Bone Remodeling Process Research Articles

SCLEROSTIN-MEDIATED IMPAIRED OSTEOGENESIS BY FIBROBLAST-LIKE SYNOVIOCYTES IN THE PARTICLE-INDUCED OSTEOLYSIS MODEL

Wear debris from implant interfaces is the major factor leading to periprosthetic osteolysis. Fibroblast-like synoviocytes (FLSs) populate the intimal lining of the synovium and are in direct contact with wear debris. This study aimed to elucidate the effect of Ti particles as wear debris on human FLSs and the mechanism by which they might participate in the bone remodeling process during periprosthetic osteolysis. FLSs were isolated from synovial tissue from patients, and the condition medium (CM) was collected after treating FLSs with sterilized Ti particles. The effect of CM was analyzed for the induction of osteoclastogenesis or any effect on osteogenesis and signaling pathways. The results demonstrated that Ti particles could induce activation of the NFκB signaling pathway and induction of COX-2 and inflammatory cytokines in FLSs. The amount of RANL in the conditioned medium collected from Ti particle-stimulated FLSs (Ti CM) showed the ability to stimulate osteoclast formation. The Ti CM also suppressed the osteogenic initial and terminal differentiation markers for osteoprogenitors, such as alkaline phosphate activity, matrix mineralization, collagen synthesis, and expression levels of Osterix, Runx2, collagen 1α, and bone sialoprotein. Inhibition of the WNT and BMP signaling pathways was observed in osteoprogenitors after the treatment with the Ti CM. In the presence of the Ti CM, exogenous stimulation by WNT and BMP signaling pathways failed to stimulate osteogenic activity in osteoprogenitors. Induced expression of sclerostin (SOST: an antagonist of WNT and BMP signaling) in Ti particletreated FLSs and secretion of SOST in the Ti CM were detected. Neutralization of SOST in the Ti CM partially restored the suppressed WNT and BMP signaling activity as well as the osteogenic activity in osteoprogenitors. Our results reveal that wear debris-stimulated FLSs might affect bone loss by not only stimulating osteoclastogenesis but also suppressing the bone-forming ability of osteoprogenitors. In the clinical setting, targeting FLSs for the secretion of antagonists like SOST might be a novel therapeutic approach for preventing bone loss during inflammatory osteolysis.

IN VITRO MODELS MIMICKING THE BONE REMODELLING CYCLE

Metabolic bone diseases, such as osteoporosis and osteopetrosis, result from an imbalanced bone remodeling process. In vitro bone models are often used to investigate either bone formation or resorption independently, while in vivo, these processes are coupled. Combining these processes in a co-culture is challenging as it requires finding the right medium components to stimulate each cell type involved without interfering with the other cell type's differentiation. Furthermore, differentiation stimulating factors often comprise growth factors in supraphysiological concentrations, which can overshadow the cell-mediated crosstalk and coupling.To address these challenges, we aimed to recreate the physiological bone remodeling process, which follows a specific sequence of events starting with cell activation and bone resorption by osteoclasts, reversal, followed by bone formation by osteoblasts. We used a mineralized silk fibroin scaffold as a bone-mimetic template, inspired by bone's extracellular matrix composition and organization. Our model supported osteoclastic resorption and osteoblastic mineralization in the specific sequence that represents physiological bone remodeling.We also demonstrated how culture variables, such as different cell ratios, base media, and the use of osteogenic/osteoclast supplements, and the application of mechanical load, can be adjusted to represent either a high bone turnover system or a self-regulating system. The latter system did not require the addition of osteoclastic and osteogenic differentiation factors for remodeling, therefore avoiding growth factor use.Our in vitro model for bone remodeling has the potential to reduce animal experiments and advance in vitro drug development for bone remodeling pathologies like osteoporosis. By recreating the physiological bone remodeling cycle, we can investigate cell-cell and cell-matrix interactions, which are essential for understanding bone physiology and pathology. Furthermore, by tuning the culture variables, we can investigate bone remodeling under various conditions, potentially providing insights into the mechanisms underlying different bone disorders.

Unveiling the Link Between Breast Cancer Treatment and Osteoporosis: Implications for Anticancer Therapy and Bone Health

Background: The interplay between breast cancer treatment and osteoporosis has important consequences for anticancer therapy and patient bone health. Many breast cancer therapies involve hormonal treatments that lower estrogen levels, which can lead to an increased risk of osteoporosis due to reduced bone mineral density. Aromatase inhibitors, chemotherapy, and surgeries such as oophorectomy can further aggravate bone loss, highlighting the necessity of prioritizing bone health during cancer treatment.Objective: This review is aimed at investigating the complex relationship between breast cancer therapies and bone health by examining the molecular and cellular mechanisms through which anticancer treatments lead to bone loss. It also seeks to assess the effects of various treatment options, such as selective estrogen receptor modulators (SERMs) and bisphosphonates, on reducing bone loss and maintaining bone health during cancer therapy.Method: The review explores the mechanisms underlying bone loss in breast cancer patients undergoing treatment, focusing on factors such as estrogen depletion, inflammatory cytokines, and changes in bone remodelling processes. Additionally, it evaluates the efficacy of different therapeutic interventions, including pharmacological treatments like bisphosphonates and third‐generation SERMs, in mitigating bone‐related side effects.Results: The findings indicate a critical need to balance the effectiveness of breast cancer treatments with the preservation of bone health. Pharmacological treatments like bisphosphonates and denosumab have been identified as essential for managing bone health in breast cancer patients. Furthermore, third‐generation SERMs show potential in reducing bone loss associated with cancer therapy.

Serum levels of soluble receptor activator of NF-κβ ligand are under dual, immune and neural effects in postmenopausal women

Background: The receptor activator of NF-κβ (RANK)/RANK ligand/ osteoprotegerin system is essential for osteoclast maturation and activation to induce bone loss, which plays a role in postmenopausal osteoporosis. Estrogen deficiency in postmenopausal women is associated with T-cell mediated inflammation with increased proinflammatory cytokines, such as IL-17A, IL-1, IL-6 and tumor necrosis factor alpha. Bone repair and remodeling processes highlight the role of nerve growth factor β (NGFβ), whose non-neural production is associated with T-cell mediated inflammation. Aims: To investigate the involvement of IL-17A and NGFβ cytokines in the elevation of serum soluble RANK ligand levels in postmenopausal and control women. Methods: Fifty-two postmenopausal and 37 control women were studied for age, body mass index, homeostasis model assessment (HOMA) index, serum levels of IL-17A, NGFβ, soluble RANK ligand (measured by indirect enzyme-linked immunosorbent assay) and estrogen (measured by chemiluminescence assay). Two- and three-way ANOVA (expressed as median with Q1 to Q3) and linear regression analysis were used to evaluate the strength of relationship between soluble RANK ligand levels as dependent and age, serum IL-17A and NGFβ levels as independent variables. Results: A significant difference in age, serum NGFβ and estrogen levels could be demonstrated between postmenopausal and control women (with borderline significance in HOMA indices). The differences in serum IL-17A and NGFβ levels were relevant between categories for body mass index in postmenopausal and control women, but in soluble RANK ligand levels only in postmenopausal women. The increase in soluble RANK ligand levels was greater in elevated IL-17A [101(291.75 to 39.92) vs. 45.24(95.56 to 25.34) ng/ml, p<0.015] and elevated NGFβ [222.2(142.75 to 1086.87) vs. 52.44(25.87 to 76.88) ng/ml, p<0.0001] categories compared to low categories in postmenopause, but not in controls. Both elevated IL-17A and NGFβ levels resulted in the greatest increase in serum levels of soluble RANK ligand [252.27(159.9 to 1099.64) vs. 41.4(35.91 to 59.94) ng/ml, p<0.0001] compared to elevated IL-17A levels alone. Conclusion: Both IL-17A and NGFβ cytokines were involved in the increased serum levels of soluble RANK ligand in postmenopausal women. Their joint involvement in postmenopausal osteoporosis highlighted that neurogenic inflammation may play a critical role in bone loss via greater elevated soluble RANK ligand levels induced by concomitant elevated IL-17A and NGFβ levels.

A inter-relação do movimento dentário ortodôntico em pacientes com periodontite e Diabetes mellitus

ABSTRACT Orthodontic tooth movement is a mechanically induced bone remodeling process aimed at aligning malpositioned teeth. Periodontitis is a polymicrobial infection of the supporting tissues of the teeth that results in the destruction of the periodontium. Diabetes Mellitus is a metabolic disorder that contributes to several types of comorbidities and even premature death of an individual. Due to the high demand of diabetic patients with periodontitis and the need for orthodontic therapy to achieve better periodontal health, we aimed to carry out a bibliographic review on orthodontic tooth movement in patients with periodontitis and diabetes mellitus. The search for articles in this literature review took place between February 2022 and March 2023. The articles were researched, selected and extracted through the database: PUBMED, LILACS and GOOGLE SCHOLAR available online, in the range of years between 1990 and 2022. Diabetes and periodontitis may adversely affect bone remodeling in orthodontic tooth movement. However, despite the need for further long-term studies to elucidate the mechanism of orthodontic tooth movement in diabetic patients with a history of periodontitis, the literature suggests that if there is a well-established periodontal-orthodontic therapy associated with the patient’s glycemic control, the treatment will be successful.

Features of bone remodeling and osteoreparation processes in modeling femoral fracture in genetically modified mice with impaired enzymatic regulation of steroid hormone metabolism

Introduction: The aim of this study was to evaluate the processes of bone remodeling and osteoreparation in modeling femoral fracture in mice with zero expression of 11β-HSD2 (11β-HSD2-/-) or both 11β-HSD2 and apolipoprotein e (11β-HSD2-/-/ApoE-/-).
 Materials and Methods: The experimental study was conducted on 60 male mice weighing 24-30 g. The study used male mice that lacked the expression of 11β-HSD2 (knockout mice with the Hsd2-/- genotype) and male mice that lacked the expression of 11β-HSD2 and apolipoprotein E (double knockout mice with the Hsd2-/-/ApoE-/- genotype). The control group includes wild type C57bl/6 animals. Modeling of a fracture of the proximal metaphysis of the femur was performed in animals at the age of 6 months using a closed technique. Fracture fusion and bone remodeling and osteoreparation processes were evaluated 6 weeks after fracture modeling.
 Results and Discussion: It has been shown that a violation of the regulation of steroid hormone metabolism in groups of animals with the Hsd2-/- and Hsd2-/-/ApoE-/- genotypes leads to an increase in the number of ungrown fractures by 3 and 3.5 times, respectively, in comparison with wild-type animals. It was found that the microcirculation level of the proximal metaphysis of the left femur in the area of the formed bone callus in the group of animals with the genotype 11β-HSD2-/- significantly decreased from 92.075±4.33 perfusion units (PE) in the group of wild-type animals to 82.67±3.54 PE (p=0.0002) in the group of animals with the genotype HSD2-/- and up to 75.85±5.64 (p<0.0001) in the group of mice with the Hsd2-/-/ApoE-/- genotype. When calculating the coefficient of endothelial dysfunction, an increase in the coefficient of endothelial dysfunction was found from 1.297±0.19 in intact animals to 2.115±0.45 (p<0.00001) in the group of mice with the Hsd2-/- genotype and to 2.41±0.04 (p<0.00001) in the group of mice with the Hsd2-/-/ApoE-/- genotype. In animals with impaired cortisol metabolism, there was a slowdown in the formation of bone tissue in the fracture area, bone trabeculae had a smaller width, large amounts of fibrous and connective tissue were observed in the lumen between bone fragments, and an increase in intertrabecular spaces was noted
 Conclusion: The close relationship between the metabolism of 11β-HSD2 and NO, confirmed in this study, can be considered as a promising pharmacotherapeutic target. It is obvious that approaches to changing the activity of 11β-HSD have significant therapeutic potential in the treatment of osteoporosis, bone remodeling disorders and osteoreparation in fractures against the background of formed osteoporotic changes in the violation of steroid hormone metabolism.

Regulating Chondro-Bone Metabolism for Treatment of Osteoarthritis via High-Permeability Micro/Nano Hydrogel Microspheres.

Destruction of cartilage due to the abnormal remodeling of subchondral bone (SB) leads to osteoarthritis (OA), and restoring chondro-bone metabolic homeostasis is the key to the treatment of OA. However, traditional intra-articular injections for the treatment of OA cannot directly break through the cartilage barrier to reach SB. In this study, the hydrothermal method is used to synthesize ultra-small size (≈5nm) selenium-doped carbon quantum dots (Se-CQDs, SC), which conjugated with triphenylphosphine (TPP) to create TPP-Se-CQDs (SCT). Further, SCT is dynamically complexed with hyaluronic acid modified with aldehyde and methacrylic anhydride (AHAMA) to construct highly permeable micro/nano hydrogel microspheres (SCT@AHAMA) for restoring chondro-bone metabolic homeostasis. In vitro experiments confirmed that the selenium atoms scavenged reactive oxygen species (ROS) from the mitochondria of mononuclear macrophages, inhibited osteoclast differentiation and function, and suppressed early chondrocyte apoptosis to maintain a balance between cartilage matrix synthesis and catabolism. In vivo experiments further demonstrated that the delivery system inhibited osteoclastogenesis and H-vessel invasion, thereby regulating the initiation and process of abnormal bone remodeling and inhibiting cartilage degeneration in SB. In conclusion, the micro/nano hydrogel microspheres based on ultra-small quantum dots facilitate the efficient penetration of articular SB and regulate chondro-bone metabolism for OA treatment.

Dietary supplementation with nacre reduces cortical bone loss in aged female mice

Aging is associated with detrimental bone loss leading to fragility fractures in both men and women. Notably, a majority of bone loss with aging is cortical, as well as a large number of fractures are non-vertebral and at the non-hip sites. Nacre is a product of mollusks composed of calcium carbonate embedded in organic components. As our previous study demonstrated the protective effect of nacre supplementation on trabecular bone loss in ovariectomized rats, we sought to evaluate the effect of dietary nacre on bone loss related to aging in female mice which do not suffer true menopause as observed in women. The current study compared the effect of a 90-day long nacre-supplemented diet to that of Standard or CaCO3 diets on both bone mass and strength in 16-month-old C57BL/6 female mice. Multiple approaches were performed to assess the microarchitecture and mechanical properties of long bones, analyze trabecular histomorphometry, and measure bone cell-related gene expressions, and bone turnover markers. In the cortex, dietary nacre improved cortical bone strength in line with lower expression levels of genes reflecting osteoclasts activity compared to Standard or CaCO3 diets (p < 0.05). In the trabeculae, nacre-fed mice were characterized by a bone remodeling process more active than the other groups as shown by greater histomorphometric parameters and osteoblast-related gene expressions (p < 0.05). But these differences were not exhibited at the level of the trabecular microarchitecture at this age. Collectively, these data suggest that dietary nacre should be a potential candidate for reducing aging-associated cortical bone loss in the elderly.

Oncostatin M enhances osteoprotegerin synthesis but reduces macrophage colony‑stimulating factor synthesis in bFGF‑stimulated osteoblast‑like cells.

Bone remodeling is tightly controlled by various factors, including hormones, autacoids and cytokines. Among them, oncostatin M (OSM) is a multifunctional cytokine produced by osteal macrophages, which serves as an essential modulator of bone remodeling. Macrophage colony-stimulating factor (M-CSF) and osteoprotegerin are secreted by osteoblasts, and also have pivotal roles in the regulation of the bone remodeling process. The binding of basic fibroblast growth factor (bFGF), a key regulator of bone remodeling, to the corresponding receptor [fibroblast growth factor receptor (FGFR)] triggers the dimerization and activation of FGFRs, which causes the phosphorylation of FGFR substrates and subsequent activation of downstream effectors, including mitogen-activated protein kinases (MAPKs), via Grb2. bFGF can activate MAPKs, resulting in the synthesis of osteoprotegerin and vascular endothelial growth factor in osteoblast-like MC3T3-E1 cells. In the present study, the effects of OSM on bFGF-induced osteoblast activation were investigated in the synthesis of osteoprotegerin and M-CSF in osteoblasts. The release of osteoprotegerin and M-CSF were analyzed using ELISA. The mRNA expression levels of osteoprotegerin and M-CSF were analyzed using reverse transcription-quantitative PCR. Phosphorylation of p38 MAPK, stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p44/p42 MAPK was assessed using western blotting. OSM enhanced bFGF-induced osteoprotegerin release and bFGF-stimulated mRNA expression of osteoprotegerin. By contrast, OSM suppressed the bFGF-induced release of M-CSF and bFGF-stimulated mRNA expression of M-CSF. SB203580, a p38 MAPK inhibitor, and SP600125, a SAPK/JNK inhibitor, suppressed the bFGF-stimulated M-CSF release, whereas PD98059, an upstream kinase inhibitor of p44/p42 MAPK, failed to suppress the M-CSF release stimulated by bFGF. Furthermore, OSM enhanced the bFGF-induced phosphorylation of p38 MAPK, but attenuated the bFGF-stimulated phosphorylation of SAPK/JNK. By contrast, OSM had little effect on the bFGF-induced phosphorylation of p44/p42 MAPK. SB203580 markedly reduced the amplification of bFGF-stimulated osteoprotegerin release enhanced by OSM. These results strongly suggested that OSM may possess divergent effects on bFGF-induced osteoblast activation, upregulation of p38 MAPK and downregulation of SAPK/JNK, leading to the amplification of osteoprotegerin synthesis and the attenuation of M-CSF synthesis.

Impact of Mechanical Strain and Nicotinamide on RUNX2-Deficient Osteoblast Mimicking Cleidocranial Dysplasia

Cleidocranial dysplasia (CCD) is a rare genetic defect caused by a heterozygous mutation of runt-related transcription factor 2 (RUNX2), which is important for osteoblast and skeletal development. RUNX2-deficiency causes extra- and intra-oral malformations that often require orthodontic treatment. Nicotinamide (NAM) affects bone remodelling processes. As these are crucial for orthodontic therapy, NAM could improve orthodontic treatment in CCD patients. This study investigates the effect of NAM in control and RUNX2-deficient osteoblasts under mechanical strain mimicking orthodontic treatment. First, the optimal NAM concentration and the differences in the expression profile of control and RUNX2-deficient osteoblasts were determined. Subsequently, osteoblasts were exposed to tensile and compressive strain with and without NAM, and the expression of genes critically involved in bone remodelling was investigated. NAM increased the expression of bone remodelling genes. RUNX2-deficient osteoblasts expressed more receptor activator of NFkB ligand (RANKL) and interleukin-6 (IL6), but less colony-stimulating factor-1 (CSF1). Most of the positive effects of NAM on bone remodelling genes were impaired by mechanical loading. In conclusion, NAM stimulated osteoblast differentiation by increasing the expression of RUNX2 and regulated the expression of osteoclastogenic factors. However, the positive effects of NAM on bone metabolism were impaired by mechanical loading and RUNX2 deficiency.

CEGAH OSTEOPOROSIS MELALUI PELATIHAN SENAM LANSIA DAN CERAMAH KESEHATAN DI DESA TANJUNG GUSTA

Osteoporosis is a systemic bone disorder, which is characterized by damage to the micro-architecture of bone tissue, which occurs as a result of an imbalance in the bone remodeling process. Various actions that can be taken to prevent osteoporosis one of which is to increase physical activity such as exercise. Exercise can stimulate bone growth and maintain bone mass. The series of activities carried out were training in elderly gymnastics at the beginning of the event, then followed by providing counseling about Osteoporosis using the health lecture method. The purpose of this activity was to provide education about osteoporosis and to train elderly gymnastic movements as a step to prevent osteoporosis. This activity was attended by 30 participants in Dusun II Timur, Tanjung Gusta Village, all of whom were female. The results of this activity showed that as many as 22 people (73.3%) participants showed an increase in test results, and the results of the paired t test showed a significant difference between the pretest and posttest results with a p value &lt;0.05, meaning that this activity was effective in terms of increasing knowledge about Osteoporosis in all participants

In Vitro and In Vivo Bone-Forming Effect of a Low-Molecular-Weight Collagen Peptide.

This study reveals that low-molecular-weight collagen peptide (LMWCP) can stimulate the differentiation and the mineralization of MC3T3-E1 cells in vitro and attenuate the bone remodeling process in ovariectomized (OVX) Sprague-Dawley rats in vivo. Moreover, the assessed LMWCP increased the activity of alkaline phosphatase (ALP), synthesis of collagen, and mineralization in MC3T3-E1 cells. Additionally, mRNA levels of bone metabolism-related factors such as the collagen type I alpha 1 chain, osteocalcin (OCN), osterix, bone sialoprotein, and the Runt family-associated transcription factor 2 were increased in cells treated with 1,000 μg/ml of LMWCP. Furthermore, we demonstrated that critical bone morphometric parameters exhibited significant differences between the LMWCP (400 mg/kg)-receiving and vehicle-treated rat groups. Moreover, the expression of type I collagen and the activity of ALP were found to be higher in both the femur and lumbar vertebrae of OVX rats treated with LMWCP. Finally, the administration of LMWCP managed to alleviate osteogenic parameters such as the ALP activity and the levels of the bone alkaline phosphatase, the OCN, and the procollagen type 1 N-terminal propeptide in OVX rats. Thus, our findings suggest that LMWCP is a promising candidate for the development of food-based prevention strategies against osteoporosis.

Periodontal ligament and alveolar bone remodeling during long orthodontic tooth movement analyzed by a novel user-independent 3D-methodology

The structural process of bone and periodontal ligament (PDL) remodeling during long-term orthodontic tooth movement (OTM) has not been satisfactorily described yet. Although the mechanism of bone changes in the directly affected alveolar bone has been deeply investigated, detailed knowledge about specific mechanism of PDL remodeling and its interaction with alveolar bone during OTM is missing. This work aims to provide an accurate and user-independent analysis of the alveolar bone and PDL remodeling following a prolonged OTM treatment in mice. Orthodontic forces were applied using a Ni–Ti coil-spring in a split-mouth mice model. After 5 weeks both sides of maxillae were scanned by high-resolution micro-CT. Following a precise tooth movement estimation, an extensive 3D analysis of the alveolar bone adjacent to the first molar were performed to estimate the morphological and compositional parameters. Additionally, changes of PDL were characterized by using a novel 3D model approach. Bone loss and thinning, higher connectivity as well as lower bone mineral density were found in both studied regions. Also, a non-uniformly widened PDL with increased thickness was observed. The extended and novel methodology in this study provides a comprehensive insight about the alveolar bone and PDL remodeling process after a long-duration OTM.

Chemotherapy and adjuvant therapies' impact on the internal remodeling process of bone and its mechanical behavior for breast cancer patients.

Breast cancer is a significant public health issue affecting women worldwide. While advancements in treatment options have led to improved survival rates, the impact of breast cancer and its treatments on bone health cannot be overlooked. Bone remodeling is a complex process regulated by the delicate balance between bone formation and resorption. Any disruption to this balance can lead to decreased bone density, increased fracture risk, and compromised physical function. To investigate the effects of breast cancer and its treatments on bone remodeling, a finite element model was developed in this study. This model incorporated bone remodeling equations to simulate the mechanical behavior of bone under different conditions. The ABAQUS/UMAT software was used to simulate the behavior of bone tissue under the influence of breast cancer and treatments. Our findings suggest that bone loss is more pronounced after secondary breast cancer and treatment, leading to bone loss (6%-19% decrease in BV/TV), reduced bone stimulation, and decreased effectiveness of physical activity on recovery. These results highlight the importance of early intervention and management of bone health in breast cancer patients to mitigate the negative impact of cancer and treatment on bone remodeling.

Research Progress of Titanium-Based Alloys for Medical Devices.

Biomaterials are currently a unique class of materials that are essential to improving the standard of human life and extending it. In the assent of the appearance of biomaterials that contain non-toxic elements, in this study, we examine a system of Ti25Mo7Zr15TaxSi (x = 0, 0.5, 0.75, 1 wt.%) for future medical applications. The alloys were developed in a vacuum electric arc furnace and then studied from a structural, mechanical and in vivo assessment (on rabbits) perspective. The effect of the silicon addition was clearly seen in both the structural and the mechanical characteristics, standing out as beta alloys with a dendritic structure and lowering the mechanical properties as a result of the silicon addition. In experimental rabbits, the proliferation of mesenchymal stem cells was observed in the periosteum and peri-implant area, differentiating into osteoblasts and then into osteocytes. Osteoclasts were discovered within the cartilaginous islands that provide structural support to newly formed bone, playing a primary role in bone remodeling. The newly formed spongy tissue adhered to the fibrous capsule that surrounds the alloy, ensuring good osseointegration of metallic implants. The overexpression of Osteopontin, Metalloproteinase-2 (also known as gelatinase A), and Metallopeptidase-9 (also known as gelatinase B) underscores the processes of osteogenesis, bone mineralization, and normal bone remodeling.

Effects of glass-ceramic produced by the sol-gel route in macrophages recruitment and polarization into bone tissue regeneration.

Effective bone substitute biomaterials remain an important challenge in patients with large bone defects. Glass ceramics produced by different synthesis routes may result in changes in the material physicochemical properties and consequently affect the success or failure of the bone healing response. To investigate the differences in the orchestration of the inflammatory and healing process in bone grafting and repair using different glass-ceramic routes production. Thirty male Wistar rats underwent surgical unilateral parietal defects filled with silicate glass-ceramic produced by distinct routes: BS - particulate glass-ceramic produced via the fusion/solidification route, and BG - particulate glass-ceramic produced via the sol-gel route. After 7, 14, and 21 days from biomaterial grafting, parietal bones were removed to be analyzed under H&E and Massons' Trichome staining, and immunohistochemistry for CD206, iNOS, and TGF-β. Our findings demonstrated that the density of lymphocytes and plasma cells was significantly higher in the BS group at 45, and 7 days compared to the BG group, respectively. Furthermore, a significant increase of foreign body giant cells (FBGCs) in the BG group at day 7, compared to BS was found, demonstrating early efficient recruitment of FBGCs against sol-gel-derived glass-ceramic particulate (BS group). According to macrophage profiles, CD206+ macrophages enhanced at the final periods of both groups, being significantly higher at 45 days of BS compared to the BG group. On the other hand, the density of transformation growth factor beta (TGF-β) positive cells on 21 days were the highest in BG, and the lowest in the BS group, demonstrating a differential synergy among groups. Noteworthy, TGF-β+ cells were significantly higher at 21 days of BG compared to the BS group. Glass-ceramic biomaterials can act differently in the biological process of bone remodeling due to their route production, being the sol-gel route more efficient to activate M2 macrophages and specific FBGCs compared to the traditional route. Altogether, these features lead to a better understanding of the effectiveness of inflammatory response for biomaterial degradation and provide new insights for further preclinical and clinical studies involved in bone healing.

Age estimation in the combined long bones and ribs by histomorphometry: Past, present, and future.

Numerous age estimation methods in unidentified bone have been a long time developing for application in forensic anthropology. The histomorphometric technique is one of the alternative methods that relied upon the evaluation of the cortical bone microstructure over the lifespan as a result of the remodeling process in bone. Remodeling is a sophisticated event occurring from the coupled function of bone formation and resorption cells for maintaining mineral homeostasis and repairment of microdamage in bone tissue. Products derived from remodeling are primary changes in the osteon or haversian system in various regions in the cortical bone, including periosteum, endosteum, and trabecular bone. Throughout life, bone remodeling rate with osteon alteration can be predictable. In the forensic field, histological methods are getting more attention due to the unavailability of macroscopic methods. Histomorphometry approach can be accomplished in fragmentary or incomplete bone remains indicating the limited use of gross morphological methods. In addition, the microscopic methods can aid to increase the more accuracy of analyses and diminish the biased subjective assessment for determining age. Most histomorphometry method utilizes a cross-section of the midshaft of the long bones including the mandible, rib, and clavicle. This review provides the basic knowledge of bone biology and anatomy, several age-estimating methods of histology, and crucial factors for age methods. Studies regarding overall age determination methods from the past until now contribute to obtaining more benefits for developing methods of histomorphometry using human bone in forensic identification.

Histological Comparison of Collagenated Cancellous Equine Bone Blocks Used as Inlay or Onlay for Lateral Bone Augmentation in Rabbits.

The conformation of the recipient site for an inlay graft presents an increased contact with the parent bone compared to an onlay graft. This might favor bone growth within the inlay compared to onlay grafts. Hence, the objective of this study was to compare the bone incorporation and remodeling processes of xenogeneic en bloc grafts placed using two bone grafting techniques, i.e., onlay vs. inlay. In this prospective, randomized, split-mouth study (test and control sides in the same animal), two bone grafting techniques were comparatively evaluated. The lateral aspect of the rabbit mandible was used as the recipient site, bilaterally. On one side of the mandible, the cortical bone was perforated with drills to allow a better bone formation from the bone wound and the marrow spaces. A xenogeneic bone block was fixed in the center of the prepared region, representing the onlay site. On the other side of the mandible, a 7 mm wide and 3 mm deep circumferential defect was prepared using trephines and drills. A xenogeneic bone block was fixed in the center of the defect, representing the inlay site. Two healing periods were applied in the study: 2 and 10 weeks, each represented by 10 rabbits (n = 10 for each period). After 2 weeks of healing, the mean percentage of new bone was 10.4% and 23.3% at the onlay and inlay grafts, respectively (p = 0.022). After 10 weeks of healing, new bone increased to 13.2% at the onlay sites and 25.4% at the inlay sites (p = 0.080). In the 10-week period, the inlay grafts presented a homogeneous growth of new bone in all regions, while in the onlay grafts, low percentages of new bone were observed in the external regions. The percentage of new bone increased faster and was higher in the inlay grafts than in the onlay grafts. This outcome might be related to the self-contained conformation of the recipient site in the inlay group, which offered more sources for new bone formation compared to the one-wall conformation of the recipient sites in the onlay group. The osteoconductive properties of the biomaterial allowed the newly formed bone to reach the most peripheral regions in both groups. The osteoconductive properties of the biomaterial, together with the protection offered by the collagen membrane, allowed marginal closure of the defects by newly formed bone in the inlay group.

Bone Remodeling Process and Covid-19: A Modelling Approach

Apart from the effects on the lungs, COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) also has effects on bone metabolism including the bone remodelling process. The bone remodelling process involves bone formation by bone-forming cells (osteoblasts) and bone resorption by bone-resorbing cells (osteoclasts). The infection with SARS-Cov-2 decreases the inhibiting effects of Angiotensin-converting enzyme 2 (ACE2) on osteoclastic reproduction and inhibits the osteogenic ability of osteoblasts which might lead to the imbalance in the bone remodeling process. In this study, we modify the system of differential equations to investigate the effects of Covid-19 on bone formation and bone resorption. The geometric singular perturbation method is utilized to analyze the modified model theoretically. To illustrate the theoretical results, numerical investigations are also demonstrated. The results indicate that the oscillations in the numbers of osteoclastic cells and osteoblastic cells observed in the clinical evidence could still be expected when the effects of SARS-Cov-2 are incorporated, however, the oscillations occur at the higher level of the number of osteoclasts and hence more bone loss might occur when infected with Covid-19.

Deciphering the Cell-Specific Effect of Osteoblast-Macrophage Crosstalk in Periodontitis.

In periodontitis, the bone remodeling process is disrupted by the prevalent involvement of bacteria-induced proinflammatory macrophage cells and their interaction with osteoblast cells residing within the infected bone tissue. The complex interaction between the cells needs to be deciphered to understand the dominant player in tipping the balance from osteogenesis to osteoclastogenesis. Yet, only a few studies have examined the crosstalk interaction between osteoblasts and macrophages using biomimetic three-dimensional (3D) tissue-like matrices. In this study, we created a cell-laden 3D tissue analog to study indirect crosstalk between these two cell types and their direct synergistic effect when cultured on a 3D scaffold. The cell-specific role of osteoclast differentiation was investigated through osteoblast- and proinflammatory macrophage-specific feedback studies. The results suggested that when macrophages were exposed to osteoblasts-derived conditioned media from the mineralized matrix, the M1 macrophages tended to maintain their proinflammatory phenotype. Further, when osteoblasts were exposed to secretions from proinflammatory macrophages, they demonstrated elevated receptor activator of nuclear factor-κB ligand (RANKL) expression and decreased alkaline phosphate (ALP) activities compared to osteoblasts exposed to only osteogenic media. In addition, the upregulation of tumor necrosis factor-alpha (TNF-α) and c-Fos in proinflammatory macrophages within the 3D matrix indirectly increased the RANKL expression and reduced the ALP activity of osteoblasts, promoting osteoclastogenesis. The contact coculturing with osteoblast and proinflammatory macrophages within the 3D matrix demonstrated that the proinflammatory markers (TNF-α and interleukin-1β) expressions were upregulated. In contrast, anti-inflammatory markers (c-c motif chemokine ligand 18 [CCL18]) were downregulated, and osteoclastogenic markers (TNF receptor associated factor 6 [TRAF6] and acid phosphatase 5, tartrate resistant [ACP5]) were unchanged. The data suggested that the osteoblasts curbed the osteoclastogenic differentiation of macrophages while macrophages still preserved their proinflammatory lineages. The osteoblast within the 3D coculture demonstrated increased ALP activity and did not express RANKL significantly different than the osteoblast cultured within a 3D collagen matrix without macrophages. Contact coculturing has an anabolic effect on bone tissue in a bacteria-derived inflammatory environment.