Ubiquitin proteasome system was found to contribute to bone loss by regulating bone turnover and metabolism, by modulating osteoblast differentiation and bone formation as well as formation of osteoclasts that contribute to bone resorption. Muscle Ring Finger (MuRF) are novel ubiquitin ligases, which are muscle specific and have not been much implicated in the bone but have been implicated in several human diseases including heart failure and skeletal muscle atrophy. This study is aimed at understanding the role of MuRF1, MuRF2, MuRF3 and Atrogin which are distinct MuRF family proteins in bone homeostasis. Wildtype, heterozygous and homozygous mice of each of the isoforms were used and the bone microarchitecture and mechanical properties were assessed using microCT and biomechanics. MuRF1 depletion was found to alter cortical properties in both males and females, but only trabecular spacing in the females. MuRF2 depletion let to no changes in the cortical and trabecular properties but change in the strain to yield in the females. Depletion of MuRF3 led to decrease in the cortical properties in the females and increase in the trabecular properties in the males. Atrogin depletion was found to reduce cortical properties in both males and females, whereas some trabecular properties were found to be reduced in the females. Each muscle-specific ligase was found to alter the bone structure and mechanical properties in a distinct a sex-dependent manner.

发现泛素蛋白酶体系统通过调节骨转换和代谢、调节成骨细胞分化和骨形成以及有助于骨吸收的破骨细胞的形成来促进骨丢失。肌肉环指 (MuRF) 是新型泛素连接酶，它是肌肉特异性的，与骨骼的关系不大，但与包括心力衰竭和骨骼肌萎缩在内的几种人类疾病有关。本研究旨在了解 MuRF1、MuRF2、MuRF3 和 Atrogin 这些不同的 MuRF 家族蛋白在骨稳态中的作用。使用每种同种型的野生型、杂合子和纯合子小鼠，并使用 microCT 和生物力学评估骨微结构和机械性能。发现 MuRF1 耗竭会改变男性和女性的皮质特性，但只会改变女性的小梁间距。MuRF2 的消耗使皮质和小梁特性没有变化，但在雌性中产生的应变发生变化。MuRF3 的消耗导致女性的皮质特性降低，而男性的小梁特性增加。发现 Atrogin 消耗会降低男性和女性的皮质特性，而发现女性的一些小梁特性会降低。发现每种肌肉特异性连接酶以不同的性别依赖性方式改变骨骼结构和机械性能。MuRF2 的消耗使皮质和小梁特性没有变化，但在雌性中产生的应变发生变化。MuRF3 的消耗导致女性的皮质特性降低，而男性的小梁特性增加。发现 Atrogin 消耗会降低男性和女性的皮质特性，而发现女性的一些小梁特性会降低。发现每种肌肉特异性连接酶以不同的性别依赖性方式改变骨骼结构和机械性能。MuRF2 的消耗使皮质和小梁特性没有变化，但在雌性中产生的应变发生变化。MuRF3 的消耗导致女性的皮质特性降低，而男性的小梁特性增加。发现 Atrogin 消耗会降低男性和女性的皮质特性，而发现女性的一些小梁特性会降低。发现每种肌肉特异性连接酶以不同的性别依赖性方式改变骨骼结构和机械性能。