Normal development of dental innervation and nerve/tissue interactions in the colony-stimulating factor-1 deficient...

Dental innervation occurs concurrently with tooth development, eruption, and root formation and is suggested to interact with developing tissues. The purpose of the present study was to investigate dental innervation in osteopetrotic (op/op) mice, which carry a mutation of colony-stimulating factor-1 (CSF-1) and demonstrate sparse macrophages and osteoclasts, failure of bone resorption, lack of tooth eruption, and poor root formation. Jaw tissues from 21 mice in different age groups (7 days, 18 days, 26 days, 5 weeks, and 3 months) were prepared for immunocytochemistry and light microscopy. Immunocytochemistry with the neuronal marker protein gene product 9.5 (PGP 9.5), macrophage marker F4/80, double-labeling with F4/80 and PGP 9.5, and histochemical analysis using tartarate-resistant acid phosphatase (TRAPase) were carried out in selected sections. Molar and incisor development were arrested in the op/op mouse, and both types of teeth had bony occlusion of the eruptive pathway and failure of root formation. Third molar development in the normal mouse is delayed until after birth; therefore, it encounters different bone barriers and jaw structures than are present when first and second molars and incisors begin to develop after the second embryonic week. All three molars, however, completed crown formation prior to eruption failure. Partial root formation was seen in several homozygous op/op mice, and, in those cases, there was partial development of the periodontal ligament. Innervation of dental tissues that successfully formed was essentially normal in the mutant mice despite phenotypic deficiencies in macrophages and osteoclasts. The periodontal ligament was innervated with PGP 9.5-immunoreactive Ruffini mechanoreceptive endings in those cases in which the ligament formed, and op/op mice had remarkably normal sensory innervation of molar and incisor pulp despite failure of bone resorption, failure of root development, and arrested eruption. This study shows that op/op mice develop normal innervation in dental tissues and that dental nerve development proceeds independently of bone abnormalities and root failure in this animal.