sustained hindlimb unloading continuously contributes to bone loss, molecular regulation of bone homeostasis tends to reach a balance during this process.