Ubiquitin‐specific peptidases: Players in bone metabolism

Abstract

Osteoporosis is an ageing‐related disease, that has become a major public health problem and its pathogenesis has not yet been fully elucidated. Substantial evidence suggests a strong link between overall age‐related disease progression and epigenetic modifications throughout the life cycle. As an important epigenetic modification, ubiquitination is extensively involved in various physiological processes, and its role in bone metabolism has attracted increasing attention. Ubiquitination can be reversed by deubiquitinases, which counteract protein ubiquitination degradation. As the largest and most structurally diverse cysteinase family of deubiquitinating enzymes, ubiquitin‐specific proteases (USPs), comprising the largest and most structurally diverse cysteine kinase family of deubiquitinating enzymes, have been found to be important players in maintaining the balance between bone formation and resorption. The aim of this review is to explore recent findings highlighting the regulatory functions of USPs in bone metabolism and provide insight into the molecular mechanisms governing their actions during bone loss. An in‐deep understanding of USPs‐mediated regulation of bone formation and bone resorption will provide a scientific rationale for the discovery and development of novel USP‐targeted therapeutic strategies for osteoporosis.

Advanced Skeletal Ossification Is Associated with Genetic Variants in Chronologically Young Beef Heifers

“…The SNP_ 25:38,081,982 is near the genes USP42 and ANKRD61. The USP family plays an empirical role in posttranslational modification and protein homeostasis by regulating cellular activity [ 75 ]. USP proteins are involved in aspects of bone growth as identified in humans and mice [ 76 , 77 , 78 , 79 , 80 , 81 ].…”

“…Both genes influence or regulate ubiquitylation. Ubiquitin is a regulatory protein important in cell signaling [ 75 , 76 ], including bone cells, as ubiquitin-dependent endocytosis is required to remove the receptors on the surface. This includes receptors that bind bone morphogenic proteins (BMP).…”

Icariin promotes osteogenic differentiation of human bone marrow mesenchymal stem cells by regulating USP47/SIRT1/Wnt/β‐catenin

“…Ubiquitin‐specific peptidases (USPs) are major members of the deubiquitinating enzyme family (Shen et al., 2023; Young et al., 2019), and are capable of recognizing the ubiquitination signals of specific proteins to deubiquitinate the target proteins (Fu et al., 2023). Previous study found that USP47 promoted osteogenic transdifferentiation to mediate vascular calcification in chronic kidney disease (Xiao et al., 2022).…”