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PloS One 2021Drug research with animal models is expensive, time-consuming and translation to clinical trials is often poor, resulting in a desire to replace, reduce, and refine the...
Drug research with animal models is expensive, time-consuming and translation to clinical trials is often poor, resulting in a desire to replace, reduce, and refine the use of animal models. One approach to replace and reduce the use of animal models is to use in vitro cell-culture models. To study bone physiology, bone diseases and drugs, many studies have been published using osteoblast-osteoclast co-cultures. The use of osteoblast-osteoclast co-cultures is usually not clearly mentioned in the title and abstract, making it difficult to identify these studies without a systematic search and thorough review. As a result, researchers are all developing their own methods, leading to conceptually similar studies with many methodological differences and, as a consequence, incomparable results. The aim of this study was to systematically review existing osteoblast-osteoclast co-culture studies published up to 6 January 2020, and to give an overview of their methods, predetermined outcome measures (formation and resorption, and ALP and TRAP quantification as surrogate markers for formation and resorption, respectively), and other useful parameters for analysis. Information regarding these outcome measures was extracted and collected in a database, and each study was further evaluated on whether both the osteoblasts and osteoclasts were analyzed using relevant outcome measures. From these studies, additional details on methods, cells and culture conditions were extracted into a second database to allow searching on more characteristics. The two databases presented in this publication provide an unprecedented amount of information on cells, culture conditions and analytical techniques for using and studying osteoblast-osteoclast co-cultures. They allow researchers to identify publications relevant to their specific needs and allow easy validation and comparison with existing literature. Finally, we provide the information and tools necessary for others to use, manipulate and expand the databases for their needs.
Topics: Animals; Bone Resorption; Cell Differentiation; Coculture Techniques; Databases, Factual; Drug Discovery; Humans; Models, Animal; Osteoblasts; Osteoclasts; RANK Ligand
PubMed: 34735456
DOI: 10.1371/journal.pone.0257724 -
Bone & Joint Research Sep 2023Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the...
Osteoarthritis (OA) is mainly caused by ageing, strain, trauma, and congenital joint abnormalities, resulting in articular cartilage degeneration. During the pathogenesis of OA, the changes in subchondral bone (SB) are not only secondary manifestations of OA, but also an active part of the disease, and are closely associated with the severity of OA. In different stages of OA, there were microstructural changes in SB. Osteocytes, osteoblasts, and osteoclasts in SB are important in the pathogenesis of OA. The signal transduction mechanism in SB is necessary to maintain the balance of a stable phenotype, extracellular matrix (ECM) synthesis, and bone remodelling between articular cartilage and SB. An imbalance in signal transduction can lead to reduced cartilage quality and SB thickening, which leads to the progression of OA. By understanding changes in SB in OA, researchers are exploring drugs that can regulate these changes, which will help to provide new ideas for the treatment of OA.
PubMed: 37678837
DOI: 10.1302/2046-3758.129.BJR-2023-0081.R1 -
BMC Oral Health Jun 2023Pro- and anti-inflammatory cytokines are acknowledged, during inflammatory bone destruction, as key regulators of osteoclast and osteoblast differentiation and activity.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pro- and anti-inflammatory cytokines are acknowledged, during inflammatory bone destruction, as key regulators of osteoclast and osteoblast differentiation and activity. However, evidence regarding the exact role of pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors in peri-implant diseases is unclear. We aimed to execute a systematic review and meta-analysis about the pro- and anti-inflammatory cytokines and osteoclastogenesis-related factors levels in peri-implant diseases.
METHODS
The focused question was elaborated to summarize the levels of pro-and anti-inflammatory cytokines and osteoclastogenesis-related factors in tissue samples (mRNA) and biofluids (protein levels) of patients with/without peri-implant diseases. Electronic searches of the PubMed, Cochrane Controlled Trials Registry, Web of Science, EMBASE, Scopus and Google scholar databases were conducted for publications up to March 2023. Meta-analysis evaluating the mediator´s levels (protein levels by ELISA) in peri-implant crevicular fluid (PICF) were made. The effect size was estimated and reported as the mean difference. The 95% confidence interval was estimated for each mediator, and the pooled effect was determined significant if two-sided p-values < 0.05 were obtained.
RESULTS
Twenty-two publications were included in the systematic review (qualitative analysis), with nine of these subjected to meta-analyses (quantitative analysis). In the qualitative analysis, higher pro-inflammatory cytokines [Interleukin (IL)-1β, IL-6] and pro-osteoclastogenic mediator [Receptor Activator of Nuclear Factor-Kappa B ligand (RANKL)] levels were observed in PICF of individuals with peri-implant diseases in comparison to healthy individuals. Higher RANKL/osteoprotegerin (OPG) ratios were observed in PICF from individuals with peri-implant diseases in comparison to healthy individuals. Meta-analysis showed higher RANKL levels in diseased groups compared to controls.
CONCLUSIONS
The results showed that the levels of IL-1β, IL-6, IL-10, and RANKL/OPG are not balanced in peri-implant disease, suggesting that these mediators are involved in the host osteo-immunoinflammatory response related to peri-implantitis.
Topics: Humans; Cytokines; Peri-Implantitis; Dental Implants; Interleukin-6; Osteogenesis; Gingival Crevicular Fluid
PubMed: 37355561
DOI: 10.1186/s12903-023-03072-1 -
Nutrients Nov 2022Osteoporosis is caused by the deterioration of bone density and microstructure, resulting in increased fracture risk. It transpires due to an imbalanced skeletal... (Review)
Review
BACKGROUND
Osteoporosis is caused by the deterioration of bone density and microstructure, resulting in increased fracture risk. It transpires due to an imbalanced skeletal remodelling process favouring bone resorption. Various natural compounds can positively influence the skeletal remodelling process, of which naringenin is a candidate. Naringenin is an anti-inflammatory and antioxidant compound found in citrus fruits and grapefruit. This systematic review aims to present an overview of the available evidence on the skeletal protective effects of naringenin.
METHOD
A systematic literature search was conducted using the PubMed and Scopus databases in August 2022. Original research articles using cells, animals, or humans to investigate the bone protective effects of naringenin were included.
RESULTS
Sixteen eligible articles were included in this review. The existing evidence suggested that naringenin enhanced osteoblastogenesis and bone formation through BMP-2/p38MAPK/Runx2/Osx, SDF-1/CXCR4, and PI3K/Akt/-Fos/-Jun/AP-1 signalling pathways. Naringenin also inhibited osteoclastogenesis and bone resorption by inhibiting inflammation and the RANKL pathway.
CONCLUSIONS
Naringenin enhances bone formation while suppressing bone resorption, thus achieving its skeletal protective effects. It could be incorporated into the diet through fruit intake or supplements to prevent bone loss.
Topics: Humans; Animals; Phosphatidylinositol 3-Kinases; Flavanones; Osteogenesis; Bone Resorption
PubMed: 36432535
DOI: 10.3390/nu14224851 -
Association Between Obstructive Sleep Apnea and Osteoporosis: A Systematic Review and Meta-Analysis.International Journal of Endocrinology... Jul 2016Hypoxia reduces osteoblast growth resulting in bone thinning and osteoporosis. Although obstructive sleep apnea (OSA) with recurrent hypoxia might be a contributing... (Review)
Review
CONTEXT
Hypoxia reduces osteoblast growth resulting in bone thinning and osteoporosis. Although obstructive sleep apnea (OSA) with recurrent hypoxia might be a contributing factor for osteoporosis development, whether OSA is a risk or protective factor for osteoporosis has not been demonstrated.
OBJECTIVES
This systematic review and meta-analysis evaluated the association between OSA and osteoporosis using published observational studies.
DATA SOURCES
PubMed/MEDLINE and EMBASE databases.
STUDY SELECTION
We completed a systematic review and meta-analysis of published observational studies that evaluated incidence or prevalence of osteoporosis or bone mineral density in obstructive sleep apnea compared with controls. Severity of OSA was characterized using the apnea-hypopnea index (AHI).
DATA EXTRACTION
Primary outcomes were incidence, prevalence, or odds ratio of having osteoporosis, defined as bone mineral density T-score < -2.5 SD.
RESULTS
Of 353 articles, 344 articles were excluded, 9 underwent full-length review and data were extracted from 7 studies consisting of 113,558 patients. Finally, 3 extracted studies were included in the meta-analysis of osteoporosis. Among cohort studies, the pooled odds ratio of osteoporosis in patients with OSA was 1.92 (95% confidence interval [CI]: 1.24 - 2.97) compared with controls. Among cross-sectional studies, odds of osteoporosis was higher in controls compared with patients with OSA (OR = 0.60, 95% CI: 0.42 - 0.87). In subgroup analysis by gender and study design, in both sexes, only cohort studies had higher odds of osteoporosis compared with controls.
CONCLUSIONS
There was significant association between OSA and osteoporosis in studies with cohort design. Further prospective studies with large numbers of patients adjusted for the effects of age, sex, or BMI are required to comprehensively determine whether OSA is a risk factor for osteoporosis.
PubMed: 27942262
DOI: 10.5812/ijem.36317 -
Frontiers in Genetics 2022Exosomes are nano-extracellular vesicles secreted by a variety of cells. They are composed of a double-layer membrane that can transport a variety of proteins, coding...
Exosomes are nano-extracellular vesicles secreted by a variety of cells. They are composed of a double-layer membrane that can transport a variety of proteins, coding and non-coding genes, and bioactive substances. Exosomes participate in information transmission between cells and regulate processes such as cell proliferation, migration, angiogenesis, and phenotypic transformation. They have broad prospects in the occurrence, development, and treatment of many diseases including orthopedics. Exosomes derived from different types of bone cells such as mesenchymal stem cells, osteoblasts, osteoclasts, and their precursors are recognized to play pivotal roles in bone remodeling processes including osteogenesis, osteoclastogenesis, and angiogenesis. This articlesummarizes the characteristics of exosomes and their research progress in bone remodeling, bone tumors, vascular skeletal muscle injury, spinal cord injury, degenerative disc diseases, cartilage degeneration, osteoarthritis, necrosis of the femoral head, and osteoporosis.
PubMed: 36081990
DOI: 10.3389/fgene.2022.915141 -
Molecules (Basel, Switzerland) Apr 2021Osteoporosis results from excessive bone resorption and reduced bone formation, triggered by sex hormone deficiency, oxidative stress and inflammation. Tanshinones are a...
BACKGROUND
Osteoporosis results from excessive bone resorption and reduced bone formation, triggered by sex hormone deficiency, oxidative stress and inflammation. Tanshinones are a class of lipophilic phenanthrene compounds found in the roots of with antioxidant and anti-inflammatory activities, which contribute to its anti-osteoporosis effects. This systematic review aims to provide an overview of the skeletal beneficial effects of tanshinones.
METHODS
A systematic literature search was conducted in January 2021 using Pubmed, Scopus and Web of Science from the inception of these databases. Original studies reporting the effects of tanshinones on bone through cell cultures, animal models and human clinical trials were considered.
RESULTS
The literature search found 158 unique articles on this topic, but only 20 articles met the inclusion criteria and were included in this review. The available evidence showed that tanshinones promoted osteoblastogenesis and bone formation while reducing osteoclastogenesis and bone resorption.
CONCLUSIONS
Tanshinones modulates bone remodelling by inhibiting osteoclastogenesis and osteoblast apoptosis and stimulating osteoblastogenesis. Therefore, it might complement existing strategies to prevent bone loss.
Topics: Abietanes; Animals; Antioxidants; Humans; Osteoblasts; Osteogenesis
PubMed: 33923673
DOI: 10.3390/molecules26082319 -
Current Genomics Apr 2019Microgravity (μG) negatively influences bone metabolism by affecting normal osteoblast and osteoclast function. μG effects on bone metabolism has been an extensive... (Review)
Review
BACKGROUND
Microgravity (μG) negatively influences bone metabolism by affecting normal osteoblast and osteoclast function. μG effects on bone metabolism has been an extensive field of study in recent years, due to the challenges presented by space flight.
METHODS
We systematically reviewed research data from genomic studies performed in real or simulat-ed μG, on osteoblast and osteoclast cells. Our search yielded 50 studies, of which 39 concerned cells of the osteoblast family and 11 osteoclast precursors.
RESULTS
Osteoblastic cells under μG show a decreased differentiation phenotype, proved by diminished expression levels of Alkaline Phosphatase (ALP) and Osteocalcin (OCN) but no apoptosis. Receptor Activator of NF-κB Ligand (RANKL)/ Osteoprotegerine (OPG) ratio is elevated in favor of RANKL in a time-dependent manner, and further RANKL production is caused by upregulation of Interleukin-6 (IL-6) and the inflammation pathway. Extracellular signals and changes in the gravitational environment are perceived by mechanosensitive proteins of the cytoskeleton and converted to intracellular signals through the Mitogen Activated Protein Kinase pathway (MAPK). This is followed by changes in the ex-pression of nuclear transcription factors of the Activator Protein-1 (AP-1) family and in turn of the NF-κB, thus affecting osteoblast differentiation, cell cycle, proliferation and maturation. Pre-osteoclastic cells show increased expression of the marker proteins such as Tryptophan Regulated Attenuation Protein (TRAP), cathepsin K, Matrix Metalloproteinase-9 (MMP-9) under μG conditions and become sensitized to RANKL.
CONCLUSION
Suppressing the expression of fusion genes such as syncytine-A which acts independently of RANKL, could be possible future therapeutic targets for microgravity side effects.
PubMed: 31929726
DOI: 10.2174/1389202920666190422142053 -
Advances in Clinical and Experimental... May 2024Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and... (Review)
Review
Atherosclerosis is a complex process involving endothelial dysfunction, vascular inflammation, vascular smooth muscle cell (VSMC) proliferation, angiogenesis, and calcification. One of the pathomechanisms of atherosclerosis is the upregulation of Wnt signaling. This study aimed to summarize the current knowledge regarding the role of Wnt signaling and sclerostin in atherosclerosis, vascular calcification, aneurysms, and mortality based on the PubMed database. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendation and identified 160 papers that were included in this systematic review. The published data highlight that the upregulation of Wnt components facilitates the initiation and progression of atherosclerosis, arterial remodeling, VSMCs proliferation and phenotypic transition to the osteoblastic lineage in the arterial wall. This results in protein secretion, cell migration, calcification, fibrosis and aneurysm formation. The transformation of VSMCs into osteoblast-like cells that is observed in atherosclerosis results in sclerostin expression inhibiting the Wnt pathway. Furthermore, it was shown that sclerostin, expressed in atherosclerotic plaques, inhibits aneurysm formation in a mouse model. However, in humans, while the antisclerostin antibody romosozumab inhibits bone resorption, biochemical parameters of endothelial activation and inflammation are not affected, and the incidence of aneurysms is not increased. It was suggested that detecting sclerostin in the calcified aortic atherosclerotic plaques reflects a defense mechanism against Wnt activation and inhibition of atherosclerosis, although this has only been shown in animal models. Moreover, an increased number of vascular cells converted to osteogenic phenotypes results in increased plasma sclerostin concentrations. Therefore, plasma sclerostin derived from bone limits its importance as a global marker of vascular calcification.
Topics: Humans; Vascular Calcification; Atherosclerosis; Animals; Wnt Signaling Pathway; Adaptor Proteins, Signal Transducing; Genetic Markers
PubMed: 37676098
DOI: 10.17219/acem/169567 -
Frontiers in Endocrinology 2023Circulating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation... (Meta-Analysis)
Meta-Analysis
CONTEXT
Circulating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation between adipokines, ghrelin, and bone mineral density (BMD) has been studied over the decades, its correlations are still controversial. Accordingly, an updated meta-analysis with new findings is needed.
OBJECTIVE
This study aimed to explore the impact of serum adipokine and ghrelin levels on BMD and osteoporotic fractures through a meta-analysis.
DATA SOURCES
Studies published till October 2020 in Medline, Embase, and the Cochrane Library were reviewed.
STUDY SELECTION
We included studies that measured at least one serum adipokine level and BMD or fracture risk in healthy individuals. We excluded studies with one or more of the following: patients less than 18 years old, patients with comorbidities, who had undergone metabolic treatment, obese patients, patients with high physical activities, and a study that did not distinguish sex or menopausal status.
DATA EXTRACTION
We extracted the data that include the correlation coefficient between adipokines (leptin, adiponectin, and resistin) and ghrelin and BMD, fracture risk by osteoporotic status from eligible studies.
DATA SYNTHESIS
A meta-analysis of the pooled correlations between adipokines and BMD was performed, demonstrating that the correlation between leptin and BMD was prominent in postmenopausal women. In most cases, adiponectin levels were inversely correlated with BMD. A meta-analysis was conducted by pooling the mean differences in adipokine levels according to the osteoporotic status. In postmenopausal women, significantly lower leptin (SMD = -0.88) and higher adiponectin (SMD = 0.94) levels were seen in the osteoporosis group than in the control group. By predicting fracture risk, higher leptin levels were associated with lower fracture risk (HR = 0.68), whereas higher adiponectin levels were associated with an increased fracture risk in men (HR = 1.94) and incident vertebral fracture in postmenopausal women (HR = 1.18).
CONCLUSIONS
Serum adipokines levels can utilize to predict osteoporotic status and fracture risk of patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021224855, identifier CRD42021224855.
Topics: Male; Humans; Female; Adolescent; Bone Density; Leptin; Adipokines; Adiponectin; Ghrelin; Osteoporotic Fractures
PubMed: 37181034
DOI: 10.3389/fendo.2023.1044039