scholarly journals The Crossroads between Infection and Bone Loss

2020 ◽  
Vol 8 (11) ◽  
pp. 1765 ◽  
Author(s):  
Tiago Carvalho Oliveira ◽  
Maria Salomé Gomes ◽  
Ana Cordeiro Gomes
Keyword(s):  
Bone Loss ◽  
Bone Metabolism ◽  
Chronic Infection ◽  
The Other ◽  
Bone Homeostasis ◽  
Immune Mediators ◽  
Bone Degradation ◽  
Indirect Consequence ◽  
Mineral Matrix ◽  
The Impact

Bone homeostasis, based on a tight balance between bone formation and bone degradation, is affected by infection. On one hand, some invading pathogens are capable of directly colonizing the bone, leading to its destruction. On the other hand, immune mediators produced in response to infection may dysregulate the deposition of mineral matrix by osteoblasts and/or the resorption of bone by osteoclasts. Therefore, bone loss pathologies may develop in response to infection, and their detection and treatment are challenging. Possible biomarkers of impaired bone metabolism during chronic infection need to be identified to improve the diagnosis and management of infection-associated osteopenia. Further understanding of the impact of infections on bone metabolism is imperative for the early detection, prevention, and/or reversion of bone loss. Here, we review the mechanisms responsible for bone loss as a direct and/or indirect consequence of infection.

scholarly journals Dietary Salt Accelerates Orthodontic Tooth Movement by Increased Osteoclast Activity

2021 ◽  
Vol 22 (2) ◽  
pp. 596
Author(s):  
Agnes Schröder ◽  
Joshua Gubernator ◽  
Alexandra Leikam ◽  
Ute Nazet ◽  
Fabian Cieplik ◽  
...  
Keyword(s):  
Bone Density ◽  
Bone Loss ◽  
Bone Metabolism ◽  
Tooth Movement ◽  
Orthodontic Tooth Movement ◽  
Dietary Salt ◽  
Osteoclast Activity ◽  
Salt Uptake ◽  
Periodontal Bone Loss ◽  
The Impact

Dietary salt uptake and inflammation promote sodium accumulation in tissues, thereby modulating cells like macrophages and fibroblasts. Previous studies showed salt effects on periodontal ligament fibroblasts and on bone metabolism by expression of nuclear factor of activated T-cells-5 (NFAT-5). Here, we investigated the impact of salt and NFAT-5 on osteoclast activity and orthodontic tooth movement (OTM). After treatment of osteoclasts without (NS) or with additional salt (HS), we analyzed gene expression and the release of tartrate-resistant acid phosphatase and calcium phosphate resorption. We kept wild-type mice and mice lacking NFAT-5 in myeloid cells either on a low, normal or high salt diet and inserted an elastic band between the first and second molar to induce OTM. We analyzed the expression of genes involved in bone metabolism, periodontal bone loss, OTM and bone density. Osteoclast activity was increased upon HS treatment. HS promoted periodontal bone loss and OTM and was associated with reduced bone density. Deletion of NFAT-5 led to increased osteoclast activity with NS, whereas we detected impaired OTM in mice. Dietary salt uptake seems to accelerate OTM and induce periodontal bone loss due to reduced bone density, which may be attributed to enhanced osteoclast activity. NFAT-5 influences this reaction to HS, as we detected impaired OTM and osteoclast activity upon deletion.

scholarly journals Serum Levels of miR-148a and miR-21-5p Are Increased in Type 1 Diabetic Patients and Correlated with Markers of Bone Strength and Metabolism

2018 ◽  
Vol 4 (4) ◽  
pp. 37 ◽  
Author(s):  
Giuseppina E. Grieco ◽  
Dorica Cataldo ◽  
Elena Ceccarelli ◽  
Laura Nigi ◽  
Giovanna Catalano ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Type 1 Diabetes ◽  
Bone Loss ◽  
Bone Metabolism ◽  
Bone Remodeling ◽  
Bone Mineral ◽  
Bone Fragility ◽  
Bone Homeostasis ◽  
Mineral Density

Type 1 diabetes (T1D) is characterized by bone loss and altered bone remodeling, resulting into reduction of bone mineral density (BMD) and increased risk of fractures. Identification of specific biomarkers and/or causative factors of diabetic bone fragility is of fundamental importance for an early detection of such alterations and to envisage appropriate therapeutic interventions. MicroRNAs (miRNAs) are small non-coding RNAs which negatively regulate genes expression. Of note, miRNAs can be secreted in biological fluids through their association with different cellular components and, in such context, they may represent both candidate biomarkers and/or mediators of bone metabolism alterations. Here, we aimed at identifying miRNAs differentially expressed in serum of T1D patients and potentially involved in bone loss in type 1 diabetes. We selected six miRNAs previously associated with T1D and bone metabolism: miR-21; miR-24; miR-27a; miR-148a; miR-214; and miR-375. Selected miRNAs were analyzed in sera of 15 T1D patients (age: 33.57 ± 8.17; BMI: 21.4 ± 1.65) and 14 non-diabetic subjects (age: 31.7 ± 8.2; BMI: 24.6 ± 4.34). Calcium, osteocalcin, parathormone (PTH), bone ALkaline Phoshatase (bALP), and Vitamin D (VitD) as well as main parameters of bone health were measured in each patient. We observed an increased expression of miR-148a (p = 0.012) and miR-21-5p (p = 0.034) in sera of T1D patients vs non-diabetic subjects. The correlation analysis between miRNAs expression and the main parameters of bone metabolism, showed a correlation between miR-148a and Bone Mineral Density (BMD) total body (TB) values (p = 0.042) and PTH circulating levels (p = 0.033) and the association of miR-21-5p to Bone Mineral Content-Femur (BMC-FEM). Finally, miR-148a and miR-21-5p target genes prediction analysis revealed several factors involved in bone development and remodeling, such as MAFB, WNT1, TGFB2, STAT3, or PDCD4, and the co-modulation of common pathways involved in bone homeostasis thus potentially assigning a role to both miR-148a and miR-21-5p in bone metabolism alterations. In conclusion, these results lead us to hypothesize a potential role for miR-148a and miR-21-5p in bone remodeling, thus representing potential biomarkers of bone fragility in T1D.

scholarly journals Roles for B[a]P and FICZ in subchondral bone metabolism and experimental temporomandibular joint osteoarthritis via the AhR/Cyp1a1 signaling axis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuri Yoshikawa ◽  
Takashi Izawa ◽  
Yusaku Hamada ◽  
Hiroko Takenaga ◽  
Ziyi Wang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Mouse Model ◽  
Bone Metabolism ◽  
Temporomandibular Joint ◽  
Subchondral Bone ◽  
Dependent Manner ◽  
Bone Homeostasis ◽  
Wild Type ◽  
Temporomandibular Joint Osteoarthritis ◽  
Signaling Axis

AbstractBone loss due to smoking represents a major risk factor for fractures and bone osteoporosis. Signaling through the aryl hydrocarbon receptor (AhR) and its ligands contributes to both bone homeostasis and inflammatory diseases. It remains unclear whether the same AhR signaling axis affects the temporomandibular joint (TMJ). The aim of this study was to investigate possible mechanisms which mediate bone loss in the TMJ due to smoking. In particular, whether benzo[a]pyrene (B[a]P), a carcinogen of tobacco smoke, induces expression of the AhR target gene, Cyp1a1, in mandibular condyles. Possible functions of an endogenous ligand of FICZ, were also investigated in a TMJ-osteoarthritis (OA) mouse model. B[a]P was administered orally to wild-type and AhR−/− mice and bone metabolism was subsequently examined. TMJ-OA was induced in wild-type mice with forceful opening of the mouth. Therapeutic functions of FICZ were detected with μCT and histology. Exposure to B[a]P accelerated bone loss in the mandibular subchondral bone. This bone loss manifested with osteoclastic bone resorption and upregulated expression of Cyp1a1 in an AhR-dependent manner. In a mouse model of TMJ-OA, FICZ exhibited a dose-dependent rescue of mandibular subchondral bone loss by repressing osteoclast activity. Meanwhile, in vitro, pre-treatment with FICZ reduced RANKL-mediated osteoclastogenesis. B[a]P regulates mandibular subchondral bone metabolism via the Cyp1a1. The AhR ligand, FICZ, can prevent TMJ-OA by regulating osteoclast differentiation.

scholarly journals The Impact of Microgravity on Bone Metabolism in vitro and in vivo

2001 ◽  
Vol 12 (3) ◽  
pp. 252-261 ◽  
Author(s):  
Peter M. Loomer
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Bone Metabolism ◽  
Bone Cells ◽  
Mechanical Load ◽  
Space Environment ◽  
In Vivo Studies ◽  
The Impact

Exposure to microgravity has been associated with several physiological changes in astronauts and cosmonauts, including an osteoporosis-like loss of bone mass. In-flight measures used to counteract this, including intensive daily exercise regimens, have been only partially successful in reducing the bone loss and in the process have consumed valuable work time. If this bone loss is to be minimized or, preferably, prevented, more effective treatment strategies are required. This, however, requires a greater understanding of the mechanisms through which bone metabolism is affected by microgravity. Various research strategies have been used to examine this problem, including in vitro studies using bone cells and in vivo studies on humans and rats. These have been conducted both in flight and on the ground, by strategies that produce weightlessness to mimic the effects of microgravity. Overall, the majority of the studies have found that marked decreases in gravitation loading result in the loss of bone mass. The processes of bone formation and bone resorption become uncoupled, with an initial transitory increase in resorption accompanied by a prolonged decrease in formation. Loss of bone mass is not uniform throughout the skeleton, but varies at different sites depending on the type of bone and on the mechanical load received. It appears that the skeletal response is a physiologic adaptation to the space environment which, after long space flights or repeated shorter ones, could eventually lead to significant reductions in the ability of the skeletal tissues to withstand the forces of gravity and increased susceptibility to fracture.

scholarly journals Skeletal inflammation and attenuation of Wnt signaling, Wnt ligand expression, and bone formation in atherosclerotic ApoE-null mice

2016 ◽  
Vol 310 (9) ◽  
pp. E762-E773 ◽  
Author(s):  
Yu Liu ◽  
Maria Almeida ◽  
Robert S. Weinstein ◽  
Charles A. O'Brien ◽  
Stavros C. Manolagas ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Mass ◽  
Wnt Signaling ◽  
Cortical Bone ◽  
Oxidized Lipids ◽  
Bone Homeostasis ◽  
Wnt Ligands ◽  
Apoe Ko Mice ◽  
The Impact ◽  
Apoe Ko

ApoE-null (ApoE-KO) mice fed a high-fat diet (HFD) develop atherosclerosis, due in part to activation of vascular inflammation by oxidized low-density lipoprotein. Since bone loss also occurs in these mice, we used them to investigate the impact of oxidized lipids on bone homeostasis and to search for underlying pathogenic pathways. Four-month-old female ApoE-KO mice fed a HFD for three months exhibited increased levels of oxidized lipids in bone, as well as decreased femoral and vertebral trabecular and cortical bone mass, compared with ApoE-KO mice on normal diet. Despite HFD-induced increase in expression of Alox15, a lipoxygenase that oxidizes LDL and promotes atherogenesis, global deletion of this gene failed to ameliorate the skeletal impact of HFD. Osteoblast number and function were dramatically reduced in trabecular and cortical bone of HFD-fed mice, whereas osteoclast number was modestly reduced only in trabecular bone, indicating that an imbalance in favor of osteoclasts was responsible for HFD-induced bone loss. These changes were associated with decreased osteoblast progenitors and increased monocyte/macrophages in the bone marrow as well as increased expression of IL-1β, IL-6, and TNF. HFD also attenuated Wnt signaling as evidenced by reduced expression of Wnt target genes, and it decreased expression of pro-osteoblastogenic Wnt ligands. These results suggest that oxidized lipids decrease bone mass by increasing anti-osteoblastogenic inflammatory cytokines and decreasing pro-osteoblastogenic Wnt ligands.

scholarly journals Bone metabolism: a note on the significance of mouse models

2009 ◽  
pp. 459-471
Author(s):  
O Raška ◽  
K Bernášková ◽  
I Raška
Keyword(s):  
Bone Metabolism ◽  
Mouse Models ◽  
Treatment Strategies ◽  
The Other ◽  
Endocrine Organ ◽  
Obesity And Diabetes ◽  
Long Duration ◽  
Experimental Mouse ◽  
The Impact ◽  
Genetically Modified Animals

This minireview briefly surveys the complexity of regulations governing the bone metabolism. The impact of clinical studies devoted to osteoporosis is briefly summarized and the emphasis is put on the significance of experimental mouse models based on an extensive use of genetically modified animals. Despite possible arising drawbacks, the studies in mice are of prime importance for expanding our knowledge on bone metabolism. With respect to human physiology and medicine, one should be always aware of possible limitations as the experimental results may not be, or may be only to some extent, transposed to humans. If applicable to humans, results obtained in mice provide new clues for assessing unforeseen treatment strategies for patients. A recent publication representing in our opinion the important breakthrough in the field of bone metabolism in mice is commented in detail. It provides an evidence that skeleton is endocrine organ that affects energy metabolism and osteocalcin, a protein specifically synthesized and secreted by osteoblasts, is a hormone involved. If confirmed by other groups and applicable to humans, this study provides the awaited connection of long duration between bone disorders on one hand and obesity and diabetes on the other.

Effect of monthly oral ibandronate on anastrozole-induced bone loss during adjuvant treatment for breast cancer: One-year results from the ARIBON study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 553-553 ◽  
Author(s):  
J. E. Lester ◽  
S. A. Gutcher ◽  
S. P. Ellis ◽  
R. Thorpe ◽  
J. M. Horsman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lumbar Spine ◽  
Bone Loss ◽  
Bone Metabolism ◽  
Biochemical Markers ◽  
Controlled Study ◽  
Breast Cancer Patients ◽  
Mineral Density ◽  
Double Blind ◽  
The Impact

553 Background: The aromatase inhibitor anastrozole is a highly effective treatment for breast cancer with superior efficacy and tolerability advantages over tamoxifen. However its use is associated with significant declines in bone mineral density (BMD) with an increase in fracture risk. The ARIBON trial is a double blind, randomised, placebo-controlled study designed to evaluate the impact of bisphosphonate treatment on BMD in women taking anastrozole. The study also aims to explore the relationship between levels of biochemical markers of bone metabolism with longer term changes in BMD as measured by Dual energy Xray Absorptiometry (DXA). Methods: 131 postmenopausal, surgically treated breast cancer patients were recruited from oncology clinics in Leeds and Sheffield, UK. Following consent, baseline bone densitometry showed that 68, 50 and 13 patients were found to be normal (T >-1.0), osteopenic (T -1.0 to -2.5) and osteoporotic (T < -2.5) respectively. All patients were treated with anastrozole 1mg once a day and offered calcium and vitamin D supplementation. In addition, osteopenic patients were randomised on a 1:1 basis to receive either treatment with ibandronate 150 mg orally every month or placebo. Osteoporotic patients were treated with open label ibandronate orally 150mg every month. Results: After I year, osteopenic patients treated with ibandronate gained +2.78% (range -3.8, +15.1) and +1.35% (range -4.1, +5.6) at the lumbar spine and hip respectively. Patients treated with placebo however lost -2.61% (range -11.0, +2.2) at the lumbar spine and -2.34% (range -10.4, +5.2) at the hip. The differences between the two treatment arms were statistically significant at both sites (p<0.001, independent samples t-test). Patients with osteoporosis gained +5.05% (range -8.7, +15.2) at the lumbar spine and +2.62% (range -1.0, +8.6) at the hip after 1 year. Conclusions: Ibandronate 150 mg by mouth once a month prevents anastrozole induced bone loss and results in significant increases in BMD at the hip and lumbar spine in osteopenic and osteoporotic patients. Analysis of the biochemical markers of bone metabolism is underway and relationships between biochemical and BMD changes will be presented. No significant financial relationships to disclose.

Bone Disruption and Environmental Pollutants

2021 ◽  
Vol 21 ◽  
Author(s):  
Raffaele Giannattasio ◽  
Giuseppe Lisco ◽  
Vito Angelo Giagulli ◽  
Silvio Settembrini ◽  
Giovanni De Pergola ◽  
...  
Keyword(s):  
Bone Metabolism ◽  
Environmental Pollutants ◽  
Free Text ◽  
Bone Homeostasis ◽  
Medical Subject Headings ◽  
Mineral Density ◽  
Hormonal Imbalance ◽  
The Impact ◽  
Final Effect

Background: Endocrine Disrupting Chemicals (EDCs) are ubiquitous and may significantly contribute in environmental pollution, thus contaminating humans and wildlife. Environmental pollutants could interfere with bone homeostasis by means of different mechanisms, which include hormonal imbalance, direct osteoblasts toxicity and enanchment of osteoclasts activity, thus leading to osteopenia or osteoporosis. Among these, bisphenols, dioxins, polycyclic aromatic hydrocarbons, polychlorobiphenyls, poly- and perfluoroalkyls, phthalates, parabens, organotins and cadmium may play a role in bone distuption. Methods: PubMed/MEDLINE, ISI-web of knowledge and Google scholar databases were searched for medical subject headings terms and free-text word related to the aforementioned classes of chemicals and bone metabolism and remodelling for better clarifying and understanding the main mechanisms of bone disruption. Results: Several of EDCs act as xenoestrogens. Considering that estrogens play a significant role in regulating bone remodeling, most of these chemicals generate hormonal imbalance with possible detrimental consequences on bone tissue structure and its mechanical and non-mechanical properties. Discussion: A lot of evidences about bone distruptors came from in vitro studies or animal models, and conduct to equivocal results. In addition, a few data derived form humans and most of these data focused on the impact of EDCs on bone mineral density without considering their influence on long-term fracture risk. Moreover, it should be taken into account that humans are exposed to a mixture of EDCs and the final effect on bone metabolism might be the result of either a synergism or antagonist effects among them. Age of first exposure, cumulative dose exposure over time, and the usually observed non-monotonic dose-response curve for EDCs should be considered as other important variable influencing the final effect on bone metabolism. Conclusion: Taking into account these variables, observational studies are needed to better analyze this issue both for echological purpose and to preserve bone health.

Modernism, Empiricism, and Rationalism

2016 ◽  
Vol 46 (1) ◽  
pp. 38-47
Author(s):  
Geoffrey Squires
Keyword(s):  
Twentieth Century ◽  
The Other ◽  
Modern Poetry ◽  
Philosophical Perspective ◽  
Irish Poetry ◽  
Dimensional Spectrum ◽  
Culture History ◽  
The World ◽  
The Impact ◽  
Rule Out

Modernism is usually defined historically as the composite movement at the beginning of the twentieth century which led to a radical break with what had gone before in literature and the other arts. Given the problems of the continuing use of the concept to cover subsequent writing, this essay proposes an alternative, philosophical perspective which explores the impact of rationalism (what we bring to the world) on the prevailing empiricism (what we take from the world) of modern poetry, which leads to a concern with consciousness rather than experience. This in turn involves a re-conceptualisation of the lyric or narrative I, of language itself as a phenomenon, and of other poetic themes such as nature, culture, history, and art. Against the background of the dominant empiricism of modern Irish poetry as presented in Crotty's anthology, the essay explores these ideas in terms of a small number of poets who may be considered modernist in various ways. This does not rule out modernist elements in some other poets and the initial distinction between a poetics of experience and one of consciousness is better seen as a multi-dimensional spectrum that requires further, more detailed analysis than is possible here.

Sign in / Sign up

Export Citation Format

Share Document