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Cell Biology International Jun 2024Type 2 diabetic osteoporosis (T2DOP) is a skeletal metabolic syndrome characterized by impaired bone remodeling due to type 2 diabetes mellitus, and there are drawbacks...
Type 2 diabetic osteoporosis (T2DOP) is a skeletal metabolic syndrome characterized by impaired bone remodeling due to type 2 diabetes mellitus, and there are drawbacks in the present treatment. Osteoking (OK) is widely used for treating fractures and femoral head necrosis. However, OK is seldom reported in the field of T2DOP, and its role and mechanism of action need to be elucidated. Consequently, this study investigated whether OK improves bone remodeling and the mechanisms of diabetes-induced injury. We used db/db mice as a T2DOP model and stimulated MC3T3-E1 cells (osteoblast cell line) with high glucose (HG, 50 mM) and advanced glycation end products (AGEs, 100 µg/mL), respectively. The effect of OK on T2DOP was assessed using a combined 3-point mechanical bending test, hematoxylin and eosin staining, and enzyme-linked immunosorbent assay. The effect of OK on enhancing MC3T3-E1 cell differentiation and mineralization under HG and AGEs conditions was assessed by an alkaline phosphatase activity assay and alizarin red S staining. The AGEs/insulin-like growth factor-1(IGF-1)/β-catenin/osteoprotegerin (OPG) pathway-associated protein levels were assayed by western blot analysis and immunohistochemical staining. We found that OK reduced hyperglycemia, attenuated bone damage, repaired bone remodeling, increased tibial and femoral IGF-1, β-catenin, and OPG expression, and decreased receptor activator of nuclear kappa B ligand and receptor activator of nuclear kappa B expression in db/db mice. Moreover, OK promoted the differentiation and mineralization of MC3T3-E1 cells under HG and AGEs conditions, respectively, and regulated the levels of AGEs/IGF-1/β-catenin/OPG pathway-associated proteins. In conclusion, our results suggest that OK may lower blood glucose, alleviate bone damage, and attenuate T2DOP, in part through activation of the AGEs/IGF-1/β-catenin/OPG pathway.
PubMed: 38937979
DOI: 10.1002/cbin.12215 -
Advanced Healthcare Materials Jun 2024Precision material design directed by cell biological processes represents a frontier in developing clinically translatable regenerative technologies. While...
Precision material design directed by cell biological processes represents a frontier in developing clinically translatable regenerative technologies. While understanding cell-material interactions on multipotent progenitor cells yields insights on target tissue differentiation, equally if not more important is the quantification of indirect multicellular interactions. In this work, the relationship of two material properties, phosphate content and stiffness, of a nanoparticulate mineralized collagen glycosaminoglycan scaffold (MC-GAG) in the expression of an endogenous anti-osteoclastogenic secreted protein, osteoprotegerin (OPG) by primary human mesenchymal stem cells (hMSCs) is evaluated. The phosphate content of MC-GAG requires the type III sodium phosphate symporter PiT-1/SLC20A1 for OPG expression, correlating with β-catenin downregulation, but is independent of the effects of phosphate ion on osteogenic differentiation. Using three stiffness MC-GAG variants that do not differ significantly by osteogenic differentiation, it is observed that the softest material elicited ≈1.6-2 times higher OPG expression than the stiffer materials. Knockdown of the mechanosensitive signaling axis of YAP, TAZ, β-catenin and combinations thereof in hMSCs on MC-GAG demonstrates that β-catenin downregulation increases OPG expression by 1.5-fold. Taken together, these data constitute a roadmap for material properties that can used to suppress osteoclast activation via osteoprotegerin expression separately from the anabolic processes of osteogenesis.
PubMed: 38885525
DOI: 10.1002/adhm.202401037 -
PloS One 2024This study aimed to determine the contribution of titanium prepared platelet-rich fibrin (T-PRF) with open flap debridement (OFD) on clinical, biochemical and... (Randomized Controlled Trial)
Randomized Controlled Trial
This study aimed to determine the contribution of titanium prepared platelet-rich fibrin (T-PRF) with open flap debridement (OFD) on clinical, biochemical and radiographic measurements of periodontal regeneration. Twenty periodontitis patients with bilateral intrabony defects and stage III grade A periodontitis were included in the study. A total of 40 defects were randomly selected for OFD alone (control group, n = 20) or combined OFD+ T-PRF (test group, n = 20). Clinical and radiographic parameters (at baseline and nine months after surgery), and growth factor levels in gingival crevicular fluid (at baseline and at two, four, six, and twelve weeks after surgical treatment) were also evaluated. Considering the clinical parameters, alterations in probing pocket depth, gingival marginal level and clinical endpoint in the test regions treated with T-PRF significantly improved (P<0.05). Fibroblast growth factor-2 and platelet-derived growth factor-BB levels between the two groups in the second and fourth weeks were also significantly different (P<0.05). Furthermore, the receptor activator of nuclear factor κB ligand/osteoprotegerin ratio between the groups was significantly different in the second, fourth, sixth, and twelfth weeks (P<0.05). The bone-filling rate was also significantly greater in the test group than in the control group (P <0.001). Compared with OFD alone, combining T-PRF with the procedure was more successful with regards to clinical, radiographic, and biochemical measurements of periodontal regeneration.
Topics: Humans; Platelet-Rich Fibrin; Titanium; Male; Female; Middle Aged; Adult; Alveolar Bone Loss; Gingival Crevicular Fluid; Periodontitis
PubMed: 38843242
DOI: 10.1371/journal.pone.0304970 -
Biomedicines May 2024The global incidence of Type 2 diabetes (T2D) is on the rise, fueled by factors such as obesity, sedentary lifestyles, socio-economic factors, and ethnic backgrounds....
Ethnic Variations in the Levels of Bone Biomarkers (Osteoprostegerin, Receptor Activator of Nuclear Factor Kappa-Β Ligand and Glycoprotein Non-Metastatic Melanoma Protein B) in People with Type 2 Diabetes.
The global incidence of Type 2 diabetes (T2D) is on the rise, fueled by factors such as obesity, sedentary lifestyles, socio-economic factors, and ethnic backgrounds. T2D is a multifaceted condition often associated with various health complications, including adverse effects on bone health. This study aims to assess key biomarkers linked to bone health and remodeling-Osteoprotegerin (OPG), Receptor Activator of Nuclear Factor Kappa-Β Ligand (RANKL), and Glycoprotein Non-Metastatic Melanoma Protein B (GPNMB)-among individuals with diabetes while exploring the impact of ethnicity on these biomarkers. A cross-sectional analysis was conducted on a cohort of 2083 individuals from diverse ethnic backgrounds residing in Kuwait. The results indicate significantly elevated levels of these markers in individuals with T2D compared to non-diabetic counterparts, with OPG at 826.47 (405.8) pg/mL, RANKL at 9.25 (17.3) pg/mL, and GPNMB at 21.44 (7) ng/mL versus 653.75 (231.7) pg/mL, 0.21 (9.94) pg/mL, and 18.65 (5) ng/mL in non-diabetic individuals, respectively. Notably, this elevation was consistent across Arab and Asian populations, except for lower levels of RANKL observed in Arabs with T2D. Furthermore, a positive and significant correlation between OPG and GPNMB was observed regardless of ethnicity or diabetes status, with the strongest correlation (r = 0.473, < 0.001) found among Arab individuals with T2D. Similarly, a positive and significant correlation between GPNMB and RANKL was noted among Asian individuals with T2D (r = 0.401, = 0.001). Interestingly, a significant inverse correlation was detected between OPG and RANKL in non-diabetic Arab individuals. These findings highlight dysregulation in bone remodeling markers among individuals with T2D and emphasize the importance of considering ethnic variations in T2D-related complications. The performance of further studies is warranted to understand the underlying mechanisms and develop interventions based on ethnicity for personalized treatment approaches.
PubMed: 38790981
DOI: 10.3390/biomedicines12051019 -
Molecular Medicine Reports Jul 2024Periodontal disease is a common infectious disease that can lead to the loss of teeth. Hower how to effectively suppress the inflammation with medication is unclear. The...
Periodontal disease is a common infectious disease that can lead to the loss of teeth. Hower how to effectively suppress the inflammation with medication is unclear. The aim of the present study was to investigate the anti‑inflammatory effect of Oroxylin A in periodontitis and its potential role through heme oxygenase‑1 (HO‑1). Primary rat gingival fibroblasts (RGFs) were cultured using the tissue block method and identified by immunofluorescence. Following lipopolysaccharide (LPS) stimulation of RGFs, Oroxylin A was administered at 50, 100, 200 or 400 µg/ml. Reverse transcription‑quantitative PCR was used to assess mRNA expression of cyclooxygenase (COX)‑2, TNF‑α, RANKL and osteoprotegerin (OPG). Western blotting was used to detect protein expression levels of COX ‑2, TNF‑α, RANKL and OPG. Following HO‑1 knockdown, the same treatment was performed. The expression of COX‑2 in rat gingival tissue was observed by immunohistochemistry. One‑way analysis of variance and Student's t test were used for statistical analysis. Oroxylin A downregulated mRNA expression of COX‑2, TNF‑α, RANKL and OPG in LPS‑induced RGFs. With increase of Oroxylin A dose, the expression of HO‑1 was gradually upregulated. When HO‑1 was knocked down, Oroxylin A did not downregulate the expression of COX‑2, TNF‑α, RANKL and OPG in LPS‑induced RGFs. Immunohistochemical results showed that expression of COX‑2 was downregulated by Oroxylin A, and the expression of TNF‑α, RANKL and OPG were also downregulated. Oroxylin A decreased expression of inflammatory cytokines in LPS‑induced RGFs and had a good inhibitory effect on periodontitis in rats.
Topics: Animals; Rats; Flavonoids; Periodontitis; RANK Ligand; Male; Cyclooxygenase 2; Fibroblasts; Osteoprotegerin; Lipopolysaccharides; Gingiva; Tumor Necrosis Factor-alpha; Cytokines; Heme Oxygenase-1; Cells, Cultured; Rats, Sprague-Dawley
PubMed: 38785151
DOI: 10.3892/mmr.2024.13249 -
PeerJ 2024Physical activity is an important factor in modelling the remodelling and metabolism of bone tissue. The aim of the study was to evaluate the changes in indices...
BACKGROUND
Physical activity is an important factor in modelling the remodelling and metabolism of bone tissue. The aim of the study was to evaluate the changes in indices demonstrating bone turnover in men under the influence of maximum-intensity exercise.
METHODS
The study involved 33 men aged 20-25, divided into two groups: experimental ( = 15) and control ( = 18). People training medium- and long-distance running were assigned to the experimental group, and non-training individuals to the control. Selected somatic, physiological and biochemical indices were measured. The level of aerobic fitness was determined using a progressively increasing graded test (treadmill test for subjective fatigue). Blood samples for determinations were taken before the test and 60 minutes after its completion. The concentration of selected bone turnover markers was assessed: bone fraction of alkaline phosphatase (b-ALP), osteoclacin (OC), N-terminal cross-linked telopeptide of the alpha chain of type I collagen (NTx1), N-terminal propeptide of type I progolagen (PINP), osteoprotegerin (OPG). In addition, the concentration of 25(OH)D3 prior to the stress test was determined. Additionally, pre and post exercise, the concentration of lactates in the capillary blood was determined.
RESULTS
When comparing the two groups, significant statistical differences were found for the mean level of: 25(OH)D3 ( = 0.025), b-ALP ( < 0.001), OC ( = 0.004) and PINP ( = 0.029) prior to the test. On the other hand, within individual groups, between the values pre and post the stress test, there were statistically significant differences for the average level of: b-ALP ( < 0.001), NTx1 ( < 0.001), OPG ( = 0.001) and PINP ( = 0.002).
CONCLUSION
A single-session maximum physical effort can become an effective tool to initiate positive changes in bone turnover markers.
Topics: Humans; Male; Adult; Biomarkers; Bone Remodeling; Exercise; Young Adult; Osteoprotegerin; Alkaline Phosphatase; Collagen Type I; Peptides; Running; Exercise Test; Procollagen
PubMed: 38770097
DOI: 10.7717/peerj.17258 -
Journal of Dentistry Jul 2024To perform a comprehensive quantitative and qualitative analysis of the findings from previously published meta-analyses and to assess existing biases. (Review)
Review
OBJECTIVES
To perform a comprehensive quantitative and qualitative analysis of the findings from previously published meta-analyses and to assess existing biases.
DATA/SOURCES
A search was conducted for meta-analyses of observational studies investigating the association between any risk factor and peri‑implantitis in PubMed, Scopus, Cochrane Database of Systematic Reviews, and Epistemonikos, from inception until October 2023 (PROSPERO: CRD42024512408).
STUDY SELECTION
From a total of 5002 publications, 51 full-text articles were evaluated for eligibility, and 12 articles that described 41 unique meta-analyses evaluating the association between risk factors and periimplantitis were selected. Among 41 associations, 24 associations were significant. None of the associations were graded as convincing evidence. Two associations, presence of periodontitis (OR = 3.84 [95 % CI 2.58,5.72]) and cigarette smoking (RR=2.07 [95 % CI 1.41,3.04]) were graded as highly suggestive. Eight associations, diabetes mellitus, hyperglycaemia, lack of prophylaxis, history of chronic periodontal disease, ongoing or history of periodontal disease, implants located in the anterior region of the jaw (maxillary and mandibular), osteoprotegerin (OPG) gene polymorphisms, and lack of keratinized mucosal width were graded as suggestive evidence.
CONCLUSIONS
Periodontitis and cigarette smoking are highly suggestive risk factors for peri‑implantitis. The remaining risk factors which are suggestive require more high-quality studies to be performed to upgrade the level of evidence.
CLINICAL SIGNIFICANCE
The highly suggestive and suggestive risk factors for peri‑implantitis summarized in this umbrella review should be rigorously assessed, monitored and managed by clinicians to reduce the risk peri‑implantitis, as well as to form part of the preoperative consent process.
Topics: Humans; Peri-Implantitis; Risk Factors; Observational Studies as Topic; Meta-Analysis as Topic; Dental Implants; Periodontitis; Bias
PubMed: 38762079
DOI: 10.1016/j.jdent.2024.105065 -
Journal of Clinical Medicine Apr 2024: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor family involved in processes in many inflammatory states. OPG concentration is enhanced in the...
: Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor family involved in processes in many inflammatory states. OPG concentration is enhanced in the majority of chronic kidney disease (CKD) patients and those undergoing renal replacement therapy. The aim of the study was to assess the relation of OPG and chronic inflammation in peritoneal dialysis (PD) patients and to evaluate whether OPG concentrations in plasma and dialysate were related to plasma and dialysate levels of proinflammatory mediators (interleukin 6 (IL-6), high-sensitivity C-reactive protein (hsCRP), interleukin 33 (IL-33) and interleukin 1 receptor-like 1IL-1RL1 (IL-1RL1, sST2)). : The study included 37 patients of the Peritoneal Dialysis Center, Department of Nephrology, Transplantology and Internal Medicine, Szczecin, Poland, 4-6 weeks after the onset of peritoneal dialysis therapy. During a peritoneal equilibration test, plasma (at 2 h) and dialysate (at 4 h) OPG, IL-33, 1IL-1RL1 (sST2), IL-6 and hsCRP concentrations were determined. : Plasma concentration of OPG did not correlate with dialysate OPG level ( = 0.04, = 0.8). There was a strong positive correlation between plasma OPG concentrations and plasma IL-1RL1 (sST2) ( = 0.41; = 0.01), plasma IL-6 ( = 0.38; = 0.01) and plasma hsCRP ( = 0.35; = 0.02). Dialysate OPG concentrations were positively associated with dialysate IL-1RL1 (sST2) ( = 0.37; = 0.02) and dialysate IL-6 levels ( = 0.44; = 0.005). Multivariate analysis showed that higher IL-1RL1 (sST2) ( = +0.38, = 0.006), higher plasma hsCRP ( = +0.32, = 0.02) and older age ( = +0.35, = 0.01) were independent determinants of higher plasma OPG concentration and that higher concentrations of dialysate IL-6 ( = +0.37, = 0.02) were independent determinants of higher dialysate OPG concentration. : Both plasma and dialysate OPG levels are associated with the severity of systemic and local inflammation illustrated by the plasma and dialysate concentrations of IL-1RL1 (sST2), hsCRP and IL-6, suggesting that OPG might have a pivotal role in explaining the milieu of systemic and intraperitoneal inflammation.
PubMed: 38673616
DOI: 10.3390/jcm13082345 -
Biomedicines Apr 2024Osteopontin (OPN) and osteoprotegerin (OPG) are glycoproteins that participate in the regulation of tissue biomineralization. The aim of the project is to verify the...
Osteopontin (OPN) and osteoprotegerin (OPG) are glycoproteins that participate in the regulation of tissue biomineralization. The aim of the project is to verify the hypothesis that the content of OPN and OPG in the aorta walls increases with the development of atherosclerosis and that these proteins are quantitatively related to the main proteins in the extracellular arteries matrix. Quantitative and qualitative analyses of the OPN and OPG content in 101 aorta sections have been conducted. Additionally, an enzyme-linked immunosorbent assay (ELISA) test has been performed to determine the collagen types I-IV and elastin content in the tissues. Correlations between the biochemical data and patients' age/sex, atherosclerosis stages, and calcification occurrences in the tissue have been established. We are the first to report correlations between OPN or OPG and various types of collagen and elastin content (OPG/type I collagen correlation: r = 0.37, = 0.004; OPG/type II collagen: r = 0.34, = 0.007; OPG/type III collagen: r = 0.39, = 0.002, OPG/type IV collagen: r = 0.27, = 0.03; OPG/elastin: r = 0.42, = 0.001; OPN/collagen type I: r = 0.34, = 0.007; OPN/collagen type II: r = 0.52, = 0.000; OPN/elastin: r = 0.61, = 0.001). OPN overexpression accompanies calcium deposit (CA) formation with the protein localized in the calcium deposit, whereas OPG is located outside the CA. Although OPN and OPG seem to play a similar function (inhibiting calcification), these glycoproteins have different tissue localizations and independent expression regulation. The independent expression regulation presumably depends on the factors responsible for stimulating the synthesis of collagens and elastin.
PubMed: 38672202
DOI: 10.3390/biomedicines12040847 -
Antioxidants (Basel, Switzerland) Apr 2024Metabolic syndrome increases the risk of developing diabetes and cardiovascular disease. The regular practice of physical activity is a crucial factor for healthy aging...
Metabolic syndrome increases the risk of developing diabetes and cardiovascular disease. The regular practice of physical activity is a crucial factor for healthy aging and for controlling and preventing chronic diseases. To assess the effects of regular physical activity on the biochemical and inflammatory profiles, as well as the quality of life of older adults diagnosed with metabolic syndrome. Participants (aged 55-70 years; living in the Balearic Islands, Spain) were divided into two groups ( = 50 each) according to the degree of physical activity measured by metabolic equivalents of task (METs). Anthropometric parameters, blood pressure, biochemical and hematological parameters, and inflammatory biomarkers were measured. Beck Depression Inventory and adherence to the Mediterranean diet questionnaires, as well as the Dietary Inflammatory Index, chair test, health-related quality of life (HRQoL), and Rapid Assessment of Physical Activity, were also determined. The characterization of the patients was similar in both groups, showing a homogeneous sample. The group with the highest METs experienced a decrease in depression and an increase in the intensity of physical activity. Adherence to the Mediterranean diet and HRQoL physical dimensions increased in participants with the highest METs, also showing a decrease in glycemia and glycosylated hemoglobin values. Inflammatory biomarkers, including tumor necrosis factor alpha, interleukin-6, interleukin-1β, and osteoprotegerin, decreased in patients practicing more physical activity. High levels of physical activity are related to a healthier lifestyle, characterized by high adherence to the Mediterranean diet, decreased depressive behavior, oxidative stress, and inflammatory status in older people with metabolic syndrome.
PubMed: 38671898
DOI: 10.3390/antiox13040450