Pristimerin Protects Against OVX-Mediated Bone Loss by Attenuating Osteoclast Formation and Activity via Inhibition of RANKL-Mediated Activation of NF-κB and ERK Signaling Pathways

Introduction: Osteoporosis is an osteolytic bone condition characterized by decreased bone strength and increased bone fragility. It is the result of elevated formation or activity of bone-resorbing osteoclasts. Although current therapeutic agents are efficacious against osteoclast-mediated bone loss, detrimental side effects preclude the long-term use of these agents. Pristimerin (PRI) is a naturally occurring quinone-methide triterpenoid that has been revealed to exert anti-inflammatory and anti-tumor effects via regulating various signaling cascades including NF-κB and MAPK activation.

Methods: The bone marrow macrophages were used to confirm the anti-osteoclastic and anti-resorptive functions of PRI in vitro. An in vivo ovariectomy (OVX) model was applied to verify the function of PRI protecting bone loss.

Results: PRI abolished the early activation of NF-κB and ERK MAPK signal cascades thereby thwarting the downstream expression of c-Fos and NFATc1, which prevented the production of mature osteoclasts. In vivo, PRI protects mice against ovariectomy (OVX)-mediated bone loss by diminishing osteoclast formation and bone resorptive activity.

Conclusion: Our study shows that PRI demonstrates therapeutic potential in the effective treatment against osteoclast-induced osteolytic diseases like osteoporosis.