Estrogen promotes apoptosis of murine osteoclasts mediated by TGF-beta.

Postmenopausal osteoporosis, the most common bone disease in the developed world, is associated with estrogen deficiency. This deficiency induces increased generation and activity of osteoclasts, which perforate bone trabeculae, thus reducing their strength and increasing fracture risk. Estrogen replacement prevents these effects, indicating that estrogen negatively regulates osteoclast formation and function, but how it does this is unclear. Because functional osteoclast life span and thus the amount of bone that osteoclasts resorb could also be enhanced following estrogen deficiency, and since sex steroids regulate apoptosis in other target tissues, we investigated whether estrogen may affect osteoclast function by promoting apoptosis. 17 beta-Estradiol promoted apoptosis of murine osteoclasts in vitro and in vivo by two- to threefold. Tamoxifen, which has estrogenic effects on bone resorption, and transforming growth factor-beta 1 (TGF-beta), whose production by osteoblasts is increased by estrogen, had similar effects in vitro. Anti-TGF-beta antibody inhibited TGF-beta-, estrogen- and tamoxifen-induced osteoclast apoptosis, indicating that TGF-beta might mediate this effect. These findings suggest that estrogen may prevent excessive bone loss before and after the menopause by limiting osteoclast life span through promotion of apoptosis. The development of analogues to promote this mechanism specifically could be a useful and novel therapeutic approach to prevent postmenopausal osteoporosis.

Neuromuscular hamartomas of the head and neck.

The neuromuscular hamartoma (also referred to as the neuromuscular choristoma or benign triton tumor) is a rare developmental lesion composed of mature elements of both striated muscle and nerve. To date, less than 20 cases have been reported in the English language literature. The majority of these have involved large nerves, such as the sciatic or brachial plexus, but cutaneous lesions have also been reported. We report 2 cases that involve the head and neck and that are among the few described in this location. The majority of cases have been described in infants and young children. However, 1 of our cases (and at least 1 previously reported case) occurred in an adult. While surgical excision has been the most widely used form of therapy, a few cases have been complicated by and/or associated with a second lesion, such as a fibromatosis or lymphangioma.

Immunolocalization of stress proteins and extracellular matrix proteins in the rat tibia.

Stress proteins (heat shock proteins [hsps]) serve a number of protective functions, including protection from apoptosis and acting as chaperones during protein biosynthesis. For example, hsp 27 has been defined as a chaperone for the G3 domain of aggrecan, while hsp 47 is the chaperone for type I collagen. Separate cytoprotective roles for hsp 27 and hsp 70 have been demonstrated. The aim of this study was to define the expression of hsps in osteoblastic and chondrocytic cells of the growing rat long bone in relationship to the immunohistochemical localization of aggrecan, type I collagen and the presence of fragmented DNA that defines apoptotic events. Tibiae were harvested from Fisher 344 rats (n=6) and fixed in 10% buffered formalin. Samples were decalcified in 10% EDTA, bisected, and processed for histologic examination. Sections (5 mm) were immunohistochemically stained using a streptavidin-biotin detection method. Co-localization of hsps with apoptosis was achieved using the TUNEL procedure. In the rat tibia growth plate, aggrecan was generally distributed throughout cartilage and chondrocytes. However, hsp 27 expression was observed only in the lower hypertrophic chondrocytes. hsp27 was present in osteoblasts lining newly formed bone. hsp 47 staining was also prominent within these osteoblasts where collagen type I immunolocalization occurred. The inducible form of hsp 70 was localized to the osteoblastic cells lining new bone in the primary spongiosa. In cartilage, DNA fragmentation was restricted to the hypertrophic, hsp27-positive, chondrocytes. In contrast, DNA fragmentation was not co-localized with hsp27-positive osteoblastic cells of the primary spongiosa, although occasional apoptotic cells were identified. These results indicate that apoptosis is a mechanism by which hypertrophic chondrocytes are eliminated from cartilage prior to calcification, but that other mechanisms are also likely to be involved. They also suggest that hsps have cytoprotective and biosynthetic functions within osteoblasts and chondrocytes, but apoptotic signals may override these effects in some instances, resulting in apoptosis.

Evaluation of three different dental implants in ligature-induced peri-implantitis in the beagle dog. Part II. Histology and microbiology.

The purpose of this study was to evaluate experimental peri-implant breakdown microbiologically, radiographically and histologically. Hydroxyapatite-coated, titanium plasma-sprayed, and titanium alloy surfaces were investigated. Eighty-four implants were placed in 14 beagle dogs. Standardized radiographs and microbiologic samples (DNA) were obtained. Dogs were sacrificed at 3 and 6 months. Undecalcified histologic sections were prepared. Thickness of hydroxyapatite coating, changes in crestal bone height, and marginal changes in osseointegration were measured. Vertical bone loss was computed. Radiographs were analyzed using computer-assisted densitometric image analysis (CADIA). Microbial analysis (DNA) did not clearly favor any of the examined surfaces. CADIA did not show differences among implant surfaces. No significant differences among the three implants were noted for histometry, except the experimental titanium plasma-sprayed surface showed an increase in vertical bone loss 6 months (P < .05). Thickness of hydroxyapatite was decreased in active peri-implantitis sites (P < .05). Clinical attachment level was shown to be the most sensitive clinical parameter for detecting histologic changes. All implants were equally susceptible to peri-implantitis.

Nerve sheath myxoma of the oral cavity: case report and review.

Nerve sheath myxoma is a benign peripheral nerve sheath tumor that rarely occurs in the oral cavity; approximately 12 cases have been reported to date. On histologic evaluation the lesions consist of closely aggregated fascicles that vary considerably in cellularity. Some of the lesions are predominantly myxoid with widely spaced, stellate-shaped cells. Other lesions consist of closely aggregated spindle cells in a matrix that appears fibrous yet stains strongly for acid mucopolysaccharides (extracellular mucin). Small numbers of mitotic figures may be observed. Because of their rarity and unusual histologic appearance, it is advisable that the pathologist be familiar with these lesions; they may be mistaken for other myxoid lesions of the oral mucosa. We describe a single case of nerve sheath myxoma that arose in the buccal mucosa in a woman.

Pyramidal molar roots and canine-like dental morphologic features in multiple family members: a case report.

We report on three cases of unusual dental morphologic characteristics with pyramidal-shaped premolars and fused molar roots occurring in two generations. The dental abnormalities were hereditary in nature with morphologic features similar to those described by others. The features described in the literature were inherited in a pattern suggestive of a polygenic system with incomplete penetrance, although autosomal dominant inheritance with variable expression was possible. The present cases are found in a fashion suggestive of an autosomal dominant inheritance pattern, but insufficient evidence is available to state this for certain. In this case report, we describe a family with the previously stated anomalies and discuss potential causes for their condition as well as their clinical relevance.

Multiple cutaneous leiomyomas. Report of a case.

Multiple cutaneous leiomyomas usually appear as painful nodules of the skin. Historically these have been treated by surgical excision, however, because they are often numerous, surgery may be an impractical approach. This article reports on a patient with multiple leiomyomas of the face treated by excision as well as a discussion of alternative treatments such as pharmacologic agents that may be used when surgical excision is not feasible.

Markers for macrophage and osteoclast lineages in giant cell lesions of the oral cavity.

PURPOSE: Giant cell lesions of the oral cavity are a well recognized entity. However, the histogenesis of these lesions is still the subject of controversy, with support for both histiocyte/macrophage and osteoclast origins being found in the literature. This study evaluated a set of peripheral giant cell lesions (PGCLs) and central giant cell lesions (CGCLs) for characteristics of both cell types to address this dilemma. MATERIALS AND METHODS: Detection of histiocyte/macrophage characteristics was accomplished immunohistochemically by evaluating for markers specific for this cell type, namely alpha-1 -antichymotrypsin (1 -ACT) and factor XIIIa antibodies. Detection of osteoclast characteristics made use of the fact that osteoclasts possess a unique enzyme, tartrate-resistant acid phosphatase, which can be appreciated by histochemical procedures. RESULTS: A large percentage of the multinucleated cells stained with the 1-ACT (38.08% in PGCLs and 15.84% in CGCLs), while only isolated cells stained for factor XIIIa (1.20% PGCLs, 0.99% CGCLs). Isolated stromal cells also were stained. Virtually all multinucleated cells reacted with the tartrate-resistant acid phosphatase stain (99.26% PGCLs, 98.34% CGCLs), as did a number of the mononuclear stromal cells. CONCLUSIONS: This study supports the contention that GCLs of the oral cavity may arise from precursor cells related to the granulocyte/macrophage line, and may originate from mononuclear cells that express markers for both macrophages and osteoclasts.

Estrogen-induced resistance to osteoblast apoptosis is associated with increased hsp27 expression.

Estrogen has been shown to protect osteoblastic cells from apoptosis. Similarly, estrogen treatment preceding heat shock elevates heat shock protein 27 (hsp27) expression and increases thermoresistance in the murine estrogen receptor-transformed SMER14 osteoblastic cell line. Forced expression of hsp27 expression in other cell lines limits apoptosis. The purpose of this study was to examine the effects of estrogen on staurosporine-induced apoptosis in the context of hsp27 expression. Cell viability was measured by the MTT assay. Early apoptotic events were examined by fluorescent microscopy by using FITC-conjugated Annexin V staining. TUNEL labeling was used to compare the number of apoptotic nuclei following staurosporine treatment of estrogen pretreated or untreated cells. Estrogen treatment increased SMER14 cell viability, but not ROS17/2.8 cell viability, in the presence of staurosporine. Estrogen treatment also reduced annexin V staining and DNA fragmentation. Similar treatment increased SMER14 cell hsp27 levels. The concurrent reduction in induced apoptosis suggests a possible estrogenic mechanism for increasing and/or maintaining the number of viable osteoblasts in bone.

Dental abnormalities associated with failure of tooth eruption in src knockout and op/op mice.

c-src knockout and op/op mice develop osteopetrosis as a result of defective osteoclast function and osteoclast formation, respectively. The mutant mice can be distinguished readily from their wild-type littermates around 10-12 days after birth because their incisors do not erupt, but the morphology of their teeth and surrounding bone has not been reported previously in detail. Histologic examination of jaws of src-mutant mice reveals unerupted, abnormal incisors within their bony crypts. The tooth roots are distorted by foci of haphazard proliferation of odontogenic epithelium associated with primitive tooth structures that strongly resemble the tumor-like lesions in humans, known as odontomas. The crowns of the incisors are fused to the adjacent bone, and the developing periodontal ligament is disordered and hypocellular. Osteoclasts are present in the bone surrounding the distorted teeth, but as in other bones in these mice they lack ruffled borders and thus do not resorb effectively. Similar odontogenic proliferation is present around unerupted incisors in op/op mice which form very few osteoclasts, but the amount is significantly less than in src mutant mice. Molars fail to erupt in both types of mutant mice, but they are not accompanied by aberrant odontogenic proliferation. These findings and previous reports of similar abnormalities in jaws from op/op rats suggest that failure of incisor eruption and associated proliferation of odontogenic epithelium in osteopetrotic rodents are a direct result of defective osteoclastic bone resorption.

Periapical abscess formation and resolution adjacent to dental implants: a clinical report.

The vitality of teeth adjacent to dental implants should be considered in the treatment planning of dental implants. Both the restorability of an endodontically treated tooth and the risk of infection of the adjacent implant are important factors in planning for success. Given the illustrated difficulties and difficulties associated with resolving periapical infections of teeth and implants, it is essential to define the vitality of teeth by careful pulp testing and to consider the integrity of existing questionable, endodontically treated teeth before implant treatment. The risk of periapical infection at teeth adjacent to implants must be minimized.