Wear particles that detach from the surface of
prostheses induce excessive activation of osteoclast and immoderate release of inflammatory
cytokines that lead to peri-implant
osteolysis and aseptic loosening. In this work, we investigated whether
magnoflorine, a quaternary
aporphine alkaloid extracted from the Chinese herb Magnolia or Aristolochia, could effectively inhibit inflammatory calvarial
osteolysis caused by
titanium particles in mouse models, inflammatory response as well as osteoclastogenesis in vitro mediated via receptor activator of NF-κB
ligand (RANKL). Micro-computed tomography and histological examination of mice treated with
magnoflorine revealed fewer resorption pits, less osteoclasts formation and inflammatory
cytokine expression. Moreover, in vitro differentiation of osteoclasts and
bone resorption as well as
titanium particle-induced inflammatory response were dose-dependently inhibited by
magnoflorine. These were accompanied by reduced transcription of osteoclast-specific genes encoding
tartrate-resistant acid phosphatase (TRAP), V-
ATPase d2, c-Fos,
cathepsin K, nuclear factor of activated T cells (NFAT) c1, and
calcitonin receptor (CTR). Further research on mechanism showed that the inhibition of phosphorylation of TAK1 and subsequent activation of MAPK and NF-κB signaling pathways were found to mediate the suppressive effects of
magnoflorine. Collectively, these results suggested that
magnoflorine treatment could effectively prevent peri-implant
osteolysis due to wear debris as well as other diseases caused by chronic
inflammation and excessive osteoclast activation.