Bone Absorption Research Articles

Controlled delivery of procyanidin through magnesium oxide nanoparticles (MgO NPs) to improve the activity and mineralization of osteoblasts under oxidative stress in vitro

Excessive reactive oxygen species (ROS) in the microenvironment of osteoporosis (OP) not only accelerate the bone absorption, but also affect the osteogenic and mineralized effect of osteoblasts. Procyanidins (PC) have been reported to have anti-oxidation effects, but low bioavailability. This study aimed to explore the effect of magnesium oxide nanoparticles (MgO-PC NPs)-loaded PC on the osteogenesis and mineralization of osteoblasts that stimulated by H2O2. PC was loaded onto MgO NPs and characterized by transmission electron microscopy, energy dispersive spectroscopy, dynamic light scattering, and Fourier transform infrared spectroscopy. After primary screening by cytotoxicity assay, MgO-PC NPs containing 20 μM of PC were chosen for further studies. In H2O2-stimulated osteoblasts, dichlorodihydrofluorescein diacetate probe, Cell Counting Kit-8, quantitative real-time polymerase chain reaction, alkaline phosphatase staining/activity and Alizarin red staining were used to detect the ROS production, cell viability and osteogenic and mineralized markers of osteoblasts. PC was loaded onto MgO NPs to successfully receive MgO-PC NPs with a diameter of about 144 nm and negative potential. PC can sustain release from MgO-PC NPs for at least 16 d. The controlled release of PC from MgO-PC NPs can effectively eliminate ROS and thereby promoted the cell activity. Most importantly, the osteogenesis and mineralization of osteoblasts under oxidative stress were also significantly reversed by MgO-PC NPS. Thus, these findings indicate that MgO-PC NPs may be developed as a potential therapeutic strategy for OP.

Comprehensive three-dimensional cone beam computed tomography assessment unilateral alveolar cleft reconstruction using autologous iliac cancellous bone combined with deproteinized bovine bone: A clinical retrospective evaluation

Large-volume autologous iliac cancellous bone grafting for alveolar cleft may lead to undesirable bone resorption and susceptible donor-site morbidity, whereas the addition of deproteinized bovine bone (DBB) could optimize outcomes. This study aimed to evaluate the effectiveness of combining autologous iliac bone with DBB using three-dimensional cone beam computed tomography (3D-CBCT) for better analysis of bone generation than conventional evaluation methods. Thirty-six patients with unilateral alveolar cleft were assigned into two groups. Group A (n = 21) underwent autogenous cancellous bone graft harvested from the anterior iliac crests, while Group B (n = 15) received a composite of autogenous iliac cancellous bone and DBB. Patients in Group B displayed higher bone filling rates (P < 0.0001) and lower bone absorption rates (P < 0.001) than those in Group A at both 6 months and 1 year postoperatively. Additionally, there were directional differences in bone absorption within the bone grafts, with more absorption observed on the alveolar crest and palatal sides than that on the nasal and labial sides (P < 0.001). This study demonstrates that employing a combination of DBB and autologous bone in alveolar cleft repair achieves better outcomes of bone grafting.

Role of connexin 43 in a rat model of periodontitis-induced renal injury.

This study aims to investigate the role of gap junction mediated by connexin 43 (Cx43) in renal injury induced by periodontitis in rats. Twelve SPF-grade Wistar male rats were divided into a control group and a periodontitis group by using a completely random number table method, with six rats in each group. The control group rats were not treated, while the periodontitis group rats were subjected to wire ligation of the neck of their bilateral maxillary first molars to construct a periodontitis model. After 8 weeks of modeling, the rats were examined for clinical indicators of the periodontium. micro-CT scanning of the maxilla reconstructed its 3D structure and analyzed the absorption of alveolar bone. Histopathological changes in periodontal and renal tissues were detected. MitoSOX red reagent was used to determine reactive oxygen species (ROS) content in renal tissues. A biochemical reagent kit was used to detect serum oxidative stress biomarkers. Real-time fluorescent quantitative-polymerase chain reaction (qRT-PCR) was employed to determine Cx43, nuclear factor kappa-B (NF-κB) , interleukin (IL)-1β, IL-6, BCL2-Associated X (Bax), B-lymphomatoma-2 gene (Bcl-2), and Caspase-3 mRNA were determined. Western blot analysis was used to detect Cx43, NF-κB, IL-1β, Bax, Bcl-2 and Caspase-3 protein. micro-CT 3D reconstruction showed significant bone resorption of the first molar alveolar bone in the periodontitis group rats and decreased height of the alveolar ridge. The distance from the enamel cementum boundary to the top of the alveolar ridge in the periodontitis group was significantly higher than that inthe control group. The histopathological results showed a large number of inflammatory cells that infiltrated the periodontal tissue of the periodontitis group, and the alveolar bone was significantly absorbed. Rats in the periodontitis group also exhibited mild thickening of the glomerular basement membrane, dilation of the Bowman's capsule, and destruction of the brush-like edge of the renal tubules in the renal tissue. The MitoSOX red staining results showed a significant increase in ROS content in the renal tissue of the periodontitis group. The biochemical test results showed that the levels of superoxide dismutase and glutathione in the serum of rats with periodontitis decreased, while that of malondialdehyde increased. The results of qRT-PCR and Western blot showed that the expression levels of Cx43, IL-1β, IL-6, Bax, Caspase-3 mRNA and Cx43, IL-1β, NF-κB, Bax, Caspase-3 proteins in the periodontitis group significantly increased compared with those in the control group, while the expression levels of Bcl-2 mRNA and protein decreased. Periodontitis may activate NF-κB signaling molecules by upregulating the expression of Cx43 in rat kidney tissues, leading to increased levels of inflammation and apoptosis and ultimately inducing kidney injury.

Chaperone-mediated autophagy protects the bone formation from excessive inflammation through PI3K/AKT/GSK3β/β-catenin pathway.

Multiple regulatory mechanisms are in place to ensure the normal processes of bone metabolism, encompassing both bone formation and absorption. This study has identified chaperone-mediated autophagy (CMA) as a critical regulator that safeguards bone formation from the detrimental effects of excessive inflammation. By silencing LAMP2A or HSCA8, we observed a hindrance in the osteoblast differentiation of human bone marrow mesenchymal stem cells (hBMSCs) invitro. To further elucidate the role of LAMP2A, we generated LAMP2A gene knockdown and overexpression of mouse BMSCs (mBMSCs) using adenovirus. Our results showed that LAMP2A knockdown led to a decrease in osteogenic-specific proteins, while LAMP2A overexpression favored the osteogenesis of mBMSCs. Notably, active-β-catenin levels were upregulated by LAMP2A overexpression. Furthermore, we found that LAMP2A overexpression effectively protected the osteogenesis of mBMSCs from TNF-α, through the PI3K/AKT/GSK3β/β-catenin pathway. Additionally, LAMP2A overexpression significantly inhibited osteoclast hyperactivity induced by TNF-α. Finally, in a murine bone defect model, we demonstrated that controlled release of LAMP2A overexpression adenovirus by alginate sodium capsule efficiently protected bone healing from inflammation, as confirmed by imaging and histological analyses. Collectively, our findings suggest that enhancing CMA has the potential to safeguard bone formation while mitigating hyperactivity in bone absorption.

Synovial osteoclastogenesis mediated by chondrocyte-secreted TNFα promotes TMJ condylar resorption.

Insufficient occlusal support (IOS) frequently causes subchondral bone absorption in temporomandibular joint osteoarthritis, and the underlying mechanism requires further investigation. An IOS model was established by abrading rat molars. Micro-computed tomography was used to evaluate subchondral bone changes. Osteoclastogenesis of synovium-derived macrophages (SDMs) was confirmed by TRAP staining. Cartilage-specific TNFα depletion was achieved by intra-articular injection of adeno-associated virus carrying shRNA against murine TNFα under control of collagen type II. Invitro, chondrocytes were mechanically compressed and conditioned medium (CM) was collected to detect its ability to induce osteoclastogenesis of SDMs. Synovial osteoclastogenesis and condyle resorption were observed following IOS. TNFα level was elevated in hypertrophic chondrocytes after IOS. Synovial Wnt5a level increased, but Wnt3a level decreased after IOS. Depletion of TNFα in chondrocytes alleviated the synovial osteoclastogenesis and condyle bone resorption. Invitro compression of chondrocytes potentiated TNFα expression and secretion. The CM promoted osteoclastogenesis of SDMs, which were partially prohibited by TNFα neutralizing antibody. Furthermore, inhibition of Wnt3a facilitated osteoclastogenesis, whereas inhibition of Wnt5a partially suppressed osteoclastogenesis, of SDMs cultured in CM. Chondrocyte-secreted TNFα induced by IOS is a critical regulator of synovial osteoclastogenesis and subsequent condylar resorption, partially through non-canonical Wnt5a pathway.

P079 Denosumab treatment for bone marrow oedema - a case series

Abstract Background/Aims This is a case series of patients treated with a single dose of denosumab to improve bone marrow oedema. Bone marrow oedema can cause significant pain and functional limitations. On MRI imaging, bone marrow oedema is identified as T1 hypointensities and T2 hyperintensities. Denosumab is a human monoclonal antibody that inhibits osteoclast bone absorption via binding to the cytokine RANKL [receptor activator of nuclear factor kappa-B ligand]. The exact aetiology of bone marrow oedema is unknown. It typically occurs in those aged between 40 to 60 years old. Studies have described therapeutic improvement with antiresorptive medications. Bone marrow oedema will generally resolve if left untreated. However, pharmacological treatments can curtail the clinical course. Methods This case series has emerged from Chelsea and Westminster hospital. Data was collected over a five year period for seven patients with bone marrow oedema [demonstrated on MRI] that were treated with denosumab. Six of the seven patients had a spontaneous insufficiency fracture associated with the bone marrow oedema on imaging. In our case series, two of the patients had bone marrow oedema in their hips and five in their knees. Denosumab was administered as a single 60mg subcutaneous injection. Response to treatment was ascertained by repeat MRI scan 2-4 months after denosumab treatment as well as patient reported outcomes. Results The average age of the patients was 56.4 years [age range 48-68 years]. Five of the patients [71%] reported improved symptoms at the affected site. Four patients [57%] had complete resolution of their bone marrow oedema on imaging with a further patient [14%] having an improved radiological appearance. Visual analogue scale [VAS] scores improved by 50%, although this data was only collected for some of the patients. No side-effects or complications were noted from the treatment. One of the patients who did not improve with denosumab treatment went on to have a total hip replacement due to complete loss of joint space. It is noteworthy that following further investigations, five of the seven patients were diagnosed with osteopenia on dual-energy x-ray absorptiometry [DEXA] scan, one had osteoporosis [and was subsequently commenced on alendronic acid] and one did not attend for their DEXA scan. Conclusion This series demonstrates that denosumab is an effective treatment for bone marrow oedema. Denosumab given as a single dose can be considered a safe treatment; there is not the risk of rebound worsening of bone density on treatment cessation that can be seen with prolonged treatment. Denosumab should be offered to patients who are symptomatic from bone marrow oedema to allow for quicker symptom relief and radiological improvement. Our findings are similar to that of a slightly larger case series of fourteen patients by Rolvien et al. published in 2017. Disclosure M. Galloway: None. A. Jacobs: None. M. Ismajli: None.

Development of porous hydroxyapatite/PVA/gelatin/alginate hybrid flexible scaffolds with improved mechanical properties for bone tissue engineering

Porous scaffolds based on gelatin and hydroxyapatite particles (HAp) are promising for applications in bone tissue engineering and regenerative medicine. However, they are not ideal for stress and shock protection due to low compressive strength, brittleness, and poor toughness. Herein, we developed porous hybrid scaffolds by combining multiple components into a single bone scaffold, including hydroxyapatite nanoparticles (HAp NPs), alginate, polyvinyl alcohol (PVA), and gelatin with different gelatin/PVA composition ratios. HAp NPs were synthesized in situ in PVA solution and scaffolds were fabricated using a freeze-drying method. The results showed good physicochemical properties of the scaffolds: formation of pure HAp NPs phase, high porosity, large pore sizes, large swelling capacity depending on varying gelatin/PVA ratios, as well as a long-term degradation rate up to 28 days. The porous scaffolds exhibited compressive strength close to the cancellous bone with stress-strain behavior exhibiting three-stage flexible behavior indicating improved fracture resistance with an energy absorbing capability up to 1.9 MJ/m3. The scaffolds have a yield strength of 70–403 kPa, a compressive strength at 65 % strain of 0.96–1.80 MPa, a nonporous elastic modulus of 10.44–12.40 GPa, and a densification strain of approximately 0.92 %. This work develops three-dimensional (3D) porous hybrid bone scaffolds with mechanical strength within the minimum compressive strength of cancellous bone and mechanical energy absorption capacity favor for cancellous bone repair, bone tissue engineering, and regenerative medicine applications.

Bone graft absorption complication following cranioplasty: A retrospective institutional study.

The aim of the present retrospective study was to confer the factors that are related to bone graft absorption and affect the outcomes of patients following cranioplasty (CPL). The present retrospective study includes cases of patients that underwent CPL between February, 2013 and December, 2022. All participants had a follow-up period of 1 to 10 years from the day of discharge from the hospital. In total, 116 (62.3%) of the 186 patients that underwent decompressive craniectomy (DC) were enrolled in the present study for CPL. A total of 109 (93.9%) patients were included in group A, and 7 (6.0%) patients were included in group B. On the whole, the results of the present study suggest that a CPL after 2.5-7.7 months of DC increases the possibility of bone absorption.

Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells.

The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years, which also may lead to some complications such as alveolar bone resorption or tooth root resorption. Low-intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, has been shown to promote bone fracture healing. It is also reported that LIPUS could reduce the duration of orthodontic treatment; however, how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear. To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement (OTM) model and explore the underlying mechanisms. A rat model of OTM was established, and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections. In vitro, human bone marrow mesenchymal stem cells (hBMSCs) were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction, Western blot, alkaline phosphatase (ALP) staining, and Alizarin red staining. The expression of Yes-associated protein (YAP1), the actin cytoskeleton, and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA (siRNA) application via immunofluorescence. The force treatment inhibited the osteogenic differentiation potential of hBMSCs; moreover, the expression of osteogenesis markers, such as type 1 collagen (COL1), runt-related transcription factor 2, ALP, and osteocalcin (OCN), decreased. LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force. Mechanically, the expression of LaminA/C, F-actin, and YAP1 was downregulated after force treatment, which could be rescued by LIPUS. Moreover, the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment. Consistently, LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo. The decreased expression of COL1, OCN, and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS. LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis, which may be a promising strategy to reduce the orthodontic treatment process.

Discordant responses of bone formation and absorption markers in Japanese infants with vitamin D deficiency: a comprehensive matched case-control study.

Vitamin D deficiency during infancy has been associated with increased bone turnover rate and bone mineral loss. However, few studies have examined bone turnover markers (BTMs) for both bone formation and resorption in infants with vitamin D deficiency. Here, we analyzed serum concentrations of 25OHD, intact parathormone (iPTH), and BTMs including total alkaline phosphatase (ALP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), and serum type I collagen N-telopeptide (NTx) as well as basic clinical characteristics of 456 infants (626 samples) aged less than 12mo born at Saitama City Hospital, Japan (latitude 35.9° North) between January 2021 and December 2022. One hundred sixteen infants (147 samples) were classified as having vitamin D deficiency (25OHD < 12.0ng/mL), and 340 infants (479 samples) had sufficient vitamin D levels (25OHD ≥ 12.0ng/mL). In addition to 25OHD and ALP, both TRACP-5b and sNTx were measured in 331 infants (418 samples), while 90 infants (105 samples) had only TRACP-5b measured and 101 infants (103 samples) had only sNTx measured. Statistical comparison of 104 subjects each in the vitamin D deficiency and sufficiency groups after matching for the background characteristics revealed that the vitamin D deficiency group had significantly higher levels of ALP and iPTH compared with the sufficiency group (P = <.0001, .0012, respectively). However, no significant differences were found in TRACP-5b and NTx levels between the 2 groups (P = .19, .08, respectively). Our findings suggest discordant responses between bone formation and resorption markers in subclinical vitamin D deficiency during infancy.

Clinical outcomes of reposition flap transfer for fingertip amputation.

This study aimed to describe the reposition flap for reconstructing fingertip amputation when replantation is not possible. This study retrospectively reviewed the records of patients with reposition flap transfers and investigated postoperative clinical outcomes and patient satisfaction. Sixteen patients with fingertip amputations treated with a reposition flap from 2016 to 2020. The mean age at injury was 46years (range, 26-70years). Ten cases were treated with oblique triangular advancement flaps, 3 with retrograde-flow digital artery flaps, and 3 with thumb palmar advancement flaps. Postoperative outcomes, including wound healing period and the IP/PIP extension angle, and the presence of grafted bone absorption and patient satisfaction were evaluated as of 3years after surgery. The average reduction in passive extension angle of the IP/PIP joint was 19°. The average time for complete wound healing was 28days (range, 18-41days). The reduction in passive extension angle of the IP/PIP joint was significantly correlated with the wound healing period (r = 0.66, p = 0.01). The absorption of the grafted bone was observed in 3 cases. In these cases, the distal tip of the flap became thin due to flap retraction and an insufficient flap volume. All patients were highly or fairly satisfied with the results of surgery. Our findings show that IP/PIP flexion contracture can occur due to delayed wound healing after reposition flap transfer, but the patient satisfaction level was generally high. Therefore, reconstruction using a reposition flap gives acceptable clinical outcomes and high patient satisfaction as a result of medium to long-term.

Major clinical outcomes of the use of biostimulators (L-PRF and coenzyme Q10) in the optimization of buccomaxillofacial surgery: a systematic review

Introduction: Tissue engineering combines three key elements matrix (three-dimensional structures that support growth, collagen cell, bone mineral), signaling molecules (growth factors (GF) and leukocyte cytokines), and cells (osteoblasts, fibroblasts or other adequate populations for tissue regeneration. Many studies suggest that antioxidants act as inhibitors of osteoclastogenesis and the inhibitory effect of CoQ10 on osteoclast differentiation. These findings highlight the potential therapeutic applications of CoQ10 for the treatment of bone diseases. Objective: The present study highlighted the main approaches to the use of fibrin-rich plasma (L-PRF) and coenzyme Q10 in buccomaxillofacial surgery through a systematic review. Methods: The systematic review rules of the PRISMA Platform were followed. The search was carried out from October 2023 to January 2024 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases, using articles from 2006 to 2022. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed accordingly, according to the Cochrane instrument. Results and Conclusion: A total of 104 articles were found, 38 articles were evaluated and 23 were included and developed in this systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 36 studies with a high risk of bias and 20 studies that did not meet GRADE. The use of platelet and leukocyte-rich fibrin can reduce bone absorption, infection, pain, local edema, and wound healing. L-PRF presents itself as an autogenous biomaterial with great versatility, low cost, easy acquisition and wide use, and infinite possibilities. It can be combined with other materials in the most diverse areas of dentistry. Also, CoQ10 concentrations can suppress ROS, which is needed as a signaling intermediate. CoQ10 acts as an enhancer of all stages of osteoblastic differentiation. Thus, CoQ10 suppresses osteoclast differentiation by eliminating generated intracellular ROS. Furthermore, CoQ10 enhances bone regeneration in all differentiation processes through transcription factor activity.

Regulatory signaling pathways of osteoblast autophagy in periprosthetic osteolysis

Periprosthetic osteolysis is a difficult-to-treat complication of arthroplasty. The pathological mechanisms of periprosthetic osteolysis are mainly weakened function of osteoblasts and excessive activation of osteoclasts. Many studies have demonstrated that the imbalance between the formation of bone by osteoblasts and the absorption of bone by osteoclasts is the direct cause of osteolytic diseases. Autophagy, as an important self-protective cellular mechanism, has significant effects on the regulation of osteoblast function, such as osteoblast differentiation, proliferation, and apoptosis. Osteoblasts, which play an important role in maintaining bone homeostasis, have attracted increasing attention in recent years. Up till now, Several signaling pathways have been proved to regulate autophagy of osteoblasts, including the AMPK, NF-κB, FoxO3 and other signaling pathways. This article reviews the recent progress in understanding osteoblast autophagy and mitophagy in the context of periprosthetic osteolysis and the signaling pathways which are involved in these processes. By summarizing previous studies describing the mechanism underlying osteoblast autophagy, we wish to contribute new therapeutic ideas and potential therapeutic targets for periprosthetic osteolysis.

Mechanism and physical activities in bone-skeletal muscle crosstalk.

Bone and skeletal muscle work in coordination to maintain the function of the musculoskeletal system, in which skeletal muscle contraction drives the movement of the bone lever system while bone provides insert sites for skeletal muscle through the bone-muscle junction. Existing evidence suggests that factors secreted by skeletal muscle and bone mediate the interaction between the two tissues. Herein, we focused on the relationship between skeletal muscle and bone and the underlying mechanism of the interaction. Exercise can promote bone strength and secrete osteocalcin and insulin-like growth factor I into the blood, thus improving muscle quality. In addition, exercise can also promote myostatin, interleukin-6, Irisin, and apelin in muscles to enter the blood so that they can act on bones to maintain the balance between bone absorption and bone formation. There is a special regulatory axis interleukin-6/osteocalcin between myokines and osteokines, which is mainly influenced by exercise. Therefore, we pay attention to the important factors in the bone-muscle intersection that are affected by exercise, which were found or their functions were expanded, which strengthened the connection between organs of the whole body, highlighting the importance of exercise and contributing to the diagnosis, prevention, and treatment of osteoporosis and sarcopenia in the clinic.

Reduced expression of semaphorin 3A in osteoclasts causes lymphatic expansion in a Gorham-Stout disease (GSD) mouse model.

Gorham-Stout disease (GSD) is a sporadic chronic disease characterized by progressive bone dissolution, absorption, and disappearance along with lymphatic vessel infiltration in bone-marrow cavities. Although the osteolytic mechanism of GSD has been widely studied, the cause of lymphatic hyperplasia in GSD is rarely investigated. In this study, by comparing the RNA expression profile of osteoclasts (OCs) with that of OC precursors (OCPs) by RNA sequencing, we identified a new factor, semaphorin 3A (Sema3A), which is an osteoprotective factor involved in the lymphatic expansion of GSD. Compared to OCPs, OCs enhanced the growth, migration, and tube formation of lymphatic endothelial cells (LECs), in which the expression of Sema3A is low compared to that in OCPs. In the presence of recombinant Sema3A, the growth, migration, and tube formation of LECs were inhibited, further confirming the inhibitory effect of Sema3A on LECs in vitro. Using an LEC-induced GSD mouse model, the effect of Sema3A was examined by injecting lentivirus-expressing Sema3A into the tibiae in vivo. We found that the overexpression of Sema3A in tibiae suppressed the expansion of LECs and alleviated bone loss, whereas the injection of lentivirus expressing Sema3A short hairpin RNA (shRNA) into the tibiae caused GSD-like phenotypes. Histological staining further demonstrated that OCs decreased and osteocalcin increased after Sema3A lentiviral treatment, compared with the control. Based on the above results, we propose that reduced Sema3A in OCs is one of the mechanisms contributing to the pathogeneses of GSD and that expressing Sema3A represents a new approach for the treatment of GSD.

The Efficacy and Safety of an Intra-articular Dual-Acting Antibacterial Agent (TNP-2092) for Implant Infection-Associated Methicillin-Resistant Staphylococcus aureus.

Owing to the presence of microbial biofilm on the implant, the eradication of biofilm-associated infections poses a challenge for antibiotic therapies. The study aimed to investigate the efficacy and safety of the novel antibiotic agent TNP-2092 in the context of implant infections. In vivo, rats with periprosthetic joint infection (PJI) treated with antibiotics showed an increase in body weight and decrease in swelling, temperature, and width of knee, compared with the control group. Meanwhile, inflammatory markers in synovium and serum were decreased in the TNP-2092 group, consistent with the pathological results. Moreover, TNP-2092 was effective in eliminating bacteria and disruption biofilm formation, and further alleviated the abnormal bone absorption and reactive bone changes around the prosthesis. In conclusion, intra-articular injection of TNP-2092 is safe and effective in treating knee PJI in a rat model. The study provides a foundation for the future utilization of TNP-2092 in the management of implant-related infections.

Identifying potential ferroptosis key genes for diagnosis and treatment of postmenopausal osteoporosis through competitive endogenous RNA network analysis

ObjectivePostmenopausal osteoporosis (PMOP) is a common systemic metabolic bone disorder that is owing to the reduced estrogen secretion and imbalance of bone absorption and bone formation in postmenopausal women. Ferroptosis has been identified as a novel modulatory mechanism of osteoporosis. Nevertheless, the particular modulatory mechanism between ferroptosis and PMOP is still unclear. The objective of the current investigation was to detect potential biomarkers connected to ferroptosis in PMOP and discover its probable mechanism through bioinformatics. MethodsWe downloaded PMOP-related microarray datasets from the database of Gene Expression Omnibus (GEO) and obtained the differentially expressed genes (DEGs). Utilizing bioinformatics analysis, the DEGs were intersected with the ferroptosis dataset to obtain ferroptosis-connected mRNAs. Enrichment analysis employing KOBAS 3.0 was conducted to comprehend the biological functions and enrichment pathways of the DEGs. The generation of the protein-protein interaction (PPI) network was conducted with the aim of identifying central genes. Lastly, the coexpression and competitive endogenous RNA (ceRNA) networks were built using Cytoscape. With the help of external datasets GSE56815 to verify the reliability of the hub genes by plotting ROC curves. ResultsWe identified 178 DE microRNAs (miRNAs), 138 DE circular RNAs (circRNAs), and 86 ferroptosis-related mRNAs. Enrichment analysis exhibited that mRNAs were primarily connected with the signaling pathways of PI3K/Akt, metabolism, mTOR, FoxO, HIF-1, AMPK, MAPK, ferroptosis, VEGF, and NOD-like receptors. Generation of the PPI network detected eight hub genes. The circRNA/miR-23b-3p/PTEN axis may relieve PMOP by inhibiting ferroptosis through targeting the pathway of PI3K/Akt signaling, which is a vital modulatory pathway for PMOP progression. Moreover, the ROC curves ultimately indicates that the four hub genes have greater diagnostic importance in PMOP samples in contrast to the normal group samples, which may be possible markers for PMOP diagnosis. ConclusionsBioinformatics analysis identified four hub genes, namely, PTEN, SIRT1, VEGFA, and KRAS, as potential biomarkers for PMOP diagnosis and management. Moreover, the circRNA/miR-23b-3p/PTEN axis may relieve PMOP by suppressing ferroptosis through targeting the pathway of PI3K/Akt signaling, providing a new avenue to explore the pathogenesis of PMOP.

Integrated microbiome and metabolomics revealed the protective effect of baicalin on alveolar bone inflammatory resorption in aging

BackgroundWith the growing aging population and longer life expectancy, periodontitis and tooth loss have become major health concerns. The gut microbiota, as a key regulator in bone homeostasis, has gathered immense interest. Baicalin, a flavonoid compound extracted from Scutellaria baicalensis Georgi, has shown antioxidant and anti-inflammatory activities. PurposeThis study investigated, for the first time, the protective mechanism of baicalin against alveolar bone inflammatory resorption in aging mice by regulating intestinal flora and metabolites, as well as intestinal barrier function. MethodsA ligature-induced periodontitis model was established in d-galactose (D-gal)-induced aging mice, and baicalin was administered at different dosages for 13 weeks. Body weight was measured weekly. The antioxidant and anti-inflammatory activity of baicalin were evaluated using serum superoxide dismutase (SOD), malonaldehyde (MDA), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels. The immune capability was assessed by thymus and spleen indices. Histopathological changes were observed in the heart, liver, ileum, and periodontal tissues. Alveolar bone absorption of maxillary second molars was examined, and osteoclasts were counted by tartrate-resistant acid phosphatase (TRAP) staining. Furthermore, fecal samples were analyzed using 16S rRNA sequencing and non-targeted metabolomics to identify differences in intestinal bacterial composition and metabolites. ResultsBaicalin exhibited anti-aging properties, as evidenced by increased SOD activity and decreased levels of MDA, IL-6, and TNF-α in serum compared to the control group. Baicalin also ameliorated alveolar bone loss in the d-gal-induced aging-periodontitis group (p < 0.05). Furthermore, baicalin restored ileal permeability by up-regulating the expression of ZO-1 and occludin in aging-periodontitis groups (p < 0.05). Alpha diversity analysis indicated that baicalin-treated mice harbored a higher diversity of gut microbe. PCoA and ANOSIM results revealed significant dissimilarity between groups. The Firmicutes/Bacteroidetes (F/B) ratio, which decreased in periodontitis mice, was restored by baicalin treatment. Additionally, medium-dosage baicalin promoted the production of beneficial flavonoids, and enriched short-chain fatty acids (SCFAs)-producing bacteria. ConclusionIntestinal homeostasis is a potential avenue for treating age-related alveolar bone loss. Baicalin exerts anti-inflammatory, antioxidant, and osteo-protective properties by regulating the gut microbiota and metabolites.

Integrating Virtual Surgical Planning and 3D-Printed Tools with Iliac Bone Grafts for Orbital and Zygomatic Reconstruction in Hemifacial Microsomia Patients.

Hemifacial Microsomia (HFM) is the second most common congenital craniofacial malformation syndrome, and the complexity of HFM makes its treatment challenging. The present study aimed to introduce a new approach of utilization of virtual surgical planning (VSP) and 3D-printed surgical adjuncts for maxillofacial reconstruction. Five HFM patients were included in this study. All participants were provided with a full VSP, including the design of osteotomy lines, the design and fabrication of 3D-printed cutting guides, fixation plates, and titanium mesh for implantation. With the assistance of 3D-printed cutting guides and fixation plates, the orbital deformities were corrected, and a 3D-printed titanium mesh combined with iliac cancellous bone graft was applied to reconstruct the zygomatic arch. The surgical accuracy, effectiveness, and bone absorption rate were evaluated. All patients completed the entirely digital treatment process without experiencing severe complications. The surgical adjuncts were effective in aligning the movement of the bone segments with the surgical plan, resulting in mean 3D deviations (1.0681 ± 0.15 mm) and maximum 3D deviations (3.1127 ± 0.44 mm). The image fusion results showed that the patients' postoperative position of the maxilla, zygoma, and orbital rim was consistent with the virtual surgical plan, with only a slight increase in the area of bone grafting. The postoperative measurements showed significant improvement in the asymmetry indices of Er (AI of Er: from 17.91 ± 3.732 to 5.427 ± 1.389 mm, p = 0.0001) and FZ (AI of FZ: from 7.581 ± 1.435 to 4.070 ± 1.028 mm, p = 0.0009) points. In addition, the observed bone resorption rate at the 6-month follow-up across the five patients was 45.24% ± 3.13%. In conclusion, the application of VSP and 3D-printed surgical adjuncts demonstrates significant value in enhancing the precision and effectiveness of surgical treatments for HFM. A 3D-printed titanium mesh combined with iliac cancellous bone graft can be considered an ideal alternative for the reconstruction of the zygomatic arch.

Progress in Prevention and Treatment of Acute Bone Loss in Orthopedics

Orthopedic patients need to perform limb immobilization for several days to several weeks due to fracture or other special circumstances. When the function of a certain part or the whole body is restricted, the activity of osteoclasts will be enhanced and its life activity will surpass that of osteoblasts, so local or even whole body bone loss will occur. Acute bone loss usually occurs within a few weeks after the immobilization of limbs. At this stage, the patient’s bone mass will decrease sharply, and the patient is prone to osteoporotic refracture. After that, the bone mass will gradually recover, but the speed of bone formation and bone absorption is difficult to reach a balanced state, and the bone mass of patients will continue to decline after it has recovered to a certain degree. After acute progressive bone loss, a large number of bones were lost and the strength of bones decreased. It is often difficult to recover to the level before fracture for a long time, which undoubtedly increases the risk of osteoporosis and related refractures. According to this common phenomenon of bone loss, clinical treatment varies greatly. After a series of research and practice, clinicians summed up some rules and put forward some feasible suggestions, thus strengthening clinicians’ understanding of the treatment of acute bone loss, effectively improving the treatment effect of acute bone loss, having far-reaching significance for preventing and treating osteoporosis, reducing the risk of fracture, and improving the long-term prognosis of patients.