The mononuclear phagocyte system revisited

The mononuclear phagocyte system (MPS) was defined as a family of cells comprising bone marrow progenitors, blood monocytes, and tissue macrophages. In this review, we briefly consider markers for cells of this lineage in the mouse, especially the F4/80 surface antigen and the receptor for macrophage colony-stimulating factor. The concept of the MPS is challenged by evidence that there is a separate embryonic phagocyte lineage, the blurring of the boundaries between macrophages and other cells types arising from phenotypic plasticity and transdifferentiation, and evidence of local renewal of tissue macrophage populations as opposed to monocyte recruitment. Nevertheless, there is a unity to cells of the MPS suggested by their location, morphology, and shared markers. We discuss the origins of macrophage heterogeneity and argue that macrophages and antigen-representing dendritic cells are closely related and part of the MPS.

Oral ulceration with bone sequestration

Oral mucosal ulceration is a common manifestation of various disease processes. Identification of the aetiological factor(s) involved greatly facilitates the management of such conditions. This report describes oral ulceration of the mucosa overlying the lingual shelf and mylohyoid ridge of the mandible and, less commonly on tori and exostoses, in association with bone sequestration. Trauma, which involves the subjacent periosteum resulting in a focus of ischaemic bone necrosis, in conjunction with local anatomical and perhaps other systemic predisposing factors, forms the aetiopathogenesis for this particular type of focal ulcerative lesion.

Growth hormone regulates osteogenic marker mRNA expression in human periodontal fibroblasts and alveolar bone-derived cells

Background: Growth hormone (GH) is a potent regulator of bone formation. The proposed mechanism of GH action is through the stimulation of osteogenic precursor Cell proliferation and, following clonal expansion of these cells. promotion of differentiation along the osteogenic lineage. Objectives: We tested this hypothesis by studying the effects of GH on primary cell populations of human periodontal ligament cells (PLC) and alveolar bone cells (ABC), which contain a spectrum of osteogenic precursors. Method: The cell populations were assessed for mineralization potential after long-term culture in media containing beta-glycerophosphate and ascorbic acid, by the demonstration of mineral deposition by Von Kossa staining. The proliferative response of the cells to GH was determined over a 48-h period using a crystal violet dye-binding assay. The profile of the cells in terms of osteogcnic marker expression was established using quantitative reverse transcriptase polymerase chain reaction (RT-PCR) for alkaline phosphatase (ALP), osteopontin. osteocalcin, bone sialoprotein (BSP), as well as the bone morphogenetic proteins BMP-2, BMP-4 and BMP-7. Results: As expected, a variety of responses were observed ranging from no mineralization in the PLC populations to dense mineralized deposition observed in one GH-treated ABC population. Over a 48-h period GH was found to be non-mitogenic for all cell populations. Quantitative reverse transcriptase polymerase chain reaction (RT-PCR) BSP mRNA expression correlated well with mineralizing potential of the cells. The change in the mRNA expression of the osteogenic markers was determined following GH treatment of the cells over a 48-h period. GH caused an increase in ALP in most cell populations, and also in BMP expression in some cell populations. However a decrease in BSP. osteocalcin and osteopontin expression in the more highly differentiated cell populations was observed in response to GH. Conclusion: The response of the cells indicates that while long-term treatment with GH may promote mineralization, short-term treatment does not promote proliferation of osteoblast precursors nor induce expression of late osteogenic markers.

Morphology, ultrastructure, and implied function of ciliated sensory structures on the developmental stages of Merizocotyle icopae (Monogenea : Monocotylidae)

Experimental infections were used to track the fate of the dorsal sensilla of Merizocotyle icopae (Monogenea: Monocotylidae) from nasal tissue of the shovelnose ray, Rhinobatos typus (Rhinobatidae). Scanning and transmission electron microscopy revealed that 3 types of uniciliate dorsal sensilla exist at different times in the development of the monogenean. Type 1 sensilla have little or no invagination where the cilium exits the distal end of the dendrite and possess a ring of epidermis surrounding the cilium distal to the invagination. Type 2 sensilla have a deep invagination where the cilium exits the dendrite. Type 3 sensilla can be distinguished from the other types by the shape of the dendrite. The larvae have predominantly Type I dorsal sensilla, most of which are lost approximately 24 h after infection and a few Type 2 sensilla, which are retained. Additional Type 2 sensilla (termed Adult Type 2 sensilla), which are slightly different morphologically from the Type 2 sensilla of the larvae, form in later stages of development. Numerous Type 3 sensilla are unique to the dorsal surface of adults. Loss of all Type I sensilla upon attachment to the host, R. typus, suggests that these may be chemo- or mechanoreceptors responsible for host location by the swimming infective larvae. Type 2 sensilla appear to be important in the larvae, juveniles, and adults whereas the modality mediated by Type 3 is specific to adults. (C) 2003 Wiley-Liss, Inc.

Tissue engineering for bone regeneration using differentiated alveolar bone cells in collagen scaffolds

Regeneration of osseous defects by a tissue-engineering approach provides a novel means of treatment utilizing cell biology, materials science, and molecular biology. In this study the concept of tissue engineering was tested with collagen type I matrices seeded with cells with osteogenic potential and implanted into sites where osseous damage had occurred. Explant cultures of cells from human alveolar bone and gingiva were established. When seeded into a three-dimensional type I collagen-based scaffold, the bone-derived cells maintained their osteoblastic phenotype as monitored by mRNA and protein levels of the bone-related proteins including bone sialoprotein, osteocalcin, osteopontin, bone morphogenetic proteins 2 and 4, and alkaline phosphatase. These in vitro-developed matrices were implanted into critical-size bone defects in skulls of immunodeficient (SCID) mice. Wound healing was monitored for up to 4 weeks. When measured by microdensitometry the bone density within defects filled with osteoblast-derived matrix was significantly higher compared with defects filled with either collagen scaffold alone or collagen scaffold impregnated with gingival fibroblasts. New bone formation was found at all the sites treated with the osteoblast-derived matrix at 28 days, whereas no obvious new bone formation was identified at the same time point in the control groups. In situ hybridization for the human-specific Alu gene sequence indicated that the newly formed bone tissue resulted from both transplanted human osteoblasts and endogenous mesenchymal stem cells. The results indicate that cells derived from human alveolar bone can be incorporated into bioengineered scaffolds and synthesize a matrix, which on implantation can induce new bone formation.

Ultrastructure of developing tooth plates in the Australian lungfish, Neoceratodus forsteri (Osteichthyes : Dipnoi)

While the lungfish dentition is partially understood as far as morphology and light microscopic structure is concerned, the ultrastructure is not. Each tooth plate is associated with a dental lamina that develops from the inner layer of endodermal cells that form the oral epithelium. Dentines, bone and cartilage of the jaws differentiate from mesenchyme cells aggregating beneath the oral endothelium. Enamel, in the developing and in the mature form, has similarities to that of other early vertebrates, but unusual characters appear as development proceeds. Ameloblasts are capable of secreting enamel, and, with mononuclear osteoclasts, of remodelling the bone below the tooth plate. The forms of dentine, all based largely on an extracellular matrix of collagen and mineralised with biological apatite, differ from each other and from the underlying bone in the ultrastructure of associated cells and in the mineralised extracellular matrices produced. Cell processes emerging from the odontoblasts and from the osteoblasts vary in length, degree of branching and of anastomoses between the processes, although all of the cell types have large amounts of rough endoplasmic reticulum. Mineralisation of the extracellular matrices varies among the enamel, dentines and bone in the tooth plate. In addition, the development of the hard tissues of the tooth plates indicates that many of the similarities in fine structure of the dentition in lungfish, to tissues in other fish and amphibia, apparent early in development, disappear as the dentition matures. (C) 2003 Elsevier Ltd. All rights reserved.

Developmental anomalies in the tooth plates and jaw bones of lungfish

Lungfish of the tooth-plated lineage, both fossil and living, may be affected by alterations in the permanent tooth plates and associated jaw bones as they grow. In a few taxa, the unusual structures may be so common that they must be considered as normal for those species, or as a variation of the normal condition. In others the condition is rare, affecting only a few individuals. Variations, or anomalies, may appear in the growing tissues of the lungfish tooth plate at any time in the life cycle, although they usually appear early in development. Once the changes appear, they persist in the dentition. The altered structures include divided or intercalated ridges, short ridge anomaly, changes in the shape, number and position of cusps, pattern loss, and fused ridges or cusps. Criteria used to distinguish alteration from normal conditions are the incidence of the character in the population, the associated changes in the jaw bone, and the position of the altered structure in the tooth plate. The occurrence of similar changes across a wide range of different species suggests that they may have a genetic cause, especially when they are a rare occurrence in most taxa, but common enough to be a part of the normal variation in others. Prevalence of related anomalies throughout the history of the group suggests that dipnoans of the tooth-plated lineage are closely related, despite significant differences in morphology, microstructure, and function of the denfitions.

In ovo electroporation of Crim1 in the developing chick spinal cord

The novel mammalian gene Crim1 encodes a transmembrane bound protein with similarity to the secreted bone morphogenetic protein (BMP) antagonists, vertebrate Chordin, and its Drosophila homologue short gastrulation. Crim1 is expressed in the neural tube in mouse in a restricted pattern, but its function in central nervous system development is largely unknown. We isolated the chicken Crim1 orthologue and analyzed its expression in the developing neural tube. Chicken CRIM1 shares strong homology to human/mouse CRIM1 and C. elegans CRIM1-like proteins. Crim1 is expressed in a similar but not identical pattern to that in the developing spinal cord of mouse, including the notochord, floor plate, motor neurons, and the roof plate. Unlike follistatin, a secreted inhibitor of BMPs, in ovo electroporation of CRIM1, as a full-length transmembrane bound or secreted ectodomain was not sufficient to disrupt early patterning of the neural tube. However, ectodomain CRIM1 overexpression leads to an approximate 50% decrease in populations of specific ventral neuronal populations, including ISL-1(+) motor neurons, CHX-10(+) V1, and EN-1(+) V2 interneurons.

CRIM1 Regulates the Rate of Processing and Delivery of Bone Morphogenetic Proteins to the Cell Surface

The Crim1 gene is predicted to encode a transmembrane protein containing six von Willebrand-like cysteine-rich repeats (CRRs) similar to those in the BMP-binding antagonist Chordin (Chrd). In this study, we verify that CRIM1 is a glycosylated, Type I transmembrane protein and demonstrate that the extracellular CRR-containing domain can also be secreted, presumably via processing at the membrane. We have previously demonstrated Crim1 expression at sites consistent with an interaction with bone morphogenetic proteins (BMPs). Here we show that CRIM1 can interact with both BMP4 and BMP7 via the CRR-containing portion of the protein and in so doing acts as an antagonist in three ways. CRIM1 binding of BMP4 and -7 occurs when these proteins are co-expressed within the Golgi compartment of the cell and leads to (i) a reduction in the production and processing of preprotein to mature BMP, (ii) tethering of pre-BMP to the cell surface, and (iii) an effective reduction in the secretion of mature BMP. Functional antagonism was verified by examining the effect of coexpression of CRIM1 and BMP4 on metanephric explant culture. The presence of CRIM1 reduced the effective BMP4 concentration of the media, thereby acting as a BMP4 antagonist. Hence, CRIM1 modulates BMP activity by affecting its processing and delivery to the cell surface

A longitudinal analysis of sex differences in bone mineral accrual in healthy 8-19-year-old boys and girls

Background: Although early in life there is little discernible difference in bone mass between boys and girls, at puberty sex differences are observed. It is uncertain if these differences represent differences in bone mass or just differences in anthropometric dimensions. Aim: The study aimed to identify whether sex independently affects bone mineral content (BMC) accrual in growing boys and girls. Three sites are investigated: total body (TB), femoral neck (FN) and lumbar spine (LS). Subjects and methods: 85 boys and 67 girls were assessed annually for seven consecutive years. BMC was assessed by dual energy X-ray absorptiometry (DXA). Biological age was defined as years from age at peak height velocity (PHV). Data were analysed using a hierarchical (random effects) modelling approach. Results: When biological age, body size and body composition were controlled, boys had statistically significantly higher TB and FN BMC at all maturity levels (p < 0.05). No independent sex differences were found at the LS (p > 0.05). Conclusion: Although a statistical significant sex effect is observed, it is less than the error of the measurement, and thus sex difference are debatable. In general, sex difference are explained by anthropometric difference

Physical Activity and Bone Mineral Accrual During Childhood and Adolescence

The epidemic that is osteoporosis has led to an increasing interest in bone mineral, and the factors that influence the levels of bone mineral, in recent years. While it is unrealistic to try and turn back the clock, a return to an increased level of physical activity may be an important consideration in terms of skeletal health. Peak bone mass is largely determined by heredity, but lifestyle and dietary patterns also influence the level of bone mineral accrued during the growing years. In this review, we summarize the evidence that vigorous weight-bearing physical activity and adequate calcium intake represent the best possibility for enhancing the attainment of an optimal level of bone mineral, within genetic limits.

Abnormalities of the PTH-vitamin D axis and bone turnover markers in children, adolescents and adults with cystic fibrosis: comparison with healthy controls

Abnormalities of calcium and vitamin D metabolism in cystic fibrosis (CF) are well documented. We tested the hypothesis that alterations in calcium metabolism are related to vitamin D deficiency, and that bone resorption is increased relative to accretion in patients with CF. Calcitropic hormones, electrolytes, osteocalcin (OC) and bone alkaline phosphatase (BAP), (markers of bone mineralisation), urinary deoxypyridinoline [total (t) Dpd, a marker of bone resorption] and lumbar spine bone mineral density (LS BMD), expressed as a z-score, were measured in 149 (81 M) CF and 141 (61 M) control children aged 5.3-10.99 years, adolescents aged 11-17.99 years and adults aged 18-55.9 years. Data were analysed by multiple regression to adjust for age. In patients, FEV1% predicted and CRP (as disease severity markers), genotype and pancreatic status (PS) were recorded. The distribution of PTH differed between groups (P

Gender differences in CF phenotype associated with low bone mineral density

Adolescents and adults with CF have lower bone mineral density (BMD) than normal, but its relationship with phenotype is not well understood. Point FEV1% predicted (FEV) and rate of change of FEV are biased estimates of disease severity, because progressively older subjects represent a selected survivor population, with females at greater risk of death than males. To investigate the relationship between BMD and phenotype we used an index (predicted age at death) derived from Bayesian estimates of slope and intercept of FEV, age at last measurement and survival status. Predictive equations for the index were derived from 97 subjects (78 survivors) from the RCH CF clinic, and applied to a group of 102 comparable subjects who had BMD measured, classified as having‘mild’ ()75th), ‘moderate’ (25– 75th), or ‘severe’ (-25th centile) phenotype. Total body (TB) and lumbar spine (LS) BMD z-scores (Z) were compared, adjustingfor gender effects, using 2-way ANOVA. Annual mean change in FEV segregated, as expected, according to phenotype, ‘severe’ (ns25), ‘moderate’ (ns51) and ‘mild’ (ns25) y3.01(y3.73 to y2.30)%, y0.85(y1.36 to y0.35)%, 2.70(1.92 to 3.46)%, respectively, with no gender difference. LS and TB BMDZ were different in each phenotype (P-s 0.002), LS BMDZ for ‘severe’, ‘moderate’ and ‘mild’ y1.63(CI: y2.07 to y 1.19), y0.86(CI: y1.17 to y0.55), y0.06(CI: y0.54 to 0.41). Males had lower LS BMDZ than females overall (y1.22 (CI: y1.54 to y0.91) vs. y0.48(CI: y 0.84 to y0.12) Ps0.002). In the ‘severe’ group, males had lower TB BMDZ and LS BMDZ (PF0.002). Low BMD is associated with ‘moderate’ and ‘severe’ phenotypes, with relative preservation in females in the ‘severe’ group. Female biology (reproductive fitness) might promote resistance to bone resorption at a critical level of BMD loss.

Sex- and race-related differences in cross-sectional geometry and bone density of the femoral mid-shaft in older adults

Background : Femoral shaft fracture incidence increases in older adults and is associated with low-energy trauma. Apart from bone density, the distribution and size of bone contributes to its strength. Aim : To examine if bone geometry and density of the femoral mid-shaft in older adults differs by sex and race, we studied 197 White women, 225 Black women, 242 White men, and 148 Black men aged 70-79 years participating in the Health, Aging, and Body Composition study; a prospective cohort study in the USA. A secondary purpose of the study was to examine the association of site-specific muscle and fat to bone geometry and density. Subjects and methods : Subjects were community-dwelling and reported no difficulty walking one-quarter of a mile or climbing stairs. Mid-femoral volumetric bone mineral density (vBMD, mg cm -3 ), total area (TA), cortical area (CA), medullary area (MA), cross-sectional moments of inertia (CSMI: I x , I y , J ), and muscle and fat areas (cm 2 ) were determined by computed tomography (CT; GE CT-9800, 10 mm slice thickness). Results : vBMD was greater in men than women with no difference by race ( p < 0.001). Bone areas and area moments of inertia were also greater in men than women ( p < 0.001), with Black women having higher values than White women for TA and CA. Standardizing geometric parameters for body size differences by dividing by powers of femur length did not negate the sex difference for TA and MA. Significant differences ( p < 0.05) among the four groups also remained for I x and J . Mid-thigh muscle area was an independent contributor to TA in all groups (Std beta = 0.181-0.351, p < 0.05) as well as CA in women (Std beta = 0.246-0.254, p < 0.01) and CSMI in White women (Std beta = 0.175-0.185, p < 0.05). Further, muscle area was a significant contributor to vBMD in Black women. Conclusion : These results indicate that bone geometry and density of the femoral diaphysis differs primarily by sex, rather than race, in older well-functioning adults. In addition, site-specific muscle area appears to have a potential contributory role to bone geometry parameters, especially in women.