Frontiers in Cell and Developmental Biology · Apr 20, 2026

Ubiquitin-proteasome system regulation of bone remodeling in postmenopausal osteoporosis

By Chen X, Zhao T, Zhou H et al.

Postmenopausal osteoporosis (PMOP) is associated with declining estrogen levels, and this hormonal deficiency alters the physiological balance between bone formation and resorption. Substantial evidence indicates that protein homeostasis disorders play a significant role in the pathological process of PMOP. As the core system regulating protein homeostasis, the ubiquitin-proteasome system exerts crucial regulatory effects on bone metabolism under estrogen-deficient conditions. Abnormal activity of these ubiquitin-associated enzymes often leads to excessive degradation or abnormal accumulation of key regulatory proteins in bone metabolism, thereby exacerbating bone loss in PMOP. This review summarizes recent studies, focusing on how ubiquitin E3 ligases and deubiquitinating enzymes influence the function of osteoblasts and osteoclasts in PMOP. By synthesizing evidence from postmenopausal clinical samples and ovariectomized animal models, we further elucidate the specific roles of ubiquitin-related pathways in this disease. A deeper understanding of the mechanisms underlying UPS dysregulation in postmenopausal women holds promise for identifying novel molecular targets for future therapeutic strategies in PMOP.

doi.org/10.3389/fcell.2026.1788812Open accessPubMed 42089111Mechanisms