microRNA-324 mediates bone homeostasis and the regulation of osteoblast and osteoclast differentiation and activity

\ua9 2024 The Author(s). MicroRNAs (miRNAs) modulate the expression of other RNA molecules. One miRNA can target many transcripts, allowing each miRNA to play key roles in many biological pathways. Defects in bone homeostasis result in common age-related diseases including osteoporosis. Serum levels of miR-324-3p positively correlate with several features of bone maintenance. In contrast here, using in vivo micro-computed tomography and histology, global miR-324-null mice demonstrated increased bone mineral density and both trabecular and cortical thickness, with effect magnitudes increasing with age. The bone marrow of miR-324-null mice had reduced lipid content while TRAP staining revealed a decrease in osteoclasts, with histomorphometry demonstrating an increased rate of bone formation. Ex vivo assays showed that the high bone mass phenotype of miR-324-null mice resulted from both increased osteoblast activity and decreased osteoclastogenesis. RNA-seq analysis of osteoblasts, osteoclasts and bone marrow macrophages and target validation assays identified that the osteoclast fusion regulator Pin1 and the master osteogenic regulator Runx2 were targets of miR-324-5p in osteoclast lineage cells and osteoblasts, respectively. Indeed, in vitro Runx2 overexpression recapitulated the increased osteogenesis and decreased adipogenesis phenotype observed in vivo by the loss of miR-324. Overall, these data demonstrate the importance of miR-324 in bone homeostasis by regulating aspects of both bone formation and remodelling. Elucidation of pathways regulated by miR-324 offer promise for the treatment of bone diseases such as osteoporosis

A high-coverage draft genome of the mycalesine butterfly Bicyclus anynana

The mycalesine butterfly Bicyclus anynana, the “Squinting bush brown,” is a model organism in the study of lepidopteran ecology, development, and evolution. Here, we present a draft genome sequence for B. anynana to serve as a genomics resource for current and future studies of this important model species. Seven libraries with insert sizes ranging from 350 bp to 20 kb were constructed using DNA from an inbred female and sequenced using both Illumina and PacBio technology; 128 Gb of raw Illumina data was filtered to 124 Gb and assembled to a final size of 475 Mb (∼×260 assembly coverage). Contigs were scaffolded using mate-pair, transcriptome, and PacBio data into 10 800 sequences with an N50 of 638 kb (longest scaffold 5 Mb). The genome is comprised of 26% repetitive elements and encodes a total of 22 642 predicted protein-coding genes. Recovery of a BUSCO set of core metazoan genes was almost complete (98%). Overall, these metrics compare well with other recently published lepidopteran genomes. We report a high-quality draft genome sequence for Bicyclus anynana. The genome assembly and annotated gene models are available at LepBase (http://ensembl.lepbase.org/index.html).Peer reviewe

Olive Oil effectively mitigates ovariectomy-induced osteoporosis in rats

<p>Abstract</p> <p>Background</p> <p>Osteoporosis, a reduction in bone mineral density, represents the most common metabolic bone disease. Postmenopausal women are particularly susceptible to osteoporosis when their production of estrogen declines. For these women, fracture is a leading cause of morbidity and mortality. This study was conducted to evaluate the protective effects of olive oil supplementation against osteoporosis in ovariectomized (OVX) rats.</p> <p>Methods</p> <p>We studied adult female Wistar rats aged 12-14 months, divided into three groups: sham-operated control (SHAM), ovariectomized (OVX), and ovariectomized rats supplemented with extravirgin olive oil (Olive-OVX) orally for 12 weeks; 4 weeks before ovariectomy and 8 weeks after. At the end of the experiment, blood samples were collected. Plasma levels of calcium, phosphorus, alkaline phosphatase (ALP), malondialdehyde (MDA), and nitrates were assayed. Specimens from both the tibia and the liver were processed for light microscopic examination. Histomorphometric analysis of the tibia was also performed.</p> <p>Results</p> <p>The OVX-rats showed a significant decrease in plasma calcium levels, and a significant increase in plasma ALP, MDA, and nitrates levels. These changes were attenuated by olive oil supplementation in the Olive-OVX rats. Light microscopic examination of the tibia of the OVX rats revealed a significant decrease in the cortical bone thickness (CBT) and the trabecular bone thickness (TBT). In addition, there was a significant increase in the osteoclast number denoting bone resorption. In the Olive-OVX rats these parameters were markedly improved as compared to the OVX group. Examination of the liver specimens revealed mononuclear cellular infiltration in the portal areas in the OVX-rats which was not detected in the Olive-OVX rats.</p> <p>Conclusions</p> <p>Olive oil effectively mitigated ovariectomy-induced osteoporosis in rats, and is a promising candidate for the treatment of postmenopausal osteoporosis.</p

Longitudinal peak strain detects a smaller risk area than visual assessment of wall motion in acute myocardial infarction

<p>Abstract</p> <p>Background</p> <p>Opening of an occluded infarct related artery reduces infarct size and improves survival in acute ST-elevation myocardial infarction (STEMI). In this study we performed tissue Doppler analysis (peak strain, displacement, mitral annular movement (MAM)) and compared with visual assessment for the study of the correlation of measurements of global, regional and segmental function with final infarct size and transmurality. In addition, myocardial risk area was determined and a prediction sought for the development of infarct transmurality ≥50%.</p> <p>Methods</p> <p>Twenty six patients with STEMI submitted for primary percutaneous coronary intervention (PCI) were examined with echocardiography on the catheterization table. Four to eight weeks later repeat echocardiography was performed for reassessment of function and magnetic resonance imaging for the determination of final infarct size and transmurality.</p> <p>Results</p> <p>On a global level, wall motion score index (WMSI), ejection fraction (EF), strain, and displacement all showed significant differences (p ≤ 0.001, p ≤ 0.001, p ≤ 0.001 and p = 0.03) between the two study visits, but MAM did not (p = 0.17). On all levels (global, regional and segmental) and both pre- and post PCI, WMSI showed a higher correlation with scar transmurality compared to strain. We found that both strain and WMSI predicted the development of scar transmurality ≥50%, but strain added no significant information to that obtained with WMSI in a logistic regression analysis.</p> <p>Conclusions</p> <p>In patients with acute STEMI, WMSI, EF, strain, and displacement showed significant changes between the pre- and post PCI exam. In a ROC-analysis, strain had 64% sensitivity at 80% specificity and WMSI around 90% sensitivity at 80% specificity for the detection of scar with transmurality ≥50% at follow-up.</p

A microarray analysis of full depth knee cartilage of ovariectomized rats

<p>Abstract</p> <p>Background</p> <p>This short communication focuses the on articular cartilage and the subchondral bone, both of which play important roles in the development of osteoarthritis (OA). There are indications that estrogen-deficiency, as the post-menopausal state, accelerate the development of OA.</p> <p>Findings</p> <p>We investigated, which extracellular matrix (ECM) protein, proteases and different pro-inflammatory factors was up- or down-regulated in the knee joint tissue in response to estrogen-deficiency in rats induced by ovariectomy. These data support previous findings that several metalloproteinases (MMPs) and cysteine proteases are co-regulated with numerous collagens and proteoglycans that are important for cartilage integrity. Furthermore quite a few pro-inflammatory cytokines were regulated by estrogen deprivation.</p> <p>Conclusion</p> <p>We found multiple genes where regulated in the joint by estrogen-deficiency, many of which correspond well with our current knowledge of the pathogenesis of OA. It supports that estrogen-deficiency (e.g. OVX) may accelerate joint deterioration. However, there are also data that draw attention the need for better understanding of the synergy between proteases and tissue turnover.</p

Two decades of ART: improving on success through further research

Since the introduction of the Atraumatic Restorative Treatment (ART) approach over twenty years ago, more than 190 research publications have appeared. The last research agenda defining research priorities for ART was published in 1999. The objective of the present work was to review existing research in the context of future research priorities for ART. MATERIAL AND METHODS: An internet survey was conducted amongst those who had published on ART or were known to be working on the ART approach, to solicit their views as to areas of future ART research. Three broad categories were defined, namely: 1. Basic and laboratory research; 2. Clinical research, and, 3. Community, Public Health, Health Services Research. RESULTS: A 31% response rate was achieved. The study identified a number of new areas of research as well as areas where additional research is required. These are expressed as recommendations for future ART research. CONCLUSIONS: The ART approach is based on a robust, reliable and ever-growing evidence base concerning its clinical applications which indicates that it is a reliable and quality treatment approach. In common with all other oral health care procedures, targeted applied research is required to improve the oral health care offered

Cost-effectiveness of nurse-led self-help for recurrent depression in the primary care setting: design of a pragmatic randomized trial

<p>Abstract</p> <p>Background</p> <p>Major Depressive Disorder is a leading cause of disability, tends to run a recurrent course and is associated with substantial economic costs due to increased healthcare utilization and productivity losses. Interventions aimed at the prevention of recurrences may reduce patients' suffering and costs. Besides antidepressants, several psychological treatments such as preventive cognitive therapy (PCT) are effective in the prevention of recurrences of depression. Yet, many patients find long-term use of antidepressants unattractive, do not want to engage in therapy sessions and in the primary care setting psychologists are often not available. Therefore, it is important to study whether PCT can be used in a nurse-led self-help format in primary care. This study sets out to test the hypothesis that usual care plus nurse-led self-help for recurrent depression in primary care is feasible, acceptable and cost-effective compared to usual care only.</p> <p>Design</p> <p>Patients are randomly assigned to ‘nurse-led self-help treatment plus usual care’ (134 participants) or ‘usual care’ (134 participants). Randomisation is stratified according to the number of previous episodes (2 or 3 previous episodes versus 4 or more). The primary clinical outcome is the cumulative recurrence rate of depression meeting DSM-IV criteria as assessed by the Structured-Clinical-Interview-for-DSM-IV- disorders at one year after completion of the intervention. Secondary clinical outcomes are quality of life, severity of depressive symptoms, co-morbid psychopathology and self-efficacy. As putative effect-moderators, demographic characteristics, number of previous episodes, type of treatment during previous episodes, age of onset, self-efficacy and symptoms of pain and fatigue are assessed. Cumulative recurrence rate ratios are obtained under a Poisson regression model. Number-needed-to-be-treated is calculated as the inverse of the risk-difference. The economic evaluation is conducted from a societal perspective, both as a cost-effectiveness analysis (costs per depression free survival year) and as a cost-utility analysis (costs per quality adjusted life-year).</p> <p>Discussion</p> <p>The purpose of this paper is to outline the rationale and design of a nurse-led, cognitive therapy based self-help aimed at preventing recurrence of depression in a primary care setting. Only few studies have focused on psychological self-help interventions aimed at the prevention of recurrences in primary care patients.</p> <p>Trial registration</p> <p>NTR3001 (<url>http://www.trialregister.nl</url>)</p

Accelerated post traumatic osteoarthritis in a dual injury murine model

Objective: Joint injury involving destabilisation of the joint and damage to the articular cartilage (e.g., sports-related injury) can result in accelerated post-traumatic osteoarthritis (PTOA). Destabilised medial meniscotibial ligament (DMM) surgery is one of the most commonly used murine models and whilst it recapitulates Osteoarthritis (OA) pathology, it does not necessarily result in multi-tissue injury, as occurs in PTOA. We hypothesised that simultaneous cartilage damage and joint destabilisation would accelerate the onset of OA pathology. Methods: OA was induced in C57BL/6 mice via (a) DMM, (b) microblade scratches of articular cartilage (CS) or (c) combined DMM and cartilage scratch (DCS). Mice were culled 7, 14 and 28 days post-surgery. Microcomputed tomography (μCT) and histology were used to monitor bone changes and inflammation. Dynamic weight bearing, an indirect measure of pain, was assessed on day 14. Results: Osteophytogenesis analysis via μCT revealed that osteophytes were present in all groups at days 7 and 14 post-surgery. However, in DCS, osteophytes were visually larger and more numerous when compared with DMM and cartilage scratch (CS). Histological assessment of cartilage at day 14 and 28, revealed significantly greater damage in DCS compared with DMM and CS. Furthermore, a significant increase in synovitis was observed in DCS. Finally, at day 14 osteophyte numbers correlated with changes in dynamic weight bearing. Conclusion: Joint destabilisation when combined with simultaneous cartilage injury accelerates joint deterioration, as seen in PTOA. Thus, DCS provides a novel and robust model for investigating multiple pathological hallmarks, including osteophytogenesis, cartilage damage, synovitis and OA-related pain

A quantitative analysis of the effect of insulin-like growth factor-1 infusion during mandibular distraction osteogenesis in rabbits.

AIM: To quantify, by histomorphometry, the effects of local insulin-like growth factor-1 (IGF-1) during mandibular distraction at various rates. METHODOLOGY: Mature rabbits underwent bilateral mandibular corticotomy and distraction lengthening. Recombinant IGF-1 was administered to two groups of rabbits via osmotic infusion pumps. Distraction regimes were as follows: Group A, 1 mm/day for 15 days; Group B, as for A plus IGF-1; Group C, 3 mm/day for 5 days; Group D, as for C plus IGF-1; and Group E, sham-operated controls. After a 28-day consolidation period, rabbits were sacrificed and bone deposition quantified using DEXA scanning, three-point bending, histological examination and sampled for histomorphometric analysis. RESULTS: DEXA scanning and three-point bending failed to detect any effect of distraction rate or of IGF-1 infusion. Histological and histomorphometric analysis suggested 1 mm/day to be the ideal distraction rate, as this was associated with greater osteoblastic activity and consistent bony union. However, IGF-1 infusion significantly enhanced osteoblastic activity at both distraction rates and resulted in bony union when distraction was performed at 3 mm/day. CONCLUSIONS: Distraction osteogenesis at a rate of 1 mm/day provides greater osteogenic stimulus than 3 mm/day. Exogenous IGF-1 has a positive influence on osteoblastic activity during distraction. Its effect is probably minimised by high levels of endogenous IGF-1