Fractures, particularly at the lower extremities and hip, are a complication of diabetes. In both type 1 (T1D) and type 2 diabetes (T2D), fracture risk is disproportionately worse than that predicted ...from the measurement of bone mineral density. Although an explanation for this discrepancy is the presence of organic matrix abnormalities, it has not been fully elucidated how advanced glycation endproducts (AGEs) relate to bone deterioration at both the macroscopic and microscopic levels. We hypothesized that there would be a relationship between skeletal AGE levels (determined by Raman microspectroscopy at specific anatomical locations) and bone macroscopic and microscopic properties, as demonstrated by the biomechanical measures of crack growth and microindentation respectively. We found that in OVE26 mice, a transgenic model of severe early onset T1D, AGEs were increased by Raman (carboxymethyl-lysine CML wildtype (WT): 0.0143 ±0.0005 vs T1D: 0.0175 ±0.0002, p = 0.003) at the periosteal surface. These differences were associated with less tough bone in T1D by fracture mechanics (propagation toughness WT: 4.73 ± 0.32 vs T1D: 3.39 ± 0.24 NM/m1/2, p = 0.010) and by reference point indentation (indentation distance increase WT: 6.85 ± 0.44 vs T1D: 9.04 ± 0.77 μm; p = 0.043). Within T1D, higher AGEs by Raman correlated inversely with macroscopic bone toughness. These data add to the existing body of knowledge regarding AGEs and the relationship between skeletal AGEs with biomechanical indices.
Breaking the Gingival Barrier in Periodontitis Vitkov, Ljubomir; Singh, Jeeshan; Schauer, Christine ...
International journal of molecular sciences,
02/2023, Volume:
24, Issue:
5
Journal Article
Peer reviewed
Open access
The break of the epithelial barrier of gingiva has been a subject of minor interest, albeit playing a key role in periodontal pathology, transitory bacteraemia, and subsequent systemic low-grade ...inflammation (LGI). The significance of mechanically induced bacterial translocation in gingiva (e.g., via mastication and teeth brushing) has been disregarded despite the accumulated knowledge of mechanical force effects on tight junctions (TJs) and subsequent pathology in other epithelial tissues. Transitory bacteraemia is observed as a rule in gingival inflammation, but is rarely observed in clinically healthy gingiva. This implies that TJs of inflamed gingiva deteriorate, e.g., via a surplus of lipopolysaccharide (LPS), bacterial proteases, toxins, Oncostatin M (OSM), and neutrophil proteases. The inflammation-deteriorated gingival TJs rupture when exposed to physiological mechanical forces. This rupture is characterised by bacteraemia during and briefly after mastication and teeth brushing, i.e., it appears to be a dynamic process of short duration, endowed with quick repair mechanisms. In this review, we consider the bacterial, immune, and mechanical factors responsible for the increased permeability and break of the epithelial barrier of inflamed gingiva and the subsequent translocation of both viable bacteria and bacterial LPS during physiological mechanical forces, such as mastication and teeth brushing.
Abstract Important aspects of bone tissue quality include the physicochemical properties of its main constituents, the organic matrix and the mineral crystals. One of the most commonly reported ...measurements of Raman analysis of bone is the mineral to matrix ratio, obtained from the ratio of the integrated areas of any of the phosphate and amide peaks which depend on both tissue organization and composition. Cube-like samples of normal mouse cortical bone taken from the diaphysis and metaphysis of the femur were investigated within different age groups (2, 4, 8 and 12 weeks) by Raman microspectroscopy. Anatomically identical bone in both longitudinal and transverse directions was analyzed, enabling the discrimination between orientation and composition changes both as a function of animal age, and tissue age within the same animal. The results of the present study indicate that there is a parallel evolution of both orientation and chemical composition as a function of animal age, as well as tissue age within the same specimen. Our tissue age modified ratio of the carbonate to phosphate Raman peaks suggests that the bone mineral crystallite maturity remains relatively constant with animal age. Comparisons of polarized and depolarized experiments in the transversal plane of the diaphysis show a lack of orientation effects as a function of tissue age within the same animal, but exhibit differences as a function of animal age. In the metaphysis, the orientation effect is evident too, albeit less pronounced. This is most likely due to either the age difference between the two tissues within the same specimen in the long bone axis, as metaphyseal bone is generally younger than diaphyseal, or the more random orientation of the tissue collagen itself.
Abstract
Context:
Recessive mutations in TMEM38B cause type XIV osteogenesis imperfecta (OI) by dysregulating intracellular calcium flux.
Objectives:
Clinical and bone material phenotype description ...and osteoblast differentiation studies.
Design and Setting:
Natural history study in pediatric research centers.
Patients:
Eight patients with type XIV OI.
Main Outcome Measures:
Clinical examinations included bone mineral density, radiographs, echocardiography, and muscle biopsy. Bone biopsy samples (n = 3) were analyzed using histomorphometry, quantitative backscattered electron microscopy, and Raman microspectroscopy. Cellular differentiation studies were performed on proband and control osteoblasts and normal murine osteoclasts.
Results:
Type XIV OI clinical phenotype ranges from asymptomatic to severe. Previously unreported features include vertebral fractures, periosteal cloaking, coxa vara, and extraskeletal features (muscular hypotonia, cardiac abnormalities). Proband lumbar spine bone density z score was reduced median −3.3 (range −4.77 to +0.1; n = 7) and increased by +1.7 (1.17 to 3.0; n = 3) following bisphosphonate therapy. TMEM38B mutant bone has reduced trabecular bone volume, osteoblast, and particularly osteoclast numbers, with >80% reduction in bone resorption. Bone matrix mineralization is normal and nanoporosity low. We demonstrate a complex osteoblast differentiation defect with decreased expression of early markers and increased expression of late and mineralization-related markers. Predominance of trimeric intracellular cation channel type B over type A expression in murine osteoclasts supports an intrinsic osteoclast defect underlying low bone turnover.
Conclusions:
OI type XIV has a bone histology, matrix mineralization, and osteoblast differentiation pattern that is distinct from OI with collagen defects. Probands are responsive to bisphosphonates and some show muscular and cardiovascular features possibly related to intracellular calcium flux abnormalities.
We describe the clinical and bone material phenotype in type XIV OI. Bone histology, matrix composition, and the osteoblast differentiation pattern is distinct from OI due to collagen defects.
Post-menopausal osteoporosis is characterized by a negative imbalance between bone formation and bone resorption resulting in a net bone loss, increasing the risk of fracture. One of the earliest ...interventions to protect against this was hormonal replacement therapy (HRT).
Bone strength depends on both the amount and quality of bone, the latter including compositional / material and structural properties. Bone compositional / material properties are greatly dependent on both patient-, and tissue-age.
Raman spectroscopy is an analytical tool ideally suited for the determination of bone compositional / material properties as a function of tissue age as it is capable of analyzing areas ~1 × 1 μm2 in tetracycline labeled bone forming areas. Using such analysis of humeri from an ovariectomized primate animal model, we reported that loss of estrogen results in alteration in the mineralization regulation mechanisms by osteoid organic matrix attributes at actively forming bone surfaces. In the present work, we used Raman microspectroscopic techniques to compare osteoid and youngest mineralized tissue composition, as well as relationships between osteoid organic matrix quality and quality attributes of the earliest mineralized tissue in paired iliac crest biopsies obtained from early postmenopausal women before and after two years of HRT therapy. Significant correlations between osteoid proteoglycans, sulfated proteoglycans, pyridinoline, and earliest mineralized tissue mineral content were observed, suggesting that in addition to changes in bone turnover rates, HRT affects the osteoid composition, mineralization regulation mechanisms, and potentially fibrillogenesis.
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