Osteoporosis is a common skeletal disease with marked bone loss, deterioration of the bone microstructure and bone fragility. An abnormal bone remodelling cycle with relatively increased bone resorption is the crucial pathophysiological mechanism. Bone remodelling is predominantly controlled by osteoblasts and osteoclasts, which are specialized cell types that are regulated by a variety of osteogenic and osteoclastic factors, including cytokines expressed within the bone microenvironment under local or systemic inflammatory conditions. Signal transducer and activator of transcription 3 (STAT3) plays a prominent role in the communication between cytokines and kinases by binding downstream gene promotors and is involved in a wide range of biological or pathological processes. Emerging evidence suggests that STAT3 and its network participate in bone remodelling and the development of osteoporosis, and this factor may be a potent target for osteoporosis treatment. This review focuses on the role and molecular mechanism of the STAT3 signalling pathway in osteogenesis, osteoclastogenesis and osteoporosis, particularly the bone-related cytokines that regulate the osteoblastic differentiation of bone marrow stromal cells and the osteoclastic differentiation of bone marrow macrophages by initiating STAT3 signalling. This review also examines the cellular interactions among immune cells, haematopoietic cells and osteoblastic/osteoclastic cells.
Carnosine is a vital endogenous dipeptide that has anti-inflammatory, antiaging, anti-crosslinking, antitumor and immune regulatory effects. Numerous cell and animal model studies have proved that carnosine and its compounds promote the proliferation and differentiation of osteoblasts, inhibit osteoclasts and protect chondrocytes. They also regulate the cell cycle of bone progenitor cells and the differentiation of bone marrow mesenchymal stem cells, accelerate fracture healing, delay bone tumor development and ameliorate osteopenia induced by estrogen deficiency or disuse. The correlations between carnosine and activation signal molecules, pluripotent differentiation of bone marrow mesenchymal stem cells and interaction between bone cells are unclear. However, studies have proved that carnosine and its compounds have benefits in preventing and treating specific bone diseases. This makes them potential agents for the treatment of osteoporosis and bone tumors. The present review summarized the existing research on carnosine and its compounds in bone cells and tissue. It focused on the physiological function of carnosine and its compounds in the bone and their effect on bone metabolism-related diseases, thus providing support for developing new strategies for targeted therapy.
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