ABSTRACT
The toothless (tl) osteopetrotic mutation in the rat is characterized by generalized skeletal sclerosis, a severe reduction in the numbers of osteoclasts, monocytes, and macrophages, and absence of tooth eruption. Studies examining gene expression in bone-derived cells of tl rats and their normal littermates have shown that genes related to osteoblast function are aberrantly expressed in tl rats compared to normal littemates. We have previously shown that exogenous administration of colony stimulating factor-1 (CSF-1) to tl rats results in a dramatic reduction of the skeletal sclerosis and significant increases in the number of osteoclasts. Thus, we examined the effects of CSF-1 on osteoblast and osteoclast gene expression in tl rats as demonstrated by Northern blot analysis. While osteoblast-related gene expression as reflected by mRNA levels of alkaline phosphatase, osteocalcin, osteopontin, and type I collagen was normalized, osteoclast-related gene expression, as reflected by mRNA levels of carbonic anhydrase II and tartrate-resistant adenosine triphosphatase, remained significantly lower in CSF-1-treated tl rats compared to untreated normal littermates. Since previous studies have not demonstrated the CSF-1 receptor on osteoblasts, these results suggest that osteoblast abnormalities in tl rats are an effect of the osteopetrotic condition rather than the cause of the disease.
Subject(s)
Gene Expression Regulation/drug effects , Macrophage Colony-Stimulating Factor/pharmacology , Osteoblasts/drug effects , Osteoclasts/drug effects , Osteopetrosis/genetics , Adenosine Diphosphate/metabolism , Alkaline Phosphatase/genetics , Alkaline Phosphatase/metabolism , Animals , Blotting, Northern , Bone and Bones/diagnostic imaging , Bone and Bones/drug effects , Carbonic Anhydrases/genetics , Carbonic Anhydrases/metabolism , Collagen/genetics , Collagen/metabolism , Disease Models, Animal , Gene Expression Regulation/genetics , Histones/genetics , Histones/metabolism , Macrophage Colony-Stimulating Factor/administration & dosage , Macrophage Colony-Stimulating Factor/therapeutic use , Macrophages/cytology , Macrophages/drug effects , Monocytes/cytology , Monocytes/drug effects , Osteoblasts/cytology , Osteocalcin/genetics , Osteocalcin/metabolism , Osteoclasts/cytology , Osteopetrosis/pathology , Osteopetrosis/physiopathology , Osteopontin , RNA, Messenger/metabolism , Radiography , Rats , Receptor, Macrophage Colony-Stimulating Factor/drug effects , Receptor, Macrophage Colony-Stimulating Factor/metabolism , Sialoglycoproteins/genetics , Sialoglycoproteins/metabolism , Tibia/diagnostic imaging , Tibia/drug effectsABSTRACT
Juvenile periodontitis is one of the more debilitating periodontal diseases. The disease entity includes two manifestations of aggressive bone destruction, a localized and a generalized form, which affect adolescents at puberty. Recent studies have defined the prevalence of the disease with regard to locale, gender, and ethnicity. In addition, significant advances have been made in evaluating host response effects in juvenile periodontitis. Studies have identified changes in cell surface receptors on neutrophils, which appear to be related to both receptor density and structure. Various molecular techniques, including restriction fragment length polymorphism, have enabled researchers to identify clonal variants of Actinobacillus actinomycetemcomitans--the microorganism most closely associated with the disease. This may prove to be very useful in identifying virulence factors that have a role in disease initiation and progression. Treatment modalities using debridement, surgery, and anti-infective therapy have been proposed for management of the disease.
