Osteoclast formation and bone resorption induced by tumor necrosis factorª²¦Á

    SUN Siª²Guo, MA Baoª²An, ZHOU Yong, FAN Qingª²Yu

    Department of Orthopaedic Surgery£¬Tangdu Hospital, Fourth Military Medical University£¬Xi¬ðan 710038, China

    ¡¾Abstract¡¿ AIM: To investigate whether tumor necrosis factorª²¦Á (TNFª²¦Á) can induce osteoclast formation from peripheral blood mononuclear cells (PBMCs) independent of receptor activator of nuclear factor kappa B ligand (RANKL). METHODS: PBMCs were cultured in the presence of macrophageª²colony stimulating factor (Mª²CSF) and TNFª²¦Á in vitro. RANKL blocking agent RANK:Fc and neutralizing antiª²TNFª²¦Á antibody were respectively added to the culture. At the end of the culture, PBMCs cultured on coverslips were fixed and stained for tartrate resistant acid phosphatase (TRAP), a marker of osteoclast. Lacuna resorption on dentine slices, a functional marker of osteoclast, was also observed using scanning electron microscopy and light microscopy. RESULTS: TNFª²¦Á induced the formation of multinucleated cells (MNCs) which were TRAP positive and showed evidence of lacuna resorption pit formation on dentine slices. RANK:Fc did not inhibit this process while neutralizing antiª²TNFª²¦Á antibody completely blocked both the formation of MNCs and lacuna resorption. CONCLUSION: In the presence of Mª²CSF, TNFª²¦Á can directly induce mononuclear phagocyte osteoclast precursors to differentiate into osteoclastic cells capable of lacuna resorption. ......