The growth and osteoclastogenic effects of fibroblasts isolated from keratocystic odontogenic tumor

Oral Diseases (2012) Objectives: To investigate the growth characteristics and effects on osteoclastogenesis in fibroblasts isolated from keratocystic odontogenic tumor (KCOT) fibrous capsule. Materials and Methods: Fibroblasts isolated from KCOT fibrous capsule and normal gingival mucosa were cultured in vitro. Their colony‐forming units and proliferative activity were investigated, and the osteoclastogenic effects were also observed by a co‐culture system with osteoclast precursor cell line Raw264.7. The mRNA of several genes related to bone resorption (IL‐6, VEGF, COX‐2, and M‐CSF) was analyzed by real‐time PCR. Results: Keratocystic odontogenic tumor fibroblasts developed fewer CFU and had longer population doubling time than gingival fibroblasts (P < 0.05). In contrast to gingival fibroblasts, KCOT fibroblasts expressed less IL‐6, COX‐2, and M‐CSF (P < 0.05); however, the Raw264.7 co‐cultured with KCOT fibroblasts developed more osteoclast‐like cells and expressed higher level of nfatc1 than that co‐cultured with gingival fibroblasts. Increased COX‐2 expression and VEGF expression were detected in KCOT fibroblasts and Raw264.7 co‐culture system (P < 0.05). Conclusion: Although KCOT fibroblasts showed lower level of cell proliferation than gingival fibroblasts, higher osteoclastogenic ability was detected when co‐cultured with Raw264.7. These results suggest that the cell–cell interaction in the co‐culture system, possibly by increasing COX‐2 and VEGF expression, may be responsible for the increased osteoclastogenic effects of KCOT fibroblasts.