This research proposal is an investigation of the local control of alveolar bone metabolism using the precisely timed and localized events of premolar tooth eruption in the dog. In this model system eruption of mandibular premolars is dependent upon the presence of the dental follicle, is independent of the tooth or its development and is characterized by a coordinated resorption of alveolar bone above and formation of bone below the space occupied by the tooth. Recent work from our laboratories has shown that the follicle is adjacent to these polarized areas of alveolar bone formation and resorption, that these respective activities depend upon the follicle and that its coronal aspect next to the resorption area is infiltrated by mononuclear cells just prior to eruption. These cells are monocytes by ultrastructural and cytochemical criteria and have characteristics of pre-osteoclasts. Biochemical studies show that the collagen and proteoglycan content of the follicle change during eruption and that characteristic sialoproteins herald eruption. One of 95k exhibits properties of a structural protein and reduces in amount with eruption. Three of 20-25k appear when eruption begins. Our hypothesis is that these events are related to eruption and that completion of enamel (crown) formation signals eruption through changes in the enamel organ. This proposal explores this hypothesis by examining the role of the enamel organ and collagen in early and late prefunctional eruption and biochemical changes in the enamel organ, basal and coronal areas of the follicle and characteristic follicle proteins during eruption. These studies will employ microsurgical, morphological, biochemical and molecular biological methods to define chemical and molecular events in tooth eruption. Future studies will examine strategies for surgical and molecular interceptions of tooth eruption and alveolar bone metabolism in this in vivo model. The proposed research has significance not only for better clinical management of ectopic and retarded eruption but also for better management of alveolar bone metabolism in development and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE005996-09
Application #
2129279
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1981-09-01
Project End
1994-12-31
Budget Start
1993-07-01
Budget End
1994-12-31
Support Year
9
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Massachusetts Medical School Worcester
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
660735098
City
Worcester
State
MA
Country
United States
Zip Code
01655
Volejnikova, S; Laskari, M; Marks Jr, S C et al. (1997) Monocyte recruitment and expression of monocyte chemoattractant protein-1 are developmentally regulated in remodeling bone in the mouse. Am J Pathol 150:1711-21
Marks Jr, S C; Schroeder, H E (1996) Tooth eruption: theories and facts. Anat Rec 245:374-93
Sweet, H O; Marks Jr, S C; MacKay, C A et al. (1996) Dense incisors (din): a new mouse mutation on chromosome 16 affecting tooth eruption and body size. J Hered 87:162-7
Marks Jr, S C; Cielinski, M J; Sundquist, K T (1996) Bone surface morphology reflects local skeletal metabolism. Microsc Res Tech 33:121-7
Marks Jr, S C (1995) The basic and applied biology of tooth eruption. Connect Tissue Res 32:149-57
Cielinski, M J; Jolie, M; Wise, G E et al. (1995) The contrasting effects of colony-stimulating factor-1 and epidermal growth factor on tooth eruption in the rat. Connect Tissue Res 32:165-9
Popoff, S N; Marks Jr, S C (1995) The heterogeneity of the osteopetroses reflects the diversity of cellular influences during skeletal development. Bone 17:437-45
Marks Jr, S C; Sundquist, K T (1995) Bafilomycin A1 in bone resorption and tooth eruption in dogs. Eur J Oral Sci 103:231-5
Marks Jr, S C; Larson, E K; Wise, G E et al. (1995) Collagen metabolism and tooth eruption: the effects of sodium morrhuate infusions on premolar eruption in dogs. Schweiz Monatsschr Zahnmed 105:1029-32
Sundquist, K; Larson, E K; Marks Jr, S C (1995) Altering tooth eruption by blocking bone resorption--the local delivery of bafilomycin A1. Connect Tissue Res 32:159-63

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