Abstract
Osteolytic diseases are a significant and escalating global public health issue, driven by the acceleration of population aging and the rising incidence of degenerative, metabolic, and neoplastic diseases. The primary therapeutic strategy for osteolytic diseases is to suppress the bone resorption activity of osteoclasts. Dusp1 is a member of the serine/threonine inducible nuclear phosphatase family and has significant anti-inflammatory effects. In this study, Dusp1 overexpression was induced via lentiviral transfection. We found that Dusp1 antagonized RANKL stimulation, mediated the MAPK signaling pathway, and downregulated the key downstream transcription factors c-FOS and NFATc1, thereby reducing the expression of osteoclast-specific genes. Furthermore, Dusp1 reduced the number and activity of osteoclasts both in vivo and in vitro, leading to a diminished bone resorption function. In addition, the results of animal experiments demonstrated that Dusp1 protected mice from LPS-induced skull osteolysis. Overall, our study reveals that Dusp1 suppresses osteoclast formation and activity by downregulating the MAPK/c-FOS/NFATc1 signaling pathway. These findings suggest the potential of Dusp1 to protect against osteolytic diseases.