Roles of Wnt/β-Catenin Signaling in Osteoporosis, Disease Pathogenesis, and Natural Compound Intervention

Osteoblasts primarily originate from mesenchymal stem cells (MSCs) within the bone marrow. These stem cells possess the ability to differentiate into osteoblasts, which are responsible for secreting bone matrix, promoting bone formation, and contributing to bone remodeling. Dysfunction in osteoblast activity can lead to various bone-related disorders, such as osteoporosis, delayed fracture healing, and skeletal deformities. In recent years, due to the adverse effects associated with the use of parathyroid hormone (PTH) analogs, bisphosphonates, and calmodulin-targeting drugs, there has been growing interest in exploring the mechanisms underlying osteoblast differentiation. Researchers are increasingly focusing on identifying natural compounds as potential treatments for osteoporosis. Among the signaling pathways involved, the Wnt/β-catenin pathway is recognized as a key regulator of osteoblast differentiation and a crucial therapeutic target in osteoporosis. However, both upregulation and downregulation of this pathway have been implicated in various diseases, including cancers. This review highlights the role of the Wnt/β-catenin signaling pathway in osteoblast differentiation, examines the association between pathway-related proteins and human diseases, and summarizes recent advancements in the development of natural compounds targeting this pathway for osteoporosis therapy.