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Trends in Endocrinology and Metabolism:... Jul 2021The development of progressive osteopenia and osteoporosis (OP) is due to the imbalance between bone resorption and bone formation, determining a lower bone resistance,...
The development of progressive osteopenia and osteoporosis (OP) is due to the imbalance between bone resorption and bone formation, determining a lower bone resistance, major risks of fractures, with consequent pain and functional limitations. Flavonoids, a class of polyphenols, have been extensively studied for their therapeutic activities against bone resorption, but less attention has been given to a whole series of molecules belonging to the polyphenolic compounds. However, these classes have begun to be studied for the treatment of OP. In this systematic review, comprehensive information is provided on non-flavonoid polyphenolic compounds, and we highlight pathways implicated in the action of these molecules that act often epigenetically, and their possible use for OP treatment and prevention.
Topics: Bone Resorption; Flavonoids; Humans; Osteogenesis; Osteoporosis; Polyphenols
PubMed: 33895073
DOI: 10.1016/j.tem.2021.03.008 -
Stem Cell Research & Therapy May 2023Human adult dental pulp stem cells (hDPSC) and stem cells from human exfoliated deciduous teeth (SHED) hold promise in bone regeneration for their easy accessibility,... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Human adult dental pulp stem cells (hDPSC) and stem cells from human exfoliated deciduous teeth (SHED) hold promise in bone regeneration for their easy accessibility, high proliferation rate, self-renewal and osteogenic differentiation capacity. Various organic and inorganic scaffold materials were pre-seeded with human dental pulp stem cells in animals, with promising outcomes in new bone formation. Nevertheless, the clinical trial for bone regeneration using dental pulp stem cells is still in its infancy. Thus, the aim of this systematic review and meta-analysis is to synthesise the evidence of the efficacy of human dental pulp stem cells and the scaffold combination for bone regeneration in animal bone defect models.
METHODOLOGY
This study was registered in PROSPERO (CRD2021274976), and PRISMA guideline was followed to include the relevant full-text papers using exclusion and inclusion criteria. Data were extracted for the systematic review. Quality assessment and the risk of bias were also carried out using the CAMARADES tool. Quantitative bone regeneration data of the experimental (scaffold + hDPSC/SHED) and the control (scaffold-only) groups were also extracted for meta-analysis.
RESULTS
Forty-nine papers were included for systematic review and only 27 of them were qualified for meta-analysis. 90% of the included papers were assessed as medium to low risk. In the meta-analysis, qualified studies were grouped by the unit of bone regeneration measurement. Overall, bone regeneration was significantly higher (p < 0.0001) in experimental group (scaffold + hDPSC/SHED) compared to the control group (scaffold-only) (SMD: 1.863, 95% CI 1.121-2.605). However, the effect is almost entirely driven by the % new bone formation group (SMD: 3.929, 95% CI 2.612-5.246) while % BV/TV (SMD: 2.693, 95% CI - 0.001-5.388) shows a marginal effect. Dogs and hydroxyapatite-containing scaffolds have the highest capacity in % new bone formation in response to human DPSC/SHED. The funnel plot exhibits no apparent asymmetry representing a lack of remarkable publication bias. Sensitivity analysis also indicated that the results generated in this meta-analysis are robust and reliable.
CONCLUSION
This is the first synthesised evidence showing that human DPSCs/SHED and scaffold combination enhanced bone regeneration highly significantly compared to the cell-free scaffold irrespective of scaffold type and animal species used. So, dental pulp stem cells could be a promising tool for treating various bone diseases, and more clinical trials need to be conducted to evaluate the effectiveness of dental pulp stem cell-based therapies.
Topics: Adult; Animals; Dogs; Humans; Bone Regeneration; Cell Differentiation; Dental Pulp; Osteogenesis; Stem Cell Transplantation; Tissue Scaffolds
PubMed: 37189187
DOI: 10.1186/s13287-023-03357-w -
Electric/Magnetic Intervention for Bone Regeneration: A Systematic Review and Network Meta-Analysis.Tissue Engineering. Part B, Reviews Jun 2023Electric/magnetic material or field is a promising strategy for bone regeneration. The aim of this systematic review and network meta-analysis was to analyze the... (Meta-Analysis)
Meta-Analysis Review
Electric/magnetic material or field is a promising strategy for bone regeneration. The aim of this systematic review and network meta-analysis was to analyze the evidence regarding the efficacy of electric and magnetic intervention for bone regeneration and provide directions for further research. A comprehensive search was performed to identify the rats/rabbits/mice research that involved the electric/magnetic treatment with quantitative radiographic assessment of bone formation. Network meta-analyses were also conducted to assess different interventions and outcomes for osteogenesis. In total, there were 51 articles included in the systematic review and 19 articles in the network meta-analyses. The majority used microcomputerized tomography bone volume/tissue volume (BV/TV) to evaluate outcomes in rats. Results showed that placing electric/magnetic materials had more prominent effects than the electric/magnetic field on bone regeneration. For all species, electrical materials with zeta potential of -53 mV proved to be the most effective in increasing BV (mean difference [MD]: 4.20 mm, 95% confidence interval [CI]: [1.72-6.68]) and bone mineral density (MD: 312 mg/cm, 95% CI: [172.43-451.57]). Magnetic materials with external magnetic fields topped in BV/TV (MD: 43%, 95% CI: [36.04-49.96]). It also led in trabecular number (MD: 2.00 mm, 95% CI: [1.45-2.55]), trabecular thickness (MD: 61.00 μm, 95% CI: [44.31- 77.69]), and trabecular separation (MD: -0.40 mm, 95% CI: [-0.56 to -0.24]) on the condition of lacking electric materials. Biomaterials implantation is the most effective method for stimulating osteogenesis in rats, especially in electrical materials with negative charge. The combination of diverse interventions shows promising effects but needs further research, so does the underlying mechanism. Impact Statement Bone defect, especially for the large defect from aging, trauma, or pathology, which cannot be completely healed, remains a clinical challenge. Mimicking physical microenvironment has emerged as a new strategy for tissue regeneration. Electric and magnetic material and field used as the physical stimulation for bone regeneration have attracted interest due to their potential and facile application in clinic. This article reviewed related animal studies and carried out a network meta-analysis to thoroughly understand how electric and magnetic interventions impacted on tissues and created an osteogenic microenvironment.
Topics: Rats; Mice; Rabbits; Animals; Network Meta-Analysis; Bone Regeneration; Osteogenesis; Bone and Bones; Magnetic Phenomena
PubMed: 36170583
DOI: 10.1089/ten.TEB.2022.0127 -
Osteoarthritis and Cartilage Jun 2024Clinical Practice Guidelines (CPGs) aim to support management of hip and knee osteoarthritis (OA), but recommendations are often conflicting and implementation is poor,... (Review)
Review
OBJECTIVE
Clinical Practice Guidelines (CPGs) aim to support management of hip and knee osteoarthritis (OA), but recommendations are often conflicting and implementation is poor, contributing to evidence-to-practice gaps. This systematic review investigated the contextual and methodological factors contributing to conflicting recommendations for hip and knee OA.
METHOD
Our systematic review appraised CPGs for managing hip and knee OA in adults ≥18 years (PROSPERO CRD42021276635). We used AGREE-II and AGREE-REX to assess quality and extracted data on treatment gaps, conflicts, biases, and consensus. Heterogeneity of recommendations was determined using Weighted Fleiss Kappa (K). The relationship between (K) and AGREE-II/AGREE-REX scores was explored.
RESULTS
We identified 25 CPGs across eight countries and four international organisations. The ACR, EULAR, NICE, OARSI and RACGP guidelines scored highest for overall AGREE-II quality (83%). The highest overall AGREE-REX scores were for BMJ Arthroscopy (80%), RACGP (78%) and NICE (76%). CPGs with the least agreement for pharmacological recommendations were ESCEO and NICE (-0.14), ACR (-0.08), and RACGP (-0.01). The highest agreements were between RACGP and NICE (0.53), RACGP and ACR (0.61), and NICE and ACR (0.91). Decreased internal validity determined by low-quality AGREE scores(<60%) in editorial independence were associated with less agreement for pharmacological recommendations.
CONCLUSION
There were associations between guideline quality and agreement scores. Future guideline development should be informed by robust evidence, editorial independence and methodological rigour to ensure a harmonisation of recommendations. End-users of CPGs must recognise the contextual factors associated with the development of OA CPGs and balance these factors with available evidence.
Topics: Humans; Practice Guidelines as Topic; Osteoarthritis, Hip; Osteoarthritis, Knee; Evidence-Based Medicine
PubMed: 38452880
DOI: 10.1016/j.joca.2024.02.890 -
Journal of Cellular and Molecular... Feb 2022Fracture non-union represents a common complication, seen in 5%-10% of all acute fractures. Despite the enhancement in scientific understanding and treatment methods,... (Review)
Review
Fracture non-union represents a common complication, seen in 5%-10% of all acute fractures. Despite the enhancement in scientific understanding and treatment methods, rates of fracture non-union remain largely unchanged over the years. This systematic review investigates the biological, molecular and genetic profiles of both (i) non-union tissue and (ii) non-union-related tissues, and the genetic predisposition to fracture non-union. This is crucially important as it could facilitate earlier identification and targeted treatment of high-risk patients, along with improving our understanding on pathophysiology of fracture non-union. Since this is an update on our previous systematic review, we searched the literature indexed in PubMed Medline; Ovid Medline; Embase; Scopus; Google Scholar; and the Cochrane Library using Medical Subject Heading (MeSH) or Title/Abstract words (non-union(s), non-union(s), human, tissue, bone morphogenic protein(s) (BMPs) and MSCs) from August 2014 (date of our previous publication) to 2 October 2021 for non-union tissue studies, whereas no date restrictions imposed on non-union-related tissue studies. Inclusion criteria of this systematic review are human studies investigating the characteristics and properties of non-union tissue and non-union-related tissues, available in full-text English language. Limitations of this systematic review are exclusion of animal studies, the heterogeneity in the definition of non-union and timing of tissue harvest seen in the included studies, and the search term MSC which may result in the exclusion of studies using historical terms such as 'osteoprogenitors' and 'skeletal stem cells'. A total of 24 studies (non-union tissue: n = 10; non-union-related tissues: n = 14) met the inclusion criteria. Soft tissue interposition, bony sclerosis of fracture ends and complete obliteration of medullary canal are commonest macroscopic appearances of non-unions. Non-union tissue colour and surrounding fluid are two important characteristics that could be used clinically to distinguish between septic and aseptic non-unions. Atrophic non-unions had a predominance of endochondral bone formation and lower cellular density, when compared against hypertrophic non-unions. Vascular tissues were present in both atrophic and hypertrophic non-unions, with no difference in vessel density between the two. Studies have found non-union tissue to contain biologically active MSCs with potential for osteoblastic, chondrogenic and adipogenic differentiation. Proliferative capacity of non-union tissue MSCs was comparable to that of bone marrow MSCs. Rates of cell senescence of non-union tissue remain inconclusive and require further investigation. There was a lower BMP expression in non-union site and absent in the extracellular matrix, with no difference observed between atrophic and hypertrophic non-unions. The reduced BMP-7 gene expression and elevated levels of its inhibitors (Chordin, Noggin and Gremlin) could potentially explain impaired bone healing observed in non-union MSCs. Expression of Dkk-1 in osteogenic medium was higher in non-union MSCs. Numerous genetic polymorphisms associated with fracture non-union have been identified, with some involving the BMP and MMP pathways. Further research is required on determining the sensitivity and specificity of molecular and genetic profiling of relevant tissues as a potential screening biomarker for fracture non-unions.
Topics: Animals; Bone Morphogenetic Proteins; Fracture Healing; Fractures, Bone; Fractures, Ununited; Genetic Predisposition to Disease; Humans; Osteogenesis
PubMed: 34984803
DOI: 10.1111/jcmm.17096 -
Molecular Psychiatry Oct 2023Adolescence represents a critical period for brain and behavioural health and characterised by the onset of mood, psychotic and anxiety disorders. In rodents,...
Adolescence represents a critical period for brain and behavioural health and characterised by the onset of mood, psychotic and anxiety disorders. In rodents, neurogenesis is very active during adolescence, when is particularly vulnerable to stress. Whether stress-related neurogenesis changes influence adolescence onset of psychiatric symptoms remains largely unknown. A systematic review was conducted on studies investigating changes in hippocampal neurogenesis and neuroplasticity, hippocampal-dependent cognitive functions, and behaviour, occurring after adolescence stress exposure in mice both acutely (at post-natal days 21-65) and in adulthood. A total of 37 studies were identified in the literature. Seven studies showed reduced hippocampal cell proliferation, and out of those two reported increased depressive-like behaviours, in adolescent rodents exposed to stress. Three studies reported a reduction in the number of new-born neurons, which however were not associated with changes in cognition or behaviour. Sixteen studies showed acutely reduced hippocampal neuroplasticity, including pre- and post-synaptic plasticity markers, dendritic spine length and density, and long-term potentiation after stress exposure. Cognitive impairments and depressive-like behaviours were reported by 11 of the 16 studies. Among studies who looked at adolescence stress exposure effects into adulthood, seven showed that the negative effects of stress observed during adolescence on either cell proliferation or hippocampal neuroplasticity, cognitive deficits and depressive-like behaviour, had variable impact in adulthood. Treating adolescent mice with antidepressants, glutamate receptor inhibitors, glucocorticoid antagonists, or healthy diet enriched in omega-3 fatty acids and vitamin A, prevented or reversed those detrimental changes. Future research should investigate the translational value of these preclinical findings. Developing novel tools for measuring hippocampal neurogenesis in live humans, would allow assessing neurogenic changes following stress exposure, investigating relationships with psychiatric symptom onset, and identifying effects of therapeutic interventions.
Topics: Animals; Mice; Brain; Cognition; Hippocampus; Neurogenesis; Rodentia; Stress, Psychological
PubMed: 37612364
DOI: 10.1038/s41380-023-02229-2 -
Behavioral and Brain Functions : BBF May 2022Genetic variants of DCX, COMT and FMR1 have been linked to neurodevelopmental disorders related to intellectual disability and social behavior. In this systematic review... (Review)
Review
Genetic variants of DCX, COMT and FMR1 have been linked to neurodevelopmental disorders related to intellectual disability and social behavior. In this systematic review we examine the roles of the DCX, COMT and FMR1 genes in the context of hippocampal neurogenesis with respect to these disorders with the aim of identifying important hubs and signaling pathways that may bridge these conditions. Taken together our findings indicate that factors connecting DCX, COMT, and FMR1 in intellectual disability and social behavior may converge at Wnt signaling, neuron migration, and axon and dendrite morphogenesis. Data derived from genomic research has identified a multitude of genes that are linked to brain disorders and developmental differences. Information about where and how these genes function and cooperate is lagging behind. The approach used here may help to shed light on the biological underpinnings in which key genes interface and may prove useful for the testing of specific hypotheses.
Topics: Catechol O-Methyltransferase; Cognitive Dysfunction; Fragile X Mental Retardation Protein; Hippocampus; Humans; Intellectual Disability; Neurogenesis; Social Behavior
PubMed: 35590332
DOI: 10.1186/s12993-022-00191-7 -
International Journal of Oral and... Apr 2017Nicotine has been associated with vasoconstriction and an impaired cellular healing response. It is therefore likely that nicotine jeopardizes osseointegration. This... (Meta-Analysis)
Meta-Analysis Review
Nicotine has been associated with vasoconstriction and an impaired cellular healing response. It is therefore likely that nicotine jeopardizes osseointegration. This systematic review and meta-analysis was performed to assess pre-clinical studies on the effect of nicotine on implant osseointegration. Databases were searched up to and including March 2016 for animal/non-human studies using the following Keywords: bone to implant contact; implant; nicotine; osseointegration; bone healing; and new bone formation. In total eight in vivo design studies were included and processed for data extraction. Five studies reported no significant influence of nicotine on healing around implants. Quantitative analysis of the effects of nicotine on the osseointegration of dental implants showed a significant difference in bone-to-implant contact between test and control subjects (Z=-2.49; P=0.014). From the studies included in the present review; it appears that nicotine has an effect on implant osseointegration.
Topics: Animals; Dental Implantation, Endosseous; Dental Implants; Nicotine; Osseointegration; Osteogenesis; Wound Healing
PubMed: 28189374
DOI: 10.1016/j.ijom.2016.12.003 -
Tissue Engineering. Part B, Reviews Oct 2017The regeneration of bone defects resulting from trauma, resection of tumors, infection, or congenital disease is a challenge, and bone grafts are utilized in a wide... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The regeneration of bone defects resulting from trauma, resection of tumors, infection, or congenital disease is a challenge, and bone grafts are utilized in a wide array of clinical settings to augment bone repair and regeneration. Diabetes mellitus (DM) is a chronic metabolic disease, which affects 8.3% of the world population, summing ∼387 million individuals. The consequences of the disease, for example, hyperglycemia, have been associated to a reduced capacity to form bone and poor bone quality, influencing bone healing. Our aim was to systematically review the literature to the effect of diabetic condition on bone regeneration in animal models, when using bone substitute materials from different origins, and perform a meta-analysis to quantitatively study the effect of DM on bone regeneration.
METHODS
An extensive search strategy was carried out through PubMed and EMBASE to identify the potential relevant studies published from database inception until July 1, 2015. Initially, the title and abstract of 1409 studies were screened, after which inclusion criteria sorted 29 studies for full-text evaluation. After using exclusion criteria, a final number of seven studies could be included in the review.
RESULTS
The seven included studies that passed our inclusion/exclusion criteria were all type 1 diabetes, comprising a total of 189 animals and 14 intrastudy comparisons. These studies presented a consistent and reduced risk of bias and showed a significant average effect size of -6.87% of bone formation for diabetes type 1 versus healthy condition [95% confidence interval: -10.55 to -3.18; I = 87.4%; p = 0.0003].
INTERPRETATION
These findings prove that DM type 1 negatively influences bone formation compared with a healthy condition, irrespective of the bone substitute material used.
Topics: Animals; Bone Regeneration; Diabetes Mellitus; Humans; Osteogenesis; Outcome Assessment, Health Care; Prosthesis Implantation; Publication Bias
PubMed: 27981888
DOI: 10.1089/ten.TEB.2016.0370 -
Seminars in Cell & Developmental Biology May 2023Normal axon development depends on the action of mechanical forces both generated within the cytoskeleton and outside the cell, but forces of large magnitude or rate... (Review)
Review
Normal axon development depends on the action of mechanical forces both generated within the cytoskeleton and outside the cell, but forces of large magnitude or rate cause damage instead. Computational models aid scientists in studying the role of mechanical forces in axon growth and damage. These studies use simulations to evaluate how different sources of force generation within the cytoskeleton interact with each other to regulate axon elongation and retraction. Furthermore, mathematical models can help optimize externally applied tension to promote axon growth without causing damage. Finally, scientists also use simulations of axon damage to investigate how forces are distributed among different components of the axon and how the tissue surrounding an axon influences its susceptibility to injury. In this review, we discuss how computational studies complement experimental studies in the areas of axon growth, regeneration, and damage.
Topics: Axons; Cytoskeleton; Microtubules; Neurogenesis; Computer Simulation
PubMed: 35474150
DOI: 10.1016/j.semcdb.2022.04.019