Augmentative Effect of IgG on RANKL-mediated Osteoclastogenesis

A positive correlation between disease occurence and elevated serum IgG response to certain bacteria implies that IgG response can be associated with the development of bone resorption in periodontal disease. It has been recently demonstrated that costimulatory signals elicited by the common Fc receptor gamma chain (FcRγ) and/or other membrane adaptor molecules can augment the receptor activator of NF-kB ligand (RANKL)-mediated osteoclastogenesis. Objective: We hypothesize that immune complex formation of IgG-antibody with bacterial antigens may affect RANKL-mediated osteoclastogenesis. Methods: Exp-1) Fc receptor expression on RAW264.7 osteoclast precursor cells was examined by flow cytometry. RAW264.7 cells were cultured in 96-well plates with immobilized mouse IgG in the presence or absence of RANKL for 5 days. Exp-2) BALB/c bone marrow cells were stimulated with RANKL plus M-CSF in the presence or absence of Actinobacillus actinomycetemcomitans Omp29-IgG-antibody immune complex (Omp29-IC), Omp29, or soluble IgG-antibody for 9 days. Exp-3) Omp29-IC, RANKL or saline was injected into BALB/c mouse calvaria. The calvaria removed at Day10 and cell cultures were stained for TRAP activity. TRAP+ multinucleated cells were counted as mature osteoclast cells. Results: Exp-1) Flow cytometry demonstrated that RAW264.7 cells express FcRII and FcRIII constitutively. Stimulation of RAW264.7 cells with immobilized IgG, but not soluble IgG, enhanced RANKL-mediated osteoclastogenesis, whereas immobilized IgG alone did not affect the RANKL-mediated osteoclastogenesis. Exp-2) RANKL- and M-CSF-induced osteoclastogenesis by bone marrow cells was enhanced in the presence of Omp29-IC, but not Omp29 alone. Exp-3) Injection of Omp29-IC as well as RANKL into BALB/c mouse calvaria induced a remarkable number of TRAP+ multinucleated cells in the calvarial bone marrow cavities compared to the saline control. Conclusion: The immobilized IgG and IgG-immune complex augmented RANKL-mediated osteoclastogenesis. These findings may delineate a novel role for IgG in the development of bone resorption in periodontal disease.

Support NIDCR grants DE-03420, DE-14551, DE-15722.