关键词: Bone loss Different duration Hindlimb disuse RNA-seq

Mesh : Animals Hindlimb Suspension Mice Homeostasis Osteogenesis / genetics Male Mice, Inbred C57BL X-Ray Microtomography Osteoporosis / genetics Bone and Bones / metabolism Bone Density Hindlimb

来  源:   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.
摘要:
废用性骨质疏松症是长期航天和卧床不起的宇航员常见的骨骼健康问题之一。然而,这种机械卸载导致骨丢失的潜在机制尚未完全了解。在这项研究中,我们采用不同尾部悬吊长度的后肢卸载小鼠模型,研究在不同的废用时间下,骨丢失是否受不同因素的调节。我们的显微CT结果显示,与1W尾悬吊小鼠相比,6W尾悬吊小鼠的骨量下降更明显。如BV/TV的更大降低所示,TB。N,B.Ar/T.Ar和CTTh.RNA测序结果显示,后肢废用对细胞运动和免疫系统过程有显著影响,可导致骨丢失。实时定量PCR结果表明,与长期悬尾小鼠相比,短期悬尾小鼠中下调的骨形成相关基因数量更多。是的,因此,表明,虽然持续的后肢卸载持续导致骨丢失,在此过程中,骨稳态的分子调节趋于达到平衡。
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