Context-dependent roles of 11β-HSD1 in bone and skeletal muscle diseases

Bone and skeletal muscles are vital to human health, and diseases related to these tissues can place significant stress on patients, families, and society. The key enzyme regulating glucocorticoid metabolism, 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), is encoded by the HSD11B1 gene and can convert inactive cortisone into active cortisol. Recent studies have shown that 11β-HSD1 is a key enzyme in the pathogenesis of bone and skeletal muscle, with its function being strictly context-dependent. 11β-HSD1 inhibits osteoblast differentiation and activates osteoclast formation, contributing to glucocorticoid-induced osteoporosis (GIOP). 11β-HSD1 accelerates skeletal muscle atrophy by disrupting the stability of muscle proteins. It plays a dual role in anti-inflammation and bone protection, participating in polyarthritis; 11β-HSD1 also contributes to bone loss and anti-inflammation in rheumatoid arthritis (RA) through multiple pathways. Clarifying the context-specific mechanisms of 11β-HSD1 in bone and skeletal muscle diseases is critical for clinical translation. This review systematically summarizes the role of 11β-HSD1 in bone and skeletal muscle diseases, outlines its potential as a disease-specific therapeutic target, and provides new insights for precise treatment of these diseases.