Jaboticaba Peel Extract Attenuates Ovariectomy-Induced Bone Loss by Preserving Osteoblast Activity.

Therapies to prevent osteoporosis are relevant since it is one of the most common non-communicable human diseases in the world and the most prevalent bone disorder in adults. Since jaboticaba peel extract (JPE) added to the culture medium enhanced the osteogenic potential of mesenchymal stem cells (MSCs) derived from osteoporotic rats, we hypothesized that JPE prevents the development of ovariectomy-induced osteoporosis. Ovariectomized rats were treated with either JPE (30 mg/kg of body weight) or its vehicle for 90 days, starting 7 days after the ovariectomy. Then, the femurs were subjected to microcomputed tomography and histological analyses, and the osteoblast and adipocyte differentiation of MSCs was evaluated. JPE attenuated ovariectomy-induced bone loss, as evidenced by higher bone volume/total volume and trabecular number, along with lower trabecular separation and bone marrow adiposity. These protective effects of JPE on bone tissue are due to its ability to prevent the imbalance between osteoblast and adipocyte differentiation of MSCs, since, compared with MSCs derived from ovariectomized rats treated with vehicle, MSCs treated with JPE exhibited higher gene and protein expression of osteogenic markers and extracellular matrix mineralization, as well as lower gene expression of adipogenic markers. These data highlight the potential therapeutic use of JPE to prevent osteoporosis.

Green Foaming of Biologically Extracted Chitin Hydrogels Using Supercritical Carbon Dioxide for Scaffolding of Human Osteoblasts.

Chitin is a structural polysaccharide abundant in the biosphere. Chitin possesses a highly ordered crystalline structure that makes its processing a challenge. In this study, chitin hydrogels and methanogels, prepared by dissolution in calcium chloride/methanol, were subjected to supercritical carbon dioxide (scCO2) to produce porous materials for use as scaffolds for osteoblasts. The control of the morphology, porosity, and physicochemical properties of the produced materials was performed according to the operational conditions, as well as the co-solvent addition. The dissolution of CO2 in methanol co-solvent improved the sorption of the compressed fluid into the hydrogel, rendering highly porous chitin scaffolds. The chitin crystallinity index significantly decreased after processing the hydrogel in supercritical conditions, with a significant effect on its swelling capacity. The use of scCO2 with methanol co-solvent resulted in chitin scaffolds with characteristics adequate to the adhesion and proliferation of osteoblasts.

Vascular smooth muscle cells exhibit elevated hypoxia-inducible Factor-1α expression in human blood vessel organoids, influencing osteogenic performance.

Considering the importance of alternative methodologies to animal experimentation, we propose an organoid-based biological model for in vitro blood vessel generation, achieved through co-culturing endothelial and vascular smooth muscle cells (VSMCs). Initially, the organoids underwent comprehensive characterization, revealing VSMCs (α-SMA + cells) at the periphery and endothelial cells (CD31+ cells) at the core. Additionally, ephrin B2 and ephrin B4, genes implicated in arterial and venous formation respectively, were used to validate the obtained organoid. Moreover, the data indicates exclusive HIF-1α expression in VSMCs, identified through various methodologies. Subsequently, we tested the hypothesis that the generated blood vessels have the capacity to modulate the osteogenic phenotype, demonstrating the ability of HIF-1α to promote osteogenic signals, primarily by influencing Runx2 expression. Overall, this study underscores that the methodology employed to create blood vessel organoids establishes an experimental framework capable of producing a 3D culture model of both venous and arterial endothelial tissues. This model effectively guides morphogenesis from mesenchymal stem cells through paracrine signaling, ultimately leading to an osteogenic acquisition phenotype, with the dynamic involvement of HIF-1α.

Increased Osteoblastic and Osteocytic in Vitro Cell Viability by Yerba Mate (Ilex paraguariensis).

BACKGROUND: Yerba mate (YM, Ilex paraguariensis) consumption beneficially affects the bones. However, whether YM components exert their effect on bone cells directly remains elusive. METHODS: We evaluated how main YM components affect osteoblastic (MC3T3-E1) and osteocytic (MLO-Y4) cells in vitro when administered separately or in an aqueous extract. MC3T3-E1 and MLO-Y4 cells were exposed to three different experimental conditions: (1) Caffeine, chlorogenic acid, and their combinations; (2) Caffeine, rutin, and their combinations; (3) Aqueous YM extract. RESULTS: All polyphenol and caffeine concentrations as well as that of their tested combinations significantly increased MC3T3-E1 cell viability from 16.6% to 34.8% compared to the control. In MLO-Y4 cells, the lowest rutin and the two highest caffeine concentrations significantly increased cell viability by 11.9, 14.9, and 13.7%, respectively. While rutin and caffeine combinations tended to increase MLO-Y4 cell viability, different chlorogenic acid and caffeine combinations did not affect it. Finally, the aqueous YM extract significantly increased MLO-Y4, MC3T3-E1, and differentiated MC3T3-E1 cell viability compared to the control without treatment. CONCLUSIONS: YM components (rutin, chlorogenic acid, and caffeine) positively affected bone cells, mainly pre-osteoblast cells. Moreover, the aqueous YM extract significantly increased MLO-Y4, MC3T3-E1, and differentiated MC3T3-E1 cell viabilities indicating an additional relevant nutritional property of YM infusion. Further studies would be required to elucidate the underlying effector mechanism of YM on the bones and its relationship with previously described in vivo positive effects.

L-PRF Secretome from Both Smokers/Nonsmokers Stimulates Angiogenesis and Osteoblast Differentiation In Vitro.

Leukocyte and Platelet-Rich Fibrin (L-PRF) is part of the second generation of platelet-concentrates. L-PRF derived from nonsmokers has been used in surgical procedures, with its beneficial effects in wound healing being proven to stimulate biological activities such as cell proliferation, angiogenesis, and differentiation. Cigarette smoking exerts detrimental effects on tissue healing and is associated with post-surgical complications; however, evidence about the biological effects of L-PRF derived from smokers is limited. This study evaluated the impact of L-PRF secretome (LPRFS) derived from smokers and nonsmokers on angiogenesis and osteoblast differentiation. LPRFS was obtained by submerging L-PRF membranes derived from smokers or nonsmokers in culture media and was used to treat endothelial cells (HUVEC) or SaOs-2 cells. Angiogenesis was evaluated by tubule formation assay, while osteoblast differentiation was observed by alkaline phosphatase and osterix protein levels, as well as in vitro mineralization. LPRFS treatments increased angiogenesis, alkaline phosphatase, and osterix levels. Treatment with 50% of LPRFS derived from smokers and nonsmokers in the presence of osteogenic factors stimulates in vitro mineralization significantly. Nevertheless, differences between LPRFS derived from smokers and nonsmokers were not found. Both LPRFS stimulated angiogenesis and osteoblast differentiation in vitro; however, clinical studies are required to determine the beneficial effect of LPRFS in smokers.

Polysacharide of Agaricus blazei gel mitigates bone necrosis in model of the jaws related to bisphosphonate via Wnt signaling.

To investigate de effect of PAb gel on the bone tissue of rats submitted to Bisphosphonate-related osteonecrosis of the jaws (BRONJ). Initially, 54 animals were submitted to BRONJ model by Zoledronic Acid (ZA) (0.1 mg/kg 3x/wk for 9 wk, ip), followed by the 1st upper left molar extraction at the 8th wk. After tooth removal, the animals were divided into 3 groups, ZA that received placebo gel or PAb gel that received 1% PAb gel, inside the dental alveolus. The control Group (CONTROL) received 0.1 mg/kg of 0.9% saline and then placebo gel. Three weeks after tooth extraction, the animals were euthanized, and maxillae were colleted for macroscopic, radiographic, histological and Raman spectomery assays. Additionally, GSK3b, beta-catenin, and Runx2 mRNA expressions were determined. Blood samples were collected for the analysis of Bone-specific alkaline phosphatase (BALP) levels. PAb gel improved mucosal healing, increased the number of viable osteocytes, while it reduced the number of empty lacunae, as well as the amount of bone sequestration. Furthermore, PAb gel positively influenced the number and functionality of osteoblasts by stimulating Wnt signaling, thereby inducing bone remodeling. Additionally, PAb gel contributed to improved bone quality, as evidenced by an increase in bone mineral content, a decrease in bone solubility, and an enhancement in the quality of collagen, particularly type I collagen. PAb gel mitigated bone necrosis by stimulating of bone remodeling through Wnt signaling and concurrently improved bone quality. PAb gel emerges as a promising pharmacological tool for aiding in BRONJ therapy or potentially preventing the development of BRONJ.

BMP7-induced osteoblast differentiation requires hedgehog signaling and involves nuclear mechanisms of gene expression control.

During the morphological changes occurring in osteoblast differentiation, Sonic hedgehog (Shh) plays a crucial role. While some progress has been made in understanding this process, the epigenetic mechanisms governing the expression of Hh signaling members in response to bone morphogenetic protein 7 (BMP7) signaling in osteoblasts remain poorly understood. To delve deeper into this issue, we treated pre-osteoblasts (pObs) with 100 ng/mL of BMP7 for up to 21 days. Initially, we validated the osteogenic phenotype by confirming elevated expression of well-defined gene biomarkers, including Runx2, Osterix, Alkaline Phosphatase (Alp), and bone sialoprotein (Bsp). Simultaneously, Hh signaling-related members Sonic (Shh), Indian (Ihh), and Desert (Dhh) Hedgehog (Hh) exhibited nuanced modulation over the 21 days in vitro period. Subsequently, we evaluated epigenetic markers, and our data revealed a notable change in the CpG methylation profile, considering the methylation/hydroxymethylation ratio. CpG methylation is a reversible process regulated by DNA methyltransferases and demethylases, including Ten-eleven translocation (Tets), which also exhibited changes during the acquisition of the osteogenic phenotype. Specifically, we measured the methylation pattern of Shh-related genes and demonstrated a positive Pearson correlation for GLI Family Zinc Finger 1 (Gli1) and Patched (Ptch1). This data underscores the significance of the epigenetic machinery in modulating the BMP7-induced osteogenic phenotype by influencing the activity of Shh-related genes. In conclusion, this study highlights the positive impact of epigenetic control on the expression of genes related to hedgehog signaling during the morphogenetic changes induced by BMP7 signaling in osteoblasts.

Osteoblastic differentiation and changes in the redox state in pulp stem cells by laser treatment.

The aim of this study was to determine the effect of low-level laser therapy (LLLT) on cell proliferation, mitochondrial membrane potential changes (∆Ψm), reactive oxygen species (ROS), and osteoblast differentiation of human dental pulp stem cells (hDPSCs). These cells were irradiated with 660- and 940-nm lasers for 5 s, 50 s, and 180 s. Cell proliferation was assessed using the resazurin assay, cell differentiation by RUNX2 and BMP2 expression, and the presence of calcification nodules using alizarin-red S staining. ROS was determined by the dichlorofluorescein-diacetate technique and changes in ∆Ψm by the tetramethylrhodamine-ester assay. Data were analyzed by a Student's t-test and Mann-Whitney U test. The 940-nm wavelength for 5 and 50 s increased proliferation at 4 days postirradiation. After 8 days, a significant decrease in proliferation was observed in all groups. Calcification nodules were evident in all groups, with a greater staining intensity in cells treated with a 940-nm laser for 50 s, an effect that correlated with increased RUNX2 and BMP2 expression. ROS production and Δψm increased independently of irradiation time. In conclusion, photobiomodulation (PBM) with LLLT induced morphological changes and reduced cell proliferation rate, which was associated with osteoblastic differentiation and increased ROS and Δψm, independent of wavelength and time.

Combination of in silico and cell culture strategies to predict biomaterial performance: Effects of sintering temperature on the biological properties of hydroxyapatite.

Advances in methodologies to evaluate biomaterials brought an explosive growth of data, ensuing computational challenges to better analyzing them and allowing for high-throughput profiling of biological systems cost-efficiently. In this sense, we have applied bioinformatics tools to better understand the biological effect of different sintering temperatures of hydroxyapatite (abbreviated HA; at 1100, 1150, and 1250°C) on osteoblast performance. To do, we have better analyzed an earlier deposited study, in which the access code is E-MTAB-7219, which the authors have explored different in silico tools on this purpose. In this study, differential gene expression analyses were performed using the gene set variation analysis (GSVA) algorithm from the transcriptomes respecting the thermal changes of HA, which were validated using exclusively in vitro strategies. Furthermore, in silico approaches elected biomarkers during cell behavior in response to different sintering temperatures of HA, and it was further validated using cell culture and qPCR technologies. Altogether, the combination of those strategies shows the capacity of sintered HA at 1250°C to present a better performance in organizing an adequate microenvironment favoring bone regeneration, angiogenesis and material resorption stimulus once it has promoted higher involvement of genes such as CDK2, CDK4 (biomarkers of cell proliferation), p15, Osterix gene (related with osteogenic differentiation), RANKL (related with osteoclastogenesis), VEGF gene (related with angiogenesis), and HIF1α (related with hypoxia microenvironment). Altogether, the combination of in silico and cell culture strategies shows the capacity of sintered HA at 1250°C in guaranteeing osteoblast differentiation and it can be related in organizing an adequate microenvironment favoring bone regeneration, angiogenesis, and material resorption stimulus.

Red light-emitting diode therapy minimizes the functional deleterious effects of the antiretroviral ritonavir on osteoblasts in vitro.

PURPOSE: Long-term human immunodeficiency virus (HIV)-infected patients are considered at higher risk for osteoporosis. Among the various causes that lead these patients to lower bone health, there is the use of antiretroviral drugs (ARVs), especially protease inhibitors (PI), such as ritonavir (RTV). In this context, emerge the potential benefits of LED therapy, whose effects on bone cells are currently being extensively studied, showing a modulation in cell differentiation. However, it remains unclear if photobiostimulation might interfere with RTV effects on osteoblast differentiation. METHODS: In the present study, we investigated the effects of red LED (625 nm) irradiation (15 mW/cm2, 0.2 J/cm2, and 8 mW/cm2, 0.12 J/cm2) on osteoblast cell line MC3T3-E1 treated with RTV (2.5, 5, and 10 µg/mL). RESULTS: Our results indicated that red LED irradiation was able to reverse, or at least minimize, the deleterious effects of RTV on the osteoblasts. Neither the ARV treatments 5 and 10 µg/mL (104.4% and 95.01%) nor the LED protocols (100.3% and 105.7%) statistically altered cell viability, assessed by the MTT assay. Also, the alkaline phosphatase activity and mineralization showed a decrease in osteoblast activity followed by ARV exposure (39.3-73%), which was attenuated by LED in more than 70% with statistical significance (p < 0.05). CONCLUSION: In conclusion, photobiostimulation with red LED at 625 nm was associated with improved beneficial biological effects as a potential inducer of osteogenic activity on RTV-affected cells. This is the first study that investigated the benefits of red LED irradiation over ARV-treated in vitro osteoblasts.

Fibroblasts inhibit osteogenesis by regulating nuclear-cytoplasmic shuttling of YAP in mesenchymal stem cells and secreting DKK1.

BACKGROUND: Fibrous scars frequently form at the sites of bone nonunion when attempts to repair bone fractures have failed. However, the detailed mechanism by which fibroblasts, which are the main components of fibrous scars, impede osteogenesis remains largely unknown. RESULTS: In this study, we found that fibroblasts compete with osteogenesis in both human bone nonunion tissues and BMP2-induced ectopic osteogenesis in a mouse model. Fibroblasts could inhibit the osteoblastic differentiation of mesenchymal stem cells (MSCs) via direct and indirect cell competition. During this process, fibroblasts modulated the nuclear-cytoplasmic shuttling of YAP in MSCs. Knocking down YAP could inhibit osteoblast differentiation of MSCs, while overexpression of nuclear-localized YAP-5SA could reverse the inhibition of osteoblast differentiation of MSCs caused by fibroblasts. Furthermore, fibroblasts secreted DKK1, which further inhibited the formation of calcium nodules during the late stage of osteogenesis but did not affect the early stage of osteogenesis. Thus, fibroblasts could inhibit osteogenesis by regulating YAP localization in MSCs and secreting DKK1. CONCLUSIONS: Our research revealed that fibroblasts could modulate the nuclear-cytoplasmic shuttling of YAP in MSCs, thereby inhibiting their osteoblast differentiation. Fibroblasts could also secrete DKK1, which inhibited calcium nodule formation at the late stage of osteogenesis.

Mechanosignaling-related angiocrine factors drive osteoblastic phenotype in response to zirconia.

BACKGROUND: The growing use of zirconia as a ceramic material in dentistry is attributed to its biocompatibility, mechanical properties, esthetic appearance, and reduced bacterial adhesion. These favorable properties make ceramic materials a viable alternative to commonly used titanium alloys. Mimicking the physiological properties of blood flow, particularly the mechanosignaling in endothelial cells (ECs), is crucial for enhancing our understanding of their role in the response to zirconia exposure. METHODS: In this study, EC cultures were subjected to shear stress while being exposed to zirconia for up to 3 days. The conditioned medium obtained from these cultures was then used to expose osteoblasts for a duration of 7 days. To investigate the effects of zirconia on osteoblasts, we examined the expression of genes associated with osteoblast differentiation, including Runx2, Osterix, bone sialoprotein, and osteocalcin genes. Additionally, we assessed the impact of mechanosignaling-related angiocrine factors on extracellular matrix (ECM) remodeling by measuring the activities of matrix metalloproteinases 2 and 9 (MMP2 and MMP9) during the acquisition of the osteogenic phenotype, which precedes mineralization. RESULTS: Our data revealed that mechanosignaling-related angiocrine factors play a crucial role in promoting an osteoblastic phenotype in response to zirconia exposure. Specifically, exposed osteoblasts exhibited significantly higher expression levels of genes associated with osteoblast differentiation, such as Runx2, Osterix, bone sialoprotein, and osteocalcin genes. Furthermore, the activities of MMP2 and MMP9, which are involved in ECM remodeling, were modulated by mechanosignaling-related angiocrine factors. This modulation is likely an initial event preceding the mineralization phase. CONCLUSION: Based on our findings, we propose that mechanosignaling drives the release of angiocrine factors capable of modulating the osteogenic phenotype at the biointerface with zirconia. This process creates a microenvironment that promotes wound healing and osseointegration. Moreover, these results highlight the importance of considering the mechanosignaling of endothelial cells in the modulation of bone healing and osseointegration in the context of blood vessel effects. Our data provide new insights and open avenues for further investigation into the influence of mechanosignaling on bone healing and the osseointegration of dental devices.

Fibroblasts inhibit osteogenesis by regulating nuclear-cytoplasmic shuttling of YAP in mesenchymal stem cells and secreting DKK1

BACKGROUND: Fibrous scars frequently form at the sites of bone nonunion when attempts to repair bone fractures have failed. However, the detailed mechanism by which fibroblasts, which are the main components of fibrous scars, impede osteogenesis remains largely unknown. RESULTS: In this study, we found that fibroblasts compete with osteogenesis in both human bone nonunion tissues and BMP2-induced ectopic osteogenesis in a mouse model. Fibroblasts could inhibit the osteoblastic differentiation of mesenchymal stem cells (MSCs) via direct and indirect cell competition. During this process, fibroblasts modulated the nuclear-cytoplasmic shuttling of YAP in MSCs. Knocking down YAP could inhibit osteoblast differentiation of MSCs, while overexpression of nuclear-localized YAP-5SA could reverse the inhibition of osteoblast differentiation of MSCs caused by fibroblasts. Furthermore, fibroblasts secreted DKK1, which further inhibited the formation of calcium nodules during the late stage of osteogenesis but did not affect the early stage of osteogenesis. Thus, fibroblasts could inhibit osteogenesis by regulating YAP localization in MSCs and secreting DKK1. CONCLUSIONS: Our research revealed that fibroblasts could modulate the nuclear-cytoplasmic shuttling of YAP in MSCs, thereby inhibiting their osteoblast differentiation. Fibroblasts could also secrete DKK1, which inhibited calcium nodule formation at the late stage of osteogenesis.

Improvement of osteoblast adhesion, viability, and mineralization by restoring the cell cytoskeleton after bisphosphonate discontinuation in vitro

Abstract Bisphosphonates are prescribed to treat excessive bone resorption in patients with osteoporosis. However, its use is associated with potential adverse effects such as medication-related osteonecrosis of the jaw, prompting the introduction of the drug holiday concept in patients prior to dentoalveolar surgery. Furthermore, bisphosphonate discontinuation has been studied in vivo, in humans, and in animal models. However, it is not known whether this approach could affect bone cells in vitro. Therefore, the objective of this study was to investigate the potential effects of bisphosphonate discontinuation on pre-osteoblast and osteoblast activities in vitro. Methodology Pre-osteoblasts (MC3T3) and osteoblasts were treated with bisphosphonate (alendronate) at concentrations of 1, 5, and 10 µM. Alendronate was then withdrawn at different time points. The negative control consisted of untreated cells (0 µM), while the positive control consisted of cells incubated with alendronate throughout the experiment. Cell viability, cell adhesion, cell cytoskeleton, mineralization, and gene expressions were investigated. Results Pre-osteoblasts and osteoblasts showed a decrease in cell viability after treatment with 5-10 μM alendronate for 4 days or longer. Two days of alendronate discontinuation significantly increased cell viability compared with the positive control. However, these levels did not reach those of the negative control. Bone nodule formation was reduced by alendronate. Discontinuation of alendronate regained bone nodule formation. Longer periods of discontinuation were more effective in restoring nodule formation than shorter periods. Addition of alendronate resulted in an increase in the percentage of dead cells, which, in turn, decreased when alendronate was discontinued. Alendronate affected the cell cytoskeleton by disassembling actin stress fibers. Cell adhesion and cell morphological parameters were also affected by alendronate. Discontinuation of alendronate restored cell adhesion and these parameters. Overall, the highest improvement after alendronate discontinuation was seen at 10 µM. However, alendronate treatment and discontinuation did not affect osteoblast gene expression. Conclusion Discontinuation of alendronate helps to reverse the negative effects of the drug on cell viability, cell adhesion, and mineralization by restoring the cell cytoskeleton. Our data suggest the benefits of drug holiday and/or intermittent strategies for alendronate administration at the cellular level.

JARID1B represses the osteogenic potential of human periodontal ligament mesenchymal cells.

BACKGROUND: Here, we evaluated whether the histone lysine demethylase 5B (JARID1B), is involved in osteogenic phenotype commitment of periodontal ligament cells (PDLCs), by considering their heterogeneity for osteoblast differentiation. MATERIALS AND METHODS: Epigenetic, transcriptional, and protein levels of a gene set, involved in the osteogenesis, were investigated by performing genome-wide DNA (hydroxy)methylation, mRNA expression, and western blotting analysis at basal (without osteogenic induction), and at the 3rd and 10th days of osteogenic stimulus, in vitro, using PDLCs with low (l) and high (h) osteogenic potential as biological models. RESULTS: h-PDLCs showed reduced levels of JARID1B, compared to l-PDLCs, with significant inversely proportional correlations between RUNX2 and RUNX2/p57. Epigenetically, a significant reduction in the global H3K4me3 content was observed only in h-PDLCs. Immunoblotting data reveal a significant reduction in the global H3K4me3 content, at 3 days of induction only in h-PDLCs, while an increase in the global H3K4me3 content was observed at 10 days for both PDLCs. Additionally, positive correlations were found between global H3K4me3 levels and JARID1B gene expression. CONCLUSIONS: Altogether, our results show the crucial role of JARID1B in repressing PDLCs osteogenic phenotype and this claims to pre-clinical protocols proposing JARID1B as a potential therapeutic target.

The Effects of Platelet-Rich Fibrin in the Behavior of Mineralizing Cells Related to Bone Tissue Regeneration-A Scoping Review of In Vitro Evidence.

Platelet-rich fibrin (PRF) is a second-generation blood concentrate that serves as an autologous approach for both soft and hard tissue regeneration. It provides a scaffold for cell interaction and promotes the local release of growth factors. PRF has been investigated as an alternative to bone tissue therapy, with the potential to expedite wound healing and bone regeneration, though the mechanisms involved are not yet fully understood. This review aims to explore the in vitro evidence of PRF's effects on the behavior of mineralizing cells related to bone tissue regeneration. A systematic electronic search was conducted up to August 2023, utilizing three databases: PubMed, Web of Science, and Scopus. A total of 76 studies were selected, which presented in vitro evidence of PRF's usefulness, either alone or in conjunction with other biomaterials, for bone tissue treatment. PRF membranes' influence on the proliferation, differentiation, and mineralization of bone cells is linked to the constant release of growth factors, resulting in changes in crucial markers of bone cell metabolism and behavior. This further reinforces their therapeutic potential in wound healing and bone regeneration. While there are some notable differences among the studies, the overall results suggest a positive effect of PRF on cell proliferation, differentiation, mineralization, and a reduction in inflammation. This points to its therapeutic potential in the field of regenerative medicine. Collectively, these findings may help enhance our understanding of how PRF impacts basic physiological processes in bone and mineralized tissue.

Uso de microvibración e inhibidores de la catepsina K en tratamientos de regeneración ósea dental / Use of micro-vibration and cathepsin K inhibitors in dental bone regeneration treatments

Introducción: el hueso está en remodelación constante para mantener la estructura del esqueleto, tener un ciclo de resorción por los osteoclastos y formación de hueso nuevo a cargo de los osteoblastos; el hueso también es susceptible a enfermedades sistémicas, traumas, edad y trastornos genéticos que afectarán el remodelado óseo, produciendo una pérdida masiva de masa ósea regulado por hormonas, citocinas, enzimas, etcétera. El objetivo es realizar una revisión sistemática de artículos que muestren cambio o alteración al utilizar tratamientos con microvibraciones y farmacológicos sobre la catepsina K en el hueso alveolar. Material y métodos: para realizar una comparación entre la efectividad del tratamiento a base de microvibraciones y con inhibidores de la catepsina K, se realizó una revisión sistemática en nueve bases de datos (Wiley Online Library, PubMed, Google Academic, Scopus, ScienceDirect, SciELO, Medline, EBSCO y Springer Link). La población de estudio fueron ratas y ratones. Resultados: en este estudio se incluyeron 20 artículos cuya investigación se realizó en estudios clínicos. En los resultados podemos observar cómo todos los tratamientos de alguna forma mejoran el proceso de remodelado óseo. Es difícil comparar cuál de los tratamientos dentro de cada grupo es mejor que otro, debido a que los resultados expresados son cualitativos. Conclusión: acorde a los resultados expresados se opta por realizar un tratamiento con microvibraciones debido a que el uso de inhibidores de la catepsina K aún no se encuentra completamente desarrollado y no se comprenden sus consecuencias debido a su manera sistémica de actuar (AU)

Introduction: the bone is in constant remodeling to maintain the skeletal structure, having a cycle of resorption by osteoclasts and formation of new bone by osteoblasts, the bone is also susceptible to systemic diseases, trauma, age and genetic disorders that affect bone remodeling, producing a massive loss of bone mass regulated by hormones, cytokines, enzymes, etcetera. The objective is to perform a systematic review of articles that show a change or alteration when using micro-vibration and pharmacological treatments on cathepsin K in the alveolar bone. Material and methods: in order to make a comparison between the effectiveness of micro-vibration and cathepsin K inhibitor treatments, a systemic review was carried out in nine databases (Wiley Online Library, PubMed, Google Academic, Scopus, ScienceDirect, SciELO, Medline, EBSCO and Springer Link). The study population was rats and mice. Results: this study included 20 articles whose research was carried out in clinical studies. In the results we can see how all the treatments in some way improve the bone remodeling process, it is difficult to compare which treatment within each group is better than the other, because the results expressed are qualitative. Conclusion: according to the results expressed, it is decided that it is better to perform a treatment with micro vibrations because the use of cathepsin K inhibitors are not yet fully developed and their consequences are not understood due to their systemic way of acting (AU)

Effect of osteoblasts on osteoclast differentiation and activity induced by titanium with nanotopography.

Titanium with nanotopography (Ti Nano) favors osteoblast differentiation and attenuates the osteoclast inhibitory effects on osteoblasts. Because the interactions between nanotopography and osteoclasts are underexplored, the aims of this study were to evaluate the effects of Ti Nano on osteoclast differentiation and activity, and the influence of osteoblasts on osteoclast-Ti Nano interaction. The discs were conditioned with a mixture of 10 N H2SO4 and 30% aqueous H2O2 to create Ti Nano and non-conditioned Ti discs were used as control (Ti Control). Osteoclasts were cultured on Ti Control and Ti Nano in the presence of osteoblasts in an indirect co-culture system. Also, osteoclasts were cultured on polystyrene and calcium phosphate plates in conditioned media by osteoblasts grown on Ti Control and Ti Nano. While Ti Control exhibited an irregular and smooth surface, Ti Nano presented nanopores distributed throughout the whole surface. Additionally, anisotropy was higher on Ti Nano than Ti Control. Nanotopography favored the gene expression of osteoclast markers but inhibited osteoclast differentiation and activity, and the presence of osteoblasts enhanced the effects of Ti Nano on osteoclasts. Such findings were mimicked by conditioned medium of osteoblasts cultured on Ti Nano, which reduced the osteoclast differentiation and activity. In conclusion, our results indicated that nanotopography regulates osteoblast-osteoclast crosstalk and further investigations should focus the impact of these bone cell interactions on Ti osseointegration.

Chitosan, Gelatin, and Collagen Hydrogels for Bone Regeneration.

Hydrogels are versatile biomaterials characterized by three-dimensional, cross-linked, highly hydrated polymeric networks. These polymers exhibit a great variety of biochemical and biophysical properties, which allow for the diffusion of diverse molecules, such as drugs, active ingredients, growth factors, and nanoparticles. Meanwhile, these polymers can control chemical and molecular interactions at the cellular level. The polymeric network can be molded into different structures, imitating the structural characteristics of surrounding tissues and bone defects. Interestingly, the application of hydrogels in bone tissue engineering (BTE) has been gathering significant attention due to the beneficial bone improvement results that have been achieved. Moreover, essential clinical and osteoblastic fate-controlling advances have been achieved with the use of synthetic polymers in the production of hydrogels. However, current trends look towards fabricating hydrogels from biological precursors, such as biopolymers, due to the high biocompatibility, degradability, and mechanical control that can be regulated. Therefore, this review analyzes the concept of hydrogels and the characteristics of chitosan, collagen, and gelatin as excellent candidates for fabricating BTE scaffolds. The changes and opportunities brought on by these biopolymers in bone regeneration are discussed, considering the integration, synergy, and biocompatibility features.