IL-1α regulates osteogenesis and osteoclastic activity of dental follicle cells via JNK and p38 MAPK pathways.

Inflammatory cytokines such as interleukin-1α (IL-1α) are increased in teeth with periapical lesions. Primary teeth with periapical lesions have a propensity for accelerated eruption of the successors. In the present study, we asked whether increased levels of IL-1α in the dental follicle (DF) occurring as the result of periapical lesions promote tooth eruption, possibly due to enhanced osteoclastic remodeling of DF cells (DFCs). To this end, we studied the effect and possible mechanism of IL-1α on osteogenic differentiation, osteoclastogenic activity and matrix remodeling of DFCs. Results demonstrated that DFCs cultured with IL-1α exhibited reduced osteogenic capacity, higher osteoclastogenic activity, and stronger invasive ability. Phosphorylation of JNK and p38 were up-regulated, and pretreatment with SB203580 and SP600125 reversed the effect of IL-1α on DFCs. Neonatal rats subjected to subcutaneous injection of an IL-1 receptor antagonist exhibited a reduced number in activated osteoclasts, increased expression of ALP and OPN, and delayed tooth eruption. These data support our hypothesis that increased IL-1α cytokine levels as they occur during periodontal and peri-apical inflammation cause osteoclastic remodeling of the alveolar socket as a requirement for tooth eruption and thus may indirectly promote the vertical eruption of teeth toward the occlusal plane.