Angela M. Pierce

Osteoclasts: Structure and function

Osteoclasts are multinucleated giant cells showing specialized membrane structures, clear zones and ruffled borders, which are responsible for the process of bone resorption. These cells arrive at the resorption site via the bloodstream as mononuclear cells, derived from haemopoietic precursors in the spleen or bone marrow, which fuse prior to resorption. The osteoclast may share an early progenitor cell, the granulocyte macrophage colony-forming unit (GM-CFU) with monocytes, macrophages and granulocytes, implying that osteoclasts share the pluripotent haemopoietic stem cell with all other haemopoietic cells. In the past, elucidation of the structure of these cells relied upon traditional ultrastructural techniques. Transmission electron microscopic studies revealed details of the unique ultrastructure of these cells and, in combination with stereological techniques, showed the response of cells to various hormonal stimuli. Scanning electron microscopy not only demonstrated the surface appearance of osteoclasts, and their predilection for spreading on various substratum components, but has also been used as an adjunct in resorption assays in which areas of resorption lacunae are measured as indicators of cell activity. Recent advances in fields such as immunocytochemistry and freeze fracture techniques have contributed towards a more detailed delineation of antigenic profile, cytoskeletal structure and localization of enzymatic pathways. The osteoclast is subject to extensive regulatory mechanisms and it has been established that the osteoblast plays a major rôle in mediating the effects of osteotropic hormones and local mediators on these cells. Hence, research aimed at elucidating the coupling mechanisms between these two cells may result in new therapies for bone disease.

Calcitonin as an alternative therapy in the treatment of root resorption.

Inflammatory root resorption is a common finding following trauma and will cause eventual destruction of the tooth root if left untreated. This study examined the effects of intrapulpal application of calcitonin, a hormone known to inhibit osteoclastic bone resorption, on experimental inflammatory root resorption induced in monkeys. Results were histologically evaluated using a morphometric technique and revealed that calcitonin was an effective medicament for the treatment of inflammatory root resorption. It was concluded that this hormone could be a useful therapeutic adjunct in difficult cases of external root resorption.

Lip cancer in south Australia, 1977-1996

Summary Lip cancer (140 ICD‐9, C00 ICD‐10) is a form of oral cancer occurring at the junction between the oral cavity and the skin. Lip cancer has a distinctive global epidemiology that is notably different from cancer occurring at other intraoral sites. This study reviews and analyses the epidemiological data for lip cancer from the South Australian Central Cancer Registry between 1977 and 1996. During this 20‐year period, 2716 cases of lip cancer (2095 male, 621 female) and 35 deaths from this disease (23 males, 12 females) were reported. The average age of diagnosis was 58.3 years in males and 66.0 years in females. Very high age‐standardised incidence rates (over 15.0 per 100 000 per annum in males and 4.0 per 100 000 per annum in females) were found, giving the South Australian population amongst the highest incidence of lip cancer in the world. Also of considerable concern was the finding that, contrary to global trends, these rates showed a significant increase over the 20‐year period in both sexes. Possible reasons for these findings are discussed.

Inherited craniofacial fibrous dysplasia

Craniofacial fibrous dysplasia occurring in a mother and two of her three daughters is reported. In all three patients, the condition was characterized by extensive bilateral and bimaxillary involvement. All patients exhibited radiographic evidence of abnormal maxillary and mandibular bone and tooth displacement. Morphologic examination of deciduous teeth from the daughters showed replacement of normal pulp tissue by fibro-osseous lesion. Because of the familial occurrence of the cases, it is proposed that they comprise an example of inherited craniofacial fibrous dysplasia.

Immunohistochemical detection of nerve growth factor and its receptors in the rat periodontal ligament during tooth movement

OBJECTIVES Nerve growth factor (NGF) and its receptors, p75 and tyrosine receptor kinase A (Trk A), have been shown to increase following trauma. The aims of this study were to examine changes in the detection of NGF and its receptors during orthodontic tooth movement in the rat, and the effects of anti-NGF on these changes. DESIGN Orthodontic separators were placed between the right maxillary first and second molars of Sprague-Dawley rats which were equally divided into two groups. Animals from the second group were injected with anti-NGF. The left sides served as controls, and animals were sacrificed at 0, 3, 7 and 14 days. RESULTS Results of immunohistochemical localisation for p75, Trk A, calcitonin gene-related peptide (CGRP) and NGF showed staining intensity increased at day 3, with a peak at day 7 and decreasing intensity at day 14. Anti-NGF injected animals showed reduced staining at all observation periods. CONCLUSION Data suggest that orthodontic injury induces NGF production, leading to sprouting and invasion by CGRP-positive nerve fibers and that injection of anti-NGF reduces NGF tissue levels and prevents innervation by CGRP-positive fibers.

Identification of basal lamina acidic glycoconjugates, particularly heparan sulphate proteoglycans, using a poly-l-lysine-gold probe in induced oral carcinomas

Acidic glycoconjugates represent the major non-fibrous macromolecular components that form the extracellular and cell-associated matrices of all animal tissues. The constituent molecules are principally structural glycoproteins and proteoglycans. While their protein component is determined by gene pools, it is the polyanionic (acidic) nature of the polysaccharides, determined by their degrees of carboxylation and sulphation, which confers both functional and diagnostic status on these molecules. Sulphated glycoconjugates in the basal laminae have been reported to play a role in tumour invasion and metastasis. In this study, we used cationic colloidal gold together with transmission electron microscopic methods to compare the expression of acidic glyconconjugates in the basal lamina of both normal rat tongue mucosa and experimentally induced oral carcinomas. Results indicated that heparan sulphate rich glycoconjugates were predominant and were mostly confined to the lamina lucida of the basal lamina in normal oral mucosa. Conversely, observation of basal laminae associated with induced carcinomas showed less intense and more widely dispersed gold labelling for heparan sulphate. The observed differences in gold labelling may reflect modified metabolism of sulphated glycoconjugates or result from the action of degradative enzymes in the induced tumours.