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Micro-computed tomography (micro-CT) analysis of the effects of OVX and vitamin C treatment on tibial bone structure: (A) Representative image of tibial longitudinal section, cross section, and space of the tibia trabeculae; (B) trabecular bone mineral density (BMD); (C) cortical BMD; (D–I) quantitative analyses of bone volume per total volume (BV/TV), trabecular thickness (Tb.Th), bone surface area per bone volume (BSA/BV), trabecular separation (Tb.Sp), trabecular number (Tb.N), and cortical wall thickness (Ct.Th) of vitamin C-treated tibias. n = 10 per group. Values represent the mean ± standard deviation. Values with different letters were significantly different according to Duncan’s multiple range test (P < 0.05).
Source publication
This study evaluated the effects of vitamin C on osteogenic differentiation and osteoclast formation, and the effects of vitamin C concentration on bone microstructure in ovariectomized (OVX) Wistar rats. Micro-computed tomography analysis revealed the recovery of bone mineral density and bone separation in OVX rats treated with vitamin C. Histomor...
Citations
... Interestingly, BGP, Dex and Asc, all of them, have the potential to revert the previously mentioned negative feedback loops involving WNT signalling inhibitors, because all of them activate WNT signaling to induce osteogenesis. Dex induces WNT/β-catenin signaling-dependent Runx2 expression at osteogenesis [48]; BGP activates canonical and non-canonical WNT signalling [49], and; Asc activates osteogenesis via Wnt/β-Catenin/ATF4 Signaling Pathways [50]. ...
Background
Recombinant human bone morphogenetic protein 2 (rhBMP-2) and human bone marrow mesenchymal stromal cells (hBM-MSCs) have been thoroughly studied for research and translational bone regeneration purposes. rhBMP-2 induces bone formation in vivo, and hBM-MSCs are its target, bone-forming cells. In this article, we studied how rhBMP-2 drives the multilineage differentiation of hBM-MSCs both in vivo and in vitro.
Methods
rhBMP-2 and hBM-MSCs were tested in an in vivo subcutaneous implantation model to assess their ability to form mature bone and undergo multilineage differentiation. Then, the hBM-MSCs were treated in vitro with rhBMP-2 for short-term or long-term cell-culture periods, alone or in combination with osteogenic, adipogenic or chondrogenic media, aiming to determine the role of rhBMP-2 in these differentiation processes.
Results
The data indicate that hBM-MSCs respond to rhBMP-2 in the short term but fail to differentiate in long-term culture conditions; these cells overexpress the rhBMP-2 target genes DKK1, HEY-1 and SOST osteogenesis inhibitors. However, in combination with other differentiation signals, rhBMP-2 acts as a potentiator of multilineage differentiation, not only of osteogenesis but also of adipogenesis and chondrogenesis, both in vitro and in vivo.
Conclusions
Altogether, our data indicate that rhBMP-2 alone is unable to induce in vitro osteogenic terminal differentiation of hBM-MSCs, but synergizes with other signals to potentiate multiple differentiation phenotypes. Therefore, rhBMP-2 triggers on hBM-MSCs different specific phenotype differentiation depending on the signalling environment.
... Vitamin C has been found to help in reducing inflammation and chronic inflammatory disease complications [123]. It modulates osteoblastogenesis and osteoclastogenesis through Nrf2 activation and thereby promotes bone formation, remodeling and healing [124,125]. It can be used to improve healing after oral surgery and to prevent the incidence and development of periodontal disease [126][127][128]. ...
Based on the evidence of a significant communication and connection pathway between the bone and immune systems, a new science has emerged: osteoimmunology. Indeed, the immune system has a considerable impact on bone health and diseases, as well as on bone formation during grafts and its stability over time. Chronic inflammation induces the excessive production of oxidants. An imbalance between the levels of oxidants and antioxidants is called oxidative stress. This physio-pathological state causes both molecular and cellular damage, which leads to DNA alterations, genetic mutations and cell apoptosis, and thus, impaired immunity followed by delayed or compromised wound healing. Oxidative stress levels experienced by the body affect bone regeneration and maintenance around teeth and dental implants. As the immune system and bone remodeling are interconnected, bone loss is a consequence of immune dysregulation. Therefore, oral tissue deficiencies such as periodontitis and peri-implantitis should be regarded as immune diseases. Bone management strategies should include both biological and surgical solutions. These protocols tend to improve immunity through antioxidant production to enhance bone formation and prevent bone loss. This narrative review aims to highlight the relationship between inflammation, oxidation, immunity and bone health in the oral cavity. It intends to help clinicians to detect high-risk situations in oral surgery and to propose biological and clinical solutions that will enhance patients’ immune responses and surgical treatment outcomes.
... The same group has shown that Vitamin C prevents bone resorption by osteoclasts in an inflammatory environment, indicating the reasonable efficiency of vitamin C supplementation as a therapeutic intervention in postmenopausal osteoporosis and bone loss associated with chronic inflammatory conditions. Vitamin C deficiency is also associated with increased expression of tumour necrosis factor ligand superfamily member 11 (RANKL), which acts as a critical inducer of osteoclasts and bone resorption but also as an inflammatory mediator (Brzezińska et al., 2020;Choi et al., 2019). ...
The process of bone repair after trauma or fracture will involve cells, signalling molecules, and processes that have been active during the remodelling process. The new study found that Aloin can promote the expression of osteogenic differentiation regulators, such as Bmp-1 (Bone morphogenetic protein 1) and Runx1 (Runt-related transcription factor 1) in MC3T3–E1 cells, where Runx1 is a transcription factor in osteogenic differentiation—knowing and analyzing aloin extract on the histopathological picture of osteogenesis in Wistar strain rattus norvegicus fractures. This type of research is a laboratory experimental test with a post-test-only control group design. The population number will be divided into four groups, namely positive control group (+), negative control (-), treatment group 1, and treatment group 1, with 14 samples using the Purposive Sampling technique. Univariate data analysis is presented as mean and standard deviation and one-way ANOVA statistical test. Data processing using computerized IBM version 15.0 of the SPSS program. Histopathological picture of osteogenesis in fractures of male rats (Rattus norvegicus) based on osteoblast values at least at K(-), which is 30.64, and K(+), which is 31.90. In the P1 group, the highest average osteoblast value was 39.58, and P1's was 38.14. The osteoclast value is obtained at least at K(-) and 8, and K(+) is 19.01. In the P1 group, the highest average osteoclast value was 16.73, and P1 was 11.70. Aloin extract did not affect the histopathological picture of osteogenesis in fractures of male rats (Rattus norvegicus) with a sig of >0.05.
... Research indicates that vitamin C can enhance the production of genes influencing osteogenesis. For instance, it increases genes like bone morphogenetic protein-2, Runt-related transcription factor 2, and osteocalcin, while decreasing the production of bone-destructive genes such as cathepsin K, tartrate-resistant acid phosphatase, receptor activator of nuclear factor kappa-B, and receptor activator of nuclear factor kappa-B ligand [39]. Considering the positive impact of vitamin C on bone healing, an in vitro study utilizing a combination of electrospinning and freeze-drying techniques demonstrated the preparation of highly porous 3D scaffolds comprising different concentrations of vitamin C in poly(lactic acid)/poly(caprolactone)/gelatin (PLA/PCL/Gel). ...
Vitamin C, an essential water-soluble vitamin, is known for its pivotal role in various biological functions. This chapter provides an overview of vitamin C, focusing on its chemical structure and synthesis, its multifaceted biological functions within the body, and its remarkable role as a powerful antioxidant. The significance of vitamin C in maintaining immune function, its contributions to collagen synthesis, and its involvement in cognitive health are explored. Moreover, the dual nature of vitamin C as both a pro-oxidant and an antioxidant is highlighted, emphasizing its broad impact on health and well-being. This comprehensive examination of vitamin C underscores its critical role in safeguarding against oxidative damage-related diseases and supporting overall health.
... A low protein state may lead to a low ALP activity (51,52) but again this observation is not consistent in kwashiorkor (53). Vitamins C and B12 have been shown to promote bone growth, and deficiencies have a negative impact on bone growth (54) and increase the rate of osteoporosis (55). ALP is a marker for bone turnover therefore any decrease in turnover will affect the activity of ALP (55). ...
... Vitamin C seems to modulate the maturation of osteoblasts (bone-forming cells) and osteoclasts (large multinucleated cells taking part in bone resorption) [12, 81,83,84]. Of interest, a pioneer study showed that vitamin C activates osteoblastogenesis and inhibits osteoclastogenesis via Wnt/β-catenin/ATF4 signaling pathways in ovariectomized Wistar rats─an osteoprotective effect of vitamin C [85]. ...
Pathophysiology may be defined as a hybrid fundamental science, focusing on changes in the body's major functions during diseases, such as scurvy and other nutritional deficiencies. Mostly, it allows to understand the biological modifications triggering the illness-related manifestations. Thus, the aim of this study is to critically review the pathophysiological and clinical alterations of this metabolic disorder under various age groups (i.e., children, adults, and the elderly). Other vulnerable populations are revised too, for instance, individuals with malnutrition and (or) alcoholism, and diabetes mellitus. Nevertheless, the present work does not discuss in detail the mandatory vitamin C supplementation in scurvy.
... Estimula la actividad de la fosfatasa alcalina y es necesaria para la formación de matriz de colágeno tipo I en tejidos animales y humanos, así como para la expresión de marcadores osteoblásticos y mineralización 5 . Se ha demostrado que la adición de vitamina C a las células cultivadas similares a las de los osteoblastos estimula el depósito inicial de una matriz extracelular de colágeno, seguida de la inducción de genes específicos asociados con el fenotipo de osteoblastos, como la fosfatasa alcalina y osteocalcina 6 . Además, en las líneas celulares pre-osteoblásticas y osteoblásticas promueve la colagenogénesis y actúa a través del factor de crecimiento transformador beta para estimular la diferenciación de los osteoblastos y la neoformación ósea 4,7 . ...
Objective: To compare, through biomechanical torque tests and resonance frequency analysis, Oxalife surface titanium
implants, without and with vitamin C, placed in rabbit femurs. Methods: 17 Tree-Oss Rapid surface Oxalife implants of 7 mm
in length and 3.3 mm in diameter with external hexagon connection were used, placed in the femur of 8 hybrid breed rabbits.
Following the drilling sequence indicated by the manufacturer. Insertion torque and resonance frequency analysis were
recorded to measure the initial stability coefficient. Euthanasia was performed at 60 days; then the implants were exposed to
measure the final or biological stability coefficient through resonance frequency analysis (Osstell) and removal torque (Mark-
10 Gauge). The data were subjected to parametric contrast Student test. Results in Ncm: Mean insertion torque value for the
experimental group 16.5 ± 3.7 and for the control group 23.3 ± 4.2, with a significant difference (p<0.01). Mean removal torque
for the experimental group 69.3 ± 17.4, and control group 87.2 ± 24.9 without significant differences (p=0.14). Average initial
ISQ for the experimental group 40.2 ± 7.8 and for the control group 44.7 ± 6.9 (p=0.24). Final ISQ average for the experimental
group 50.8 ± 1.1 and for the control 50.5 ± 2.0 (p=0.77) without differences in both measurements. Conclusion: The addition
of vitamin C on t
... In a separate study using mesenchymal stromal cells of bone marrow, supplementation of ascorbic acid enhanced proliferation of mesenchymal stromal cells without compromising the differentiation potency [50]. Conductor to these observations, induction by ascorbic acid improve proliferation of suspension MNCs, and this effect marked the beginning of a differentiation process induced by ascorbic acid [51], in addition the combination of ascorbic acid with collagen which has reported its beneficial effect on enhancing bone formation [52], collagen-based scaffolds can be surface modified by attaching bioactive substances to promote bone regeneration. Collagen based hydrogel is made up of collagen and other materials, which makes up for the problem of excessive collagen degradation and swelling. ...
Dental implants inserted into the jawbone, where they fuse to provide a stable, durable foundation for restorations. However, even the best dental implants can fail. Therefore, researchers focus on developing surface coatings for implants to enhance Osseointegration. Objectives of this study are to form a biodegradable scaffold by electrospinning of ascorbic acid, collagen, and polycaprolactone (PCL) fibers onto the surface of commercial pure titanium (CpTi) implants. Methods three composite fibers (scaffold) created using the electrospinning procedure first scaffold formed from collagen/PCL, the second scaffold formed from ascorbic acid added to the collagen/PCL, and finally the third scaffold formed from PCL polymer alone with ascorbic acid. After that characterization done by SEM, AFM , scaffolds cross cut test, and wettability. Another part of study include examination of histological response for coated and uncoated implant in femur of rabbits statistical analysis of data was performed by SPSS version 22. The results of SEM analysis revealed the formation of nanofiber scaffold with pores. while the results of AFM surface roughness indicate that the ascorbic acid/PCL scaffold had the roughest surface compared to the other two groups .And the collagen /PCL scaffold appears to have a rather smooth topography,. Histological finding after 2 and 6 week of implantation appear show thicker layer of fibrous osteogenic cells in ascorbic acid loaded to collagen/PCL coat on CpTi. The cross-cut test demonstrates that scaffold adhesion to CpTi is robust and strong. within limitation of this study it can be concluded that Ascorbic acid with collagen can be efficiently coat titanium surface by using electrospinning technique. In addition, a scaffold formed with an appropriate properties include improve hydrophicity of surface and increase surface roughness in addition to increase shear bond between implant and bone.
... It facilitates neutrophil clearance during the inflammatory phase and supports collagen synthesis and maturation during the proliferative phase [31,32]. Notably, AA simultaneously increases the expression of genes related to osteogenesis (such as bone morphogenetic protein-2, osteocalcin, and RUNX2) and reduces the expression of those related to osteoclast differentiation (such as tartrate-resistant acid phosphatase, cathepsin K, receptor activator of nuclear factor kappa-B, and receptor activator of nuclear factor kappa-B ligand) [33]. Additionally, it upregulates endogenous retroviruses in lymphoma cells, inducing the viral defense pathway to activate the immune system and recognize tumor cells, thereby triggering interferon response [34]. ...
... The role of vitamin C in bone metabolism is notable as it is associated with the hydroxylation of collagen and the expression of non-collagenous proteins, such as alkaline phosphatase, osteonectin, and osteocalcin. Vitamin C also promotes the expression of genes related to osteoblastogenesis and osteoclastogenesis via the Wnt/βcatenin/ATF4 signaling pathways (7)(8)(9). Preclinical and clinical studies have shown that vitamin C deficiency inhibits collagen synthesis and decreases bone formation. In vivo and in vitro studies have shown that vitamin C deficiency stimulates osteoclastogenesis by upregulating the RANKL/RANK pathway, and inhibits osteoblastogenesis by decreasing pro-collagen I mRNA expression and hydroxylation of collagen fibers (7-11) Thus, this deficiency has been a critical risk factor in osteoporotic fractures (11,12). ...
... Oxidative stress is an imbalance between the production of oxidant and antioxidant species, with the disruption of redox signaling and/or molecular damage caused by overproduction of reactive oxygen species (ROS) (24). Animal experiments and clinical studies have shown that excessive activation of inflammatory cells produces a large number of ROS, leading to acute oxidative stress at fracture sites (8,23). Vitamin C, as an antioxidant, participates in redox reactions to neutralize ROS and alleviate oxidative stress, which inevitably leads to the excessive consumption of vitamin C (23, 25). ...
Introduction
The role of vitamin C in pediatric fractures has not received much attention, although it is known to be a factor in osteoporotic fractures in the elderly. This case-control study aimed to investigate the changes in serum vitamin C levels among children with limb fractures.
Methods
We recruited 325 children with and 316 children without limb fractures hospitalized between January 2021 and December 2021. Following admission, basic demographic data of all participants were collected, and fasting serum vitamin C levels were determined using ultra-high-performance liquid chromatography-tandem mass spectrometry.
Results
The mean age of the fracture group was 5.1 years (95% CI, 4.83–5.33). The serum vitamin C levels in the fracture group (4.48 µg/ml) were significantly lower than those in the control group (8.38 µg/ml) (p < 0.0001). Further subgroup analysis of the fracture group revealed that serum vitamin C levels decreased significantly after 4 years of age and there was a significant difference in the duration after injury between <6 and >6 h (p = 0.0224). Spearman’s rank correlation coefficient suggested that age and vitamin C levels were negatively correlated in the fracture group.
Conclusion
In general, children with limb fractures had lower serum vitamin C levels, especially those aged 4 years and over.
