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

Inflammatory cytokines such as interleukin-1 alpha (IL-1 alpha) are increased in teeth with periapical lesions. Primary teeth with periapical lesions have a propensity for accelerated eruption of the successors. In this study, we asked whether increased levels of IL-1 alpha 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-1 alpha on osteogenic differentiation, osteoclastogenic activity, and matrix remodeling of DFCs. Results demonstrated that DFCs cultured with IL-1 alpha exhibited reduced osteogenic capacity, higher osteoclastogenic activity, and stronger invasive ability. Phosphorylation of JNK and p38 was upregulated, and pretreatment with SB203580 and SP600125 reversed the effect of IL-1 alpha on DFCs. Neonatal rats subjected to subcutaneous injection of an IL-1 receptor antagonist exhibited a reduced number in activated osteoclasts, increased expression of alkaline phosphatase and osteopontin, and delayed tooth eruption. These data support our hypothesis that increased IL-1 alpha cytokine levels as they occur during periodontal and periapical 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.