The role of galectin-3 in bone homeostasis: A review

The skeletal system maintains a delicate balance known as bone homeostasis, which is essential for the lifelong preservation of bone mass, shape, and integrity. This equilibrium relies on a complex interplay between bone marrow mesenchymal stem cells (BMSCs), osteoblasts, osteocytes, and osteoclasts. Galectin-3 (Gal-3), a chimeric galectin with a unique N-terminal tail and a conserved carbohydrate recognition domain (CRD) at its C-terminus, has emerged as a critical regulator in bone homeostasis. The CRD of Gal-3 mediates carbohydrate binding, while its N-terminal tail is implicated in oligomerization and phase separation, which are vital for its functionality. Gal-3's multivalency is central to its role in a range of cellular activities, including inflammation, immune response, apoptosis, cell adhesion, migration, and signaling-processes that are integral to bone remodeling. Imbalances in bone homeostasis often arise from disruptions in osteoblast differentiation and activity, increased osteoclast differentiation and activity. Gal-3's influence on these processes suggests its significant role in the regulation of bone remodeling. This review will examine the molecular mechanisms through which Gal-3 contributes to bone remodeling and discuss its potential as a therapeutic target for the treatment of bone-related disorders.