Number Of Osteoblasts Research Articles

In vivo study of porous NiTi cryotweezers for bone tissue cryotherapy

This study examined the effects of liquid nitrogen vapor on osteogenesis in the rabbit femur. Cryotweezers made of porous nickel titanium alloy (nitinol or NiTi) obtained by self-propagating high temperature synthesis were used in this experiment. The porous structure of the cryotweezers allows them to hold up to 10 g of liquid nitrogen after being immersed for 2 minutes, which completely evaporates after 160 seconds. To study the effects of liquid nitrogen evaporation on osteogenesis, a rabbit femur was perforated. The formed holes were subjected to cryotherapy with varying exposure times. It was found that a 3 second exposure time stimulates osteogenesis, which was manifested in a greater number of osteoblasts in the regenerate compared to the control sample without liquid nitrogen. It was observed that increasing the exposure to 6, 9 or 12 seconds had a destructive effect, to varying degrees. The most severe damage was exerted by a 12 second exposure, which resulted in the formation of osteonecrosis areas. In the samples exposed to 6 and 9 seconds of cryotherapy, destruction of the cytoplasm of osteocytes and osteoclasts was observed.

Polysacharide of Agaricusblazei 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.

Perbedaan Jumlah Hitung Osteoblas pada Pergerakan Ortodontik Gigi Setelah Pemberian Jintan Hitam

Osteoblasts are important for orthodontic tooth movement because they influence the activity of bone formation on the tension area. The administration of natural ingredients such as black cumin is proven to increase the number of osteoblasts because it contains thymoquinone as antioxidants to accelerate the process of tooth movement. The study aims to determine the differences in osteoblast count and their effect on the orthodontic movement of teeth after oral administration of black cumin. The method used in this research is experimental laboratory in vivo with a randomized post-test only control group design using 16 male Sprague-Dawley rat samples that were devided into four groups: the control group (K) with distilled water for 7 and 14 days, also the treatment group (P) with black cumin (Nigella sativa) for 7 and 14 days Elastomeric separators were placed on the upper jaw central incisors (right central incisor) using a separator applier to provide orthodontic mechanical force conditions. Alveolar bone tissue samples were taken after treatment then the number of osteoblasts was calculated histologically. Data were anaylzed using One Way Anova Test and LSD (p<0.05). Result of this research indicated that there was an increase in the number of osteoblasts in orthodontic movement after oral administration of black cumin.

Abstract 2761: Activating RET mutations promotes osteoblastic bone metastasis by inhibiting osteoclastogenesis and stimulating osteoblast activity via regulation of osteoprotegerin

Abstract Bone metastases (BM) are a source of increased mortality and significant morbidity in patients with medullary thyroid cancer (MTC), with ~50% survival at five years post-diagnosis. MTC causes osteoblastic, osteolytic, or mixed lesions, yet the underlying mechanisms are unknown. The RET proto-oncogene encodes a transmembrane tyrosine kinase receptor and is the driver oncogene in ~60% of MTC cases where a germline or somatic activating mutation results in ligand-independent constitutive activation of the receptor. However, the role of RET mutations in the genesis of bone metastasis lesions is unknown. We show that activating RET mutations promotes an osteoblastic phenotype in mice implanted with patient-derived MTC cells by increasing bone formation and decreasing bone resorption. We found that the radiographic appearance of osteoblastic lesions differed between the types of RET mutations (C634W and M918T). MTC cells with RETC634W mutation showed a four-fold increase in bone mineral density, trabecular bone volume, number, and thickness with a decreased number of osteoblasts compared to the non-tumor-bearing femur. TRAP staining revealed that osteoclast numbers per long bone were reduced in the injected femur compared to the control. In contrast, the MTC-RETM918T mutation showed an increased cortical thickness and porosity with reduced medullary area and increased bone formation rate compared to the non-tumor bearing femur. MTC cells formed tumors with extensive mineralized tissue, composed of bone matrix surrounded by osteoblast-like cells and osteoid. The knockdown of RET in the MTC-RETM918T model significantly reduced cortical thickness and increased the number of osteoclasts per bone surface. We observed increased osteoprotegerin (OPG) expression in MTC-bearing femurs compared to controls, suggesting decreased bone resorption. The factors secreted by MTC cells, including OPG, inhibited osteoclast formation from primary bone marrow cells and Raw264 cells. In addition, RET knockdown by shRNA in MTC cells decreased OPG expression. Moreover, the MTC-conditioned media (CM) increased osteoblast differentiation and mineralization of the primary culture of pre-osteoblasts isolated from calvarial bone, long bones, and MC3T3 cells. The conditioned media of RET-depleted cells inhibits osteoblast differentiation and mineralization. The expression of alkaline phosphatase, osteocalcin, OPG, and osterix increased in pre-osteoblast incubated with MTC-CM. Compared to primary non-metastatic tumors, the OPG expression increases in tissues of sporadic MTC bone metastases harboring RETM918T mutation. These results suggest that MTC with RET-activating mutations induces osteoblastic bone metastasis due to decreased bone resorption and increased bone formation. Citation Format: Rozita Bagheri-Yarmand, Joseph L. Kidd, Gabriel M. Pagnotti, Trupti Trivedi, Leah Guerra, Xinhai Wan, Jian Song, Sue-Hwa Lin, Theresa A Guise. Activating RET mutations promotes osteoblastic bone metastasis by inhibiting osteoclastogenesis and stimulating osteoblast activity via regulation of osteoprotegerin [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2761.

Moringa oleifera leaf extract promotes the healing of critical sized bone defects in the mandibles of rabbits

ObjectiveThe search for an osteopromotive material that enhances the efficacy of alloplasts in reconstructive surgeries has been going on for years. This study aimed to histologically and histomorphometrically evaluate the efficiency of Moringa oleifera leaf extract as an osteopromotive biomaterial.DesignThe study is a prospective randomized controlled animal study. 24 adult male New Zealand rabbits were equally allocated into test and control groups. Critical-sized bone defects were created in the edentulous areas of the mandibles of rabbits. The defects of the control group were filled with Beta-tricalcium Phosphate, while the defects of the test group were filled with Beta-tricalcium Phosphate combined with Moringa oleifera leaf extract. The results were evaluated histologically and histomorphometrically.ResultsHistological and histomorphometric analysis showed a significant increase in the surface area of bone and the number of osteoblasts in test groups compared to those in the control groups.ConclusionMoringa oleifera leaf extract has a positive effect on bone regeneration in critical-sized bone defects.

Chenopodium Ambrosioides Linn Mitigates Bone Loss in Rats with Periodontitis.

Periodontitis is an inflammatory disease that causes bone loss. Some patients do not respond well to the classic treatment and need therapies that minimize bone loss, the main sequel of the disease. Chenopodium ambrosioides L. has stood out due to its anti-inflammatory and anti-oxidative activities. However, no study has yet investigated its effect on periodontitis. This study aimed to evaluate the bone protective effect of Chenopodium ambrosioides L. (CAL) extract on ligature-induced periodontitis model in rats. For this, a pre-clinical assay was performed, using male Wistar rats divided into 3 groups: Naive (N) (n=6), not submitted to any procedure; Saline (SAL) (n=6), submitted to ligature-induced periodontitis and receiving 2 ml/kg of 0.9% saline solution; and CAL extract, which was subdivided into 3 subgroups (n=6/subgroup) receiving the CAL at 3 (CAL3), 10 (CAL10) or 30 mg/kg (CAL30). All agents were given, by oral gavage, 30 min before periodontitis induction and daily until euthanasia (11th day). By then, maxillae were removed for macroscopic, histological, and histometric analyses. Kidneys, liver, and stomach were collected to evaluate the safety of CAL extract. High-performance liquid chromatography (HPLC) assay was used to investigate the flavonoid content in the extract. Chenopodium ambrosioides L. extract at 30mg/kg showed a reduction by 58% in bone loss marked by an increase (+35%) in the number of osteoblasts and a reduction (-51%) on the number of osteoclasts (p< 0.05). No significant alteration in the liver, kidney, or stomach was seen. Rutin was the main flavonoid found. In summary, it was observed that Chenopodium ambrosioides L. extract has shown important anti-inflammatory and bone anabolic and anti-resorptive properties without causing toxicity in the main organs. Rutin, as the main flavonoid of the extract, seems to be responsible for the beneficial effect of this agent.

Tmem119 is involved in bone anabolic effects of PTH through enhanced osteoblastic bone formation in mice

The intermittent administration of parathyroid hormone (PTH) exerts potent bone anabolic effects, which increase bone mineral density (BMD) and reduce fracture risk in osteoporotic patients. However, the underlying mechanisms remain unclear. Tmem119 has been proposed as a factor that is closely linked to the osteoblast phenotype, and we previously reported that PTH enhanced the expression of Tmem119 in mouse osteoblastic cells. However, roles of Tmem119 in the bone anabolic effects of PTH in vivo remain unknown. We herein investigated the roles of Tmem119 in bone anabolic effects of PTH using Tmem119-deficient mice. Tmem119 deficiency significantly reduced PTH-induced increases in trabecular bone volume and cortical BMD of femurs. Effects of Tmem119 deficiency on bone mass seemed predominant in female mice. Histomorphometric analyses with calcein labeling showed that Tmem119 deficiency significantly attenuated PTH-induced increases in the rates of bone formation and mineralization as well as numbers of osteoblasts. Moreover, Tmem119 deficiency significantly blunted PTH-induced decreases in phosphorylation of β-catenin and increases in alkaline phosphatase activity in osteoblasts. In conclusion, the present results indicate that Tmem119 is involved in bone anabolic effects of PTH through osteoblastic bone formation partly related to canonical Wnt-β-catenin signaling in mice.

Alterations in compositional and cellular properties of the subchondral bone are linked to cartilage degeneration in hip osteoarthritis

ObjectiveThe subchondral bone is an emerging regulator of osteoarthritis (OA). However, knowledge of how specific subchondral alterations relate to cartilage degeneration remains incomplete. MethodFemoral heads were obtained from 44 patients with primary OA during total hip arthroplasty and from 30 non-OA controls during autopsy. A multiscale assessment of the central subchondral bone region comprising histomorphometry, quantitative backscattered electron imaging, nanoindentation, and osteocyte lacunocanalicular network characterization was employed. ResultsIn hip OA, thickening of the subchondral bone coincided with a higher number of osteoblasts (controls: 3.7±4.5 mm-1, OA: 16.4±10.2 mm-1, age-adjusted mean difference 10.5 mm-1 [95% CI 4.7 to 16.4], p<0.001) but a similar number of osteoclasts compared to controls (p=0.150). Furthermore, higher matrix mineralization heterogeneity (CaWidth, controls: 2.8±0.2 wt%, OA: 3.1±0.3 wt%, age-adjusted mean difference 0.2 wt% [95% CI 0.1 to 0.4], p=0.011) and lower tissue hardness (controls: 0.69±0.06 GPa, OA: 0.67±0.06 GPa, age-adjusted mean difference -0.05 GPa [95% CI -0.09 to -0.01], p=0.032) were detected. While no evidence of altered osteocytic perilacunar/canalicular remodeling in terms of fewer osteocyte canaliculi was found in OA, specimens with advanced cartilage degeneration showed a higher number of osteocyte canaliculi and larger lacunocanalicular network area compared to those with low-grade cartilage degeneration. Multiple linear regression models indicated that several subchondral bone properties, especially osteoblast and osteocyte parameters, were closely related to cartilage degeneration (R2 adjusted=0.561, p<0.001). ConclusionSubchondral bone properties in OA are affected at the compositional, mechanical, and cellular levels. Based on their strong interaction with cartilage degeneration, targeting osteoblasts/osteocytes may be a promising therapeutic OA approach. Data and materials availabilityAll data are available in the main text or the supplementary materials.

A personalized biomimetic dual-drug delivery system via controlled release of PTH1-34 and simvastatin for in situ osteoporotic bone regeneration.

Patients with osteoporosis often encounter clinical challenges of poor healing after bone transplantation due to their diminished bone formation capacity. The use of bone substitutes containing bioactive factors that increase the number and differentiation of osteoblasts is a strategy to improve poor bone healing. In this study, we developed an in situ dual-drug delivery system containing the bone growth factors PTH1-34 and simvastatin to increase the number and differentiation of osteoblasts for osteoporotic bone regeneration. Our system exhibited ideal physical properties similar to those of natural bone and allowed for customizations in shape through a 3D-printed scaffold and GelMA. The composite system regulated the sustained release of PTH1-34 and simvastatin, and exhibited good biocompatibility. Cell studies revealed that the composite system reduced osteoblast death, and promoted expression of osteoblast differentiation markers. Additionally, by radiographic analysis and histological observation, the dual-drug composite system demonstrated promising bone regeneration outcomes in an osteoporotic skull defect model. In summary, this composite delivery system, comprising dual-drug administration, holds considerable potential for bone repair and may serve as a safe and efficacious therapeutic approach for addressing bone defects in patients with osteoporosis.

Intermittent Methionine Restriction Reduces Marrow Fat Accumulation and Preserves More Bone Mass than Continuous Methionine Restriction.

Continuous methionine restriction (MR) is one of only a few dietary interventions known to dramatically extend mammalian healthspan. For example, continuously methionine-restricted rodents show less age-related pathology and are up to 45% longer-lived than controls. Intriguingly, MR is feasible for humans, andanumberofstudieshavesuggestedthatmethionine-restrictedindividualsmayreceivesimilarhealthspan benefits as rodents. However, long-term adherence to a continuously methionine-restricted diet is likely to be challenging (or even undesirable) for many individuals. To address this, we previously developed an intermittent version of MR (IMR) and demonstrated that it confers nearly identical metabolic health benefits to mice as the continuous intervention, despite having a relatively short interventional period (i.e., only three days per week). We also observed that female mice undergoing IMR show a more pronounced amelioration of diet-induced dysglycemia than continuously methionine-restricted counterparts, while male mice undergoing IMR retain more lean body mass as compared with continuously methionine-restricted controls. Prompted by such findings, we sought to determine other ways in which IMR might compare favorably with continuous MR. While it is known that continuous MR has deleterious effects on bone in mice, including loss of both trabecular and cortical bone, we considered that mice undergoing IMR might retain more bone mass. Here, we report that, as compared with continuous MR, IMR results in a preservation of both trabecular and cortical bone, as well as a dramatic reduction in the accumulation of marrow fat. Consistent with such findings, mechanical testing revealed that the bones of intermittently methionine-restricted mice are significantly stronger than those of mice subjected to the continuous intervention. Finally, static histomorphometric analyses suggest that IMR likely results in more bone mass than that produced by continuous MR, primarily by increasing the number of osteoblasts. Together, our results demonstrate that the more practicable intermittent form of MR not only confers similar metabolic health benefits to the continuous intervention but does so without markedly deleterious effects on either the amount or strength of bone. These data provide further support for the use of IMR in humans.

Post-Orthodontic Relapse Prevention through Administration of a Novel Synthetic Carbonated Hydroxyapatite-Chitosan Hydrogel Derived from Blood Cockle Shell (Anadara granosa L.).

Relapse during passive orthodontic treatment is a major issue, with 70-90% frequency. This study examines whether blood cockle shells may be used to extract carbonated hydroxyapatite (CHA)-chitosan (CS). This study also aims to analyze the effect of CHA-CS on orthodontic relapse in rats. This study utilized 18 male Wistar rats which were randomly divided into two groups: CHA-CS and the control group (CG). The rats were subjected to a 35 cN orthodontic force for a duration of 7 days, after which the rats were conditioned to be passive. During this phase, the CHA-CS group received daily administration of CHA-CS hydrogel derived from the blood cockle shell. Subsequently, the appliances were detached to facilitate relapse. The distance between the mesial tips was measured using a digital caliper at three consecutive time points: 1, 5, and 7 days after debonding. The number of osteoblasts, osteoclasts, and fibroblasts was examined using hematoxylin-eosin staining. The data were subjected to statistical analysis using a t-test. The relapse distance of the CHA-CS group was lower than that of the control groups on day 7. Histological examinations using hematoxylin-eosin (HE) staining showed a significant increase in osteoblasts, a decrease in osteoclasts, and an increase in fibroblasts during orthodontic relapse movement (p < 0.05). This study found that blood cockle shell-derived CHA-CS may reduce orthodontic relapse by increasing osteoblasts and fibroblasts and by reducing the osteoclast number in rats.

Genetic analysis, phenotype spectrum and functional study of rare osteogenesis imperfecta caused by CRTAP Variants.

Deficiency of cartilage-associated protein (CRTAP) can cause extremely rare autosomal recessive osteogenesis imperfecta (OI) type VII. We investigated the pathogenic mechanisms of CRTAP variants through functional studies on OI patient-derived bones. Two nonconsanguineous families with CRTAP mutations were included, and their phenotypes and genotypes were evaluated. Bone specimens were obtained from one OI patient and a normal control during orthopedic surgery. The impacts of the novel variant on the CRTAP transcript were confirmed. The expression levels of CRTAP mRNA and CRTAP protein were analyzed. The quantification of prolyl 3-hydroxylation in the α1 chain of type I collagen was evaluated. Patients with OI type VII had early-onset recurrent fractures, severe osteoporosis, and bone deformities. The c.621 + 1G > A and c.1153-3C > G mutations were identified in CRTAP in the OI patients. The c.621 + 1G > A variant was a novel mutation that could impair mRNA transcription, leading to a truncated CRTAP protein. In a patient with c.621 + 1G > A and c.1153-3C > G mutations in CRTAP, the mRNA and protein levels of CRTAP in osteoblasts were significantly decreased, and the osteoid volume and osteoblast numbers were markedly reduced compared with those in the normal control individual. This was simultaneously accompanied by significantly reduced prolyl 3-hydroxylation of Pro986 in the α1 chain of type I collagen and invisible active bone formation in bone. The novel c.621 + 1G > A mutation in CRTAP expands the genotypic spectrum of type VII OI. Biallelic mutations of c.621 + 1G > A and c.1153-3C > G in CRTAP can lead to reduced CRTAP mRNA and deficient CRTAP protein in osteoblasts, which reduces 3-hydroxylation in Pro986 of the α1 chain of type I collagen and impairs bone formation, thus contributing to severe OI type VII.

Runx2 deletion in hypertrophic chondrocytes impairs osteoclast mediated bone resorption

Deletion of Runx2 gene in proliferating chondrocytes results in complete failure of endochondral ossification and perinatal lethality. We reported recently that mice with Runx2 deletion specifically in hypertrophic chondrocytes (HCs) using the Col10a1-Cre transgene survive and exhibit enlarged growth plates due to decreased HC apoptosis and cartilage resorption. Bulk of chondrogenesis occurs postnatally, however, the role of Runx2 in HCs during postnatal chondrogenesis is unknown. Despite limb dwarfism, adult homozygous (Runx2HC/HC) mice showed a significant increase in length of growth plate and articular cartilage. Consistent with doubling of the hypertrophic zone, collagen type X expression was increased in Runx2HC/HC mice. In sharp contrast, expression of metalloproteinases and aggrecanases were markedly decreased. Impaired cartilage degradation was evident by the retention of significant amount of safranin-O positive cartilage. Histomorphometry and μCT uncovered increased trabecular bone mass with a significant increase in BV/TV ratio, trabecular number, thickness, and a decrease in trabecular space in Runx2HC/HC mice. To identify if this is due to increased bone synthesis, expression of osteoblast differentiation markers was evaluated and found to be comparable amongst littermates. Histomorphometry confirmed similar number of osteoblasts in the littermates. Furthermore, dynamic bone synthesis showed no differences in mineral apposition or bone formation rates. Surprisingly, three-point-bending test revealed Runx2HC/HC bones to be structurally less strong. Interestingly, both the number and surface of osteoclasts were markedly reduced in Runx2HC/HC littermates. Rankl and IL-17a ligands that promote osteoclast differentiation were markedly reduced in Runx2HC/HC mice. Bone marrow cultures were performed to independently establish Runx2 and hypertrophic chondrocytes role in osteoclast development. The culture from the Runx2HC/HC mice formed significantly fewer and smaller osteoclasts. The expression of mature osteoclast markers, Ctsk and Mmp9, were significantly reduced in the cultures from Runx2HC/HC mice. Thus, Runx2 functions extend beyond embryonic development and chondrocyte hypertrophy by regulating cartilage degradation, osteoclast differentiation, and bone resorption during postnatal endochondral ossification.

Loss of the auxiliary α2δ1 voltage-sensitive calcium channel subunit impairs bone formation and anabolic responses to mechanical loading.

Voltage-sensitive calcium channels (VSCCs) influence bone structure and function, including anabolic responses to mechanical loading. While the pore-forming (α1) subunit of VSCCs allows Ca2+ influx, auxiliary subunits regulate the biophysical properties of the pore. The α2δ1 subunit influences gating kinetics of the α1 pore and enables mechanically induced signaling in osteocytes; however, the skeletal function of α2δ1 in vivo remains unknown. In this work, we examined the skeletal consequences of deleting Cacna2d1, the gene encoding α2δ1. Dual-energy X-ray absorptiometry and microcomputed tomography imaging demonstrated that deletion of α2δ1 diminished bone mineral content and density in both male and female C57BL/6 mice. Structural differences manifested in both trabecular and cortical bone for males, while the absence of α2δ1 affected only cortical bone in female mice. Deletion of α2δ1 impaired skeletal mechanical properties in both sexes, as measured by three-point bending to failure. While no changes in osteoblast number or activity were found for either sex, male mice displayed a significant increase in osteoclast number, accompanied by increased eroded bone surface and upregulation of genes that regulate osteoclast differentiation. Deletion of α2δ1 also rendered the skeleton insensitive to exogenous mechanical loading in males. While previous work demonstrates that VSCCs are essential for anabolic responses to mechanical loading, the mechanism by which these channels sense and respond to force remained unclear. Our data demonstrate that the α2δ1 auxiliary VSCC subunit functions to maintain baseline bone mass and strength through regulation of osteoclast activity and also provides skeletal mechanotransduction in male mice. These data reveal a molecular player in our understanding of the mechanisms by which VSCCs influence skeletal adaptation.

The Effect of Ramania Leaves Extract Gel (Bouea macrophylla Griff) on the Number of Osteoblast (in vivo Study of Post Extraction in Wistar Rats (Rattus norvegicus))

The Effect of Ramania Leaves Extract Gel (Bouea macrophylla Griff) on the Number of Osteoblast (in vivo Study of Post Extraction in Wistar Rats (Rattus norvegicus))

HISTOMORPHOMETRIC ASSESSMENT OF CHANGES THE STRUCTURAL COMPONENTS OF THE BONE IN RATS WITH CHRONIC CHOLESTASIS WITH CORRECTION OF THE COMPLEX FROM HEPATOPROTECTOR AND SORBENT

Problem. The disruption of the gastric duct in cholestasis causes insufficient absorption in the small intestine of macro- and microelements and fat-rich vitamins (A, D, E, K), which are necessary for healthy processes, and remodeling of bone tissue. To reduce pathological changes in bone tissue diseases of the hepatobiliary system in rats statement in cholestasis, need a comprehensive approach [6]. In the core of the preventive complex one can see a hepatoprotector, which, due to its main components (lecithin, quercetin), possesses the liver protecting properties, as well as has anti-inflammatory and bile-diluting effects, and a sorbent. Aim. To conduct a histomorphometric research of the femur in rats with chronic cholestasis and evaluate the effectiveness of the prophylactic complex. Methods. The follow-up study was carried out on male rats, divided into three groups: 1st group – intact, 2nd group – rats with simulated chronic cholestasis, 3rd group – rats, who, in parallel with the development of chronic cholestasis pathology, carried out prevention. Cholestasis in rats was modeled by ligation of the biliary duct under thiopental anesthesia [9]. A hepatoprotector at a dose of 500 mg/kg and a sorbent at a dose of 1 g/kg were administered to group 3 of the animals once over a period of 4 months. Histological analysis and photography of sections of the stegnus cyst were carried out using an additional light microscope and a camera for an Olympus LC30 microscope (Japan). Morphometric studies of rat femur were carried out using the following parameters: volume (%) of the articular epiphyseal cartilage, volume (%) of the cartilage, volume (%) of the cerebrum and the number of osteoblasts per the particular area. The main results. Certain histological changes in the epiphysis of the femoral bone were found in rats with chronic cholestasis, namely, noticeable delamination of the periosteum was noted. In the deep layers of the cartilage, a decrease in the number of isogenic groups was noted, in addition, they contained a smaller number of chondrocytes. Desolation of individual lacunae, a decrease in the number of osteoblasts, and thinning of bone trabeculae were also observed, indicating certain pathological changes in bone tissue. Analysis of the morphometric parameters of the femur in rats with chronic cholestasis revealed a decrease in the specific volume of the cartilage of the articular surfaces by 25.8%, a decrease in the specific volume of the bone marrow and the number of osteoblasts by 14.4% and 39.4%, respectively, and as well as an increase of 33.1% in the specific volume of bone beams in relation to the control group. The introduction of the prophylactic complex contributed to a significant increase in the specific volume of the cartilage of the articular surfaces – by 17.2%, the specific volume of bone marrow by 42.9%, the average number of osteoblasts by 34.9%, and a decrease in the specific volume of bone beams by 31 .7% relative to the group of animals with chronic cholestasis. That is, the use of a prophylactic complex, which consisted of a hepatoprotector and a sorbent, effectively eliminated pathological changes in bone tissue that arose against the background of the development of chronic cholestasis. Conclusions. The formation of chronic cholestasis leads to pathological changes in the cartilaginous tissue of the epiphysis of the femur of the animals under study, and it itself changes the volume of cartilage of the subglobular surfaces and causes destruction of the main components in bone tissue (reduces the volume of bone marrow and the number of osteoblasts at the background of the growth the volume of bone beams). The effectiveness of prophylactic in the elimination of pathological changes in bone tissue at the background of chronic cholestasis has manifested itself as a hepatoprotective, antioxidant, anti-inflammatory and anti-inflammatory hepatoprotector and those combined with a sorbent.

Morphological features of bone regenerate when using bone plastic material based on collagen hydrogel in an experiment

Background: Bone-plastic materials of various origin are used when it is necessary to restore or increase the volume of bone tissue of the jaws. Collagen hydrogel of xenogenic origin is a relatively new form of materials used for bone grafting, and is of interest for studying its osteoplastic properties.&#x0D; Aim: Morphological evaluation of osteoplastic properties of a material based on collagen hydrogel in an experiment.&#x0D; Material and methods: to evaluate the osteoplastic properties of collagen hydrogel, an experimental study was conducted on laboratory animals. A model of a critical defect in the cranial vault of rats was chosen for the study. In the experimental group, the defect was filled with xenogenic bone matrix and collagen hydrogel. In the comparison group, the defect was filled with xenogenic bone matrix. morphological evaluation of bone regeneration of samples of the experimental group and the comparison group was performed at different study periods.&#x0D; Results and their discussion:&#x0D; After the first month of observation, the histological picture in the samples of the experimental group and the comparison group had no significant differences. After two months of the study, the formation of an osseomucoid and the appearance of an insignificant number of osteoblasts were observed in the experimental group, while in the comparison group the stromal component was represented only by collagen fibers. After three months of observation, the organization of the stromal component was determined in the comparison group, single osteoblasts were observed, whereas in the experimental group the stromal component was partially replaced by a bone plate, and the cellular composition was represented by osteoblasts, osteocytes and osteoclasts.&#x0D; Conclusion: The addition of collagen hydrogel to the bone plastic material provides not only acceleration of the process of osteoreparation, but also the formation of a regenerate having the correct histoarchitectonics. The issue of using collagen hydrogel as a component of bone-plastic materials is promising and requires further study.

Effect of intraoral administration of parathyroid hormone on osseous and soft tissue healing around implants in ovariectomized rat maxillae.

Intermittent administration of parathyroid hormone (PTH) increases systemic bone mass. However, the effect of PTH on osseous and soft tissue healing around implants in osteoporosis patients remains unclear. This study aimed to investigate the effects of PTH on tissue healing around implants in ovariectomized rats and to compare systemic and intraoral administration routes. Implants were placed at the healed sites of ovariectomized rats 3 weeks after maxillary first molar extraction. Rats were randomly divided into two groups that received either daily systemic subcutaneous or local intraoral PTH administration. Maxillae were dissected to examine bone architectures with micro-computed tomography images. Histomorphometric and immunohistochemical analyses were performed to evaluate osseous and soft tissue healing around the implants. Regardless of the administration route, PTH significantly increased bone area and the numbers of osteoblasts, osteoclasts, and osteocytes in the first and second inside and outside areas of implant threads, in addition to decreasing the number of sclerostin+ osteocytes. However, the intraoral PTH administration route was superior to the systemic route by significantly improving bone quality and promoting collagen production in the connective tissue around implants. Parathyroid hormone administration promoted both osseous and soft tissue healing around implants, irrespective of administration route. Interestingly, intraoral administration improved the evaluated parameters more than systemic administration. Thus, the intraoral route could become a useful treatment strategy for implant treatment in osteoporosis patients.

The Effects of Thymoquinone Loaded in Alginate Scaffold on Bone Regeneration in Rabbit Mandible Defect: The Effects of Thymoquinone on Bone Regeneration

Background: Thymoquinone (TQ) has some beneficial roles in bone repair. Local administration of the drugs by loading them into a scaffold leads to releasing higher concentrations of a drug in the appropriate position. This study was conducted to evaluate the effects of the local administration of TQ loaded in an alginate scaffold on bone regeneration in rabbit mandibular defect. Materials and Methods: In this experimental study, male rabbits with mandible defect were divided into 3 groups that received either alginate containing 50µM TQ, alginate or remained untreated. Then each group was subdivided into 2 groups that followed for 4 and 8 weeks (n=5). The radiological opacity, histopathology, and histomorphometrical analysis were done and data were analyzed by ANOVA and Tukey. Results: Radiological examination indicated that the presence of TQ had no significant effect on the turbidity of the images (P=0.595). TQ treatment significantly increased the bone area after 4 (P=0.011, P=0.0021, respectively) and 8 weeks (8w P=0.019, P&lt;0.001, respectively) compared to alginate-treated and control defects. TQ also elevated the number of osteocytes (4wP&lt;0.001, P=0.001 and 8w P&lt;0.001, P&lt;0.001, respectively) and osteoblasts (P&lt;0.001, P&lt;0.001, respectively) compared to the group receiving alginate and control. However, at 8 weeks, the number of osteoblasts was statistically similar in all the groups. In this week, although the average number of osteoblasts in the defects treated with TQ was significantly higher than the control group (P=0.01), it was similar to the group that received alginate. Conclusion: It seems that alginate containing TQ has positive effects on bone healing. TQ can be suggested as a good additive to improve bone healing and accelerate bone repair.

The influence of uremic toxins on low bone turnover disease in chronic kidney disease.

Uremic toxins play a crucial role in the development of low bone turnover disease in chronic kidney disease (CKD) through the induction of oxidative stress. This oxidative stress disrupts the delicate balance between bone formation and resorption, resulting in a decline in both bone quantity and quality. Reactive oxygen species (ROS) activate nuclear factor kappa-B and mitogen-activated protein kinase signaling pathways, promoting osteoclastogenesis. Conversely, ROS hinder osteoblast differentiation by facilitating the binding of Forkhead box O proteins (FoxOs) to β-catenin, triggering apoptosis through FoxOs-activating kinase phosphorylation. This results in increased osteoblastic receptor activator of nuclear factor kappa-B ligand (RANKL) expression and decreased nuclear factor erythroid 2-related factor 2 levels, compromising antioxidant defenses against oxidative damage. As CKD progresses, the accumulation of protein-bound uremic toxins such as indoxyl sulfate (IS) and p-cresyl sulfate (PCS) intensifies oxidative stress, primarily affecting osteoblasts. IS and PCS directly inhibit osteoblast viability, induce apoptosis, decrease alkaline phosphatase activity, and impair collagen 1 and osteonectin, impeding bone formation. They also reduce cyclic adenosine 3',5'-monophosphate (cAMP) production and lower parathyroid hormone (PTH) receptor expression in osteoblasts, resulting in PTH hyporesponsiveness. In summary, excessive production of ROS by uremic toxins not only reduces the number and function of osteoblasts but also induces PTH hyporesponsiveness, contributing to the initiation and progression of low bone turnover disease in CKD.