MiR-1a-3p/Fcgr4-dependent osteoclast activation regulates pathological bone loss

IntroductionOsteoporosis is a systemic metabolic disease characterized by disrupted homeostasis between osteoclast-mediated bone resorption and osteoblast-mediated bone formation. Accumulating evidence indicates that chronic systemic pathological states can exert sustained effects on osteo-immune homeostasis.

However, how these disturbances promote immune-mediated osteoclast dysregulation remains unclear.MethodsCandidate miRNAs targeting Fcgr4 were identified using bioinformatic prediction tools, and the direct interaction between miR-1a-3p and Fcgr4 was validated by dual-luciferase reporter assay. RAW264.7 cells were transfected with miR-1a-3p mimics or inhibitors to assess the effects of miR-1a-3p on osteoclast, which was evaluated by tartrate-resistant acid phosphatase (TRAP) staining, RT-qPCR, and Western blotting.

miR-1a-3p expression was further analyzed in human osteoporosis cohorts and animal models of bone loss. Furthermore, to investigate whether systemic psychological stress—a chronic pathological state with sustained immunoregulatory consequences—regulates this axis, a chronic unpredictable mild stress (CUMS) model was established to examine stress-associated regulation of this axis.