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1.
JBMR Plus ; 8(5): ziae034, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38586475

RESUMO

Mutations in PLEKHM1 cause osteopetrosis in humans and rats. The germline and osteoclast conditional deletions of Plekhm1 gene in mice lead to defective osteoclast bone resorption and increased trabecular bone mass without overt abnormalities in other organs. As an adaptor protein, pleckstrin homology and RUN domain containing M1 (PLEKHM1) interacts with the key lysosome regulator small GTPase RAB7 via its C-terminal RUBICON homologous (RH) domain. In this study, we have conducted a structural-functional study of the PLEKHM1 RH domain and RAB7 interaction in osteoclasts in vitro. The single mutations of the key residues in the Plekhm1 RH predicted from the crystal structure of the RUBICON RH domain and RAB7 interface failed to disrupt the Plekhm1-Rab7 binding, lysosome trafficking, and bone resorption. The compound alanine mutations at Y949-R954 and L1011-I1018 regions decreased Plekhm1 protein stability and Rab7-binding, respectively, thereby attenuated lysosome trafficking and bone resorption in osteoclasts. In contrast, the compound alanine mutations at R1060-Q1068 region were dispensable for Rab7-binding and Plekhm1 function in osteoclasts. These results indicate that the regions spanning Y949-R954 and L1011-I1018 of Plekhm1 RH domain are functionally important for Plekhm1 in osteoclasts and offer the therapeutic targets for blocking bone resorption in treatment of osteoporosis and other metabolic bone diseases.

2.
World J Stem Cells ; 16(3): 267-286, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38577236

RESUMO

BACKGROUND: 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. AIM: To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement (OTM) model and explore the underlying mechanisms. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

3.
Front Immunol ; 15: 1335181, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38529278

RESUMO

Introduction: Temporomandibular joint (TMJ) osteoarthritis (OA) is a common TMJ degenerative disease with an unclear mechanism. Synovial fluid (SF), an important component of TMJ, contains various proteins and metabolites that may directly contribute to OA. The present study aimed to investigate the influence of SF in TMJOA at the metabolite level. Methods: Untargeted and widely targeted metabolic profiling were employed to identify metabolic changes in SF of 90 patients with different TMJOA grades according to TMJ magnetic resonance imaging. Results: A total 1498 metabolites were detected. Most of the metabolites were amino acids and associated metabolites, benzene and substituted derivatives, and lipids. Among patients with mild, moderate and severe TMJOA, 164 gradually increasing and 176 gradually decreasing metabolites were identified, indicating that biosynthesis of cofactors, choline metabolism, mineral absorption and selenocompound metabolism are closely related to TMJOA grade. Combined metabolomics and clinical examination revealed 37 upregulated metabolites and 16 downregulated metabolites in patients with pain, of which 19 and 26 metabolites were positively and negatively correlated, respectively, with maximum interincisal opening. A model was constructed to diagnose TMJOA grade and nine biomarkers were identified. The identified metabolites are key to exploring the mechanism of TMJOA. Discussion: In the present study, a metabolic profile was constructed and assessed using a much larger number of human SF samples from patients with TMJOA, and a model was established to contribute to the diagnosis of TMJOA grade. The findings expand our knowledge of metabolites in human SF of TMJOA patients, and provide an important basis for further research on the pathogenesis and treatment of TMJOA.


Assuntos
Osteoartrite , Transtornos da Articulação Temporomandibular , Humanos , Líquido Sinovial/metabolismo , Articulação Temporomandibular/patologia , Osteoartrite/metabolismo , Transtornos da Articulação Temporomandibular/metabolismo , Transtornos da Articulação Temporomandibular/patologia , Metabolômica/métodos
4.
Cureus ; 16(1): e53250, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38435924

RESUMO

Pseudohypoparathyroidism is a rare disorder characterized by end-organ resistance to intact parathyroid hormone (PTH) and concomitant laboratory findings of hypocalcemia and hyperphosphatemia. Radiologic evidence of the disease may manifest as a variety of bone abnormalities. This case describes an 11-year-old female with a history of repaired bilateral slipped capital femoral epiphysis who presented with a limited range of motion of the bilateral upper extremities. Laboratory findings were consistent with pseudohypoparathyroidism. Radiographs revealed subchondral resorption of bilateral clavicular heads and multiple ribs and band lucencies of proximal humeral metaphyses, along with vara deformity and inferior subluxation of the humeral heads. This presentation adds to the spectrum of potential radiographic manifestations of pseudohypoparathyroidism.

5.
Odontology ; 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457086

RESUMO

The aim of this study was to investigate the influence of systemic antibiotic therapy on the development and progression of induced apical periodontitis (AP) in Wistar rats. Fifty-six rats were submitted to pulp exposure of the lower left first molar for the induction of AP. On the same day, intraperitoneal antibiotic therapy was administered once a day, for 15 days, until euthanasia. The groups were formed according to the different treatments (n = 8): C-control; GEN-treated with gentamicin (10 mg/Kg); AC-treated with amoxicillin (100 mg/Kg); MZ-treated with metronidazole (40 mg/Kg); AMP-treated with ampicillin (100 mg/Kg); AMC group-treated with amoxicillin + clavulanic acid (100 mg/kg); CLI-treated with clindamycin (60 mg/kg). After euthanasia, the jaws were collected and processed for (1) histological and histometric analysis using hematoxylin and eosin staining, (2) analysis of collagen fibers using Picrosirius Red staining and (3) bacteriological analysis using Brown-Brenn staining. The data were analyzed statistically (p < 0.05). AP induction was confirmed in all groups. The AMC group had the lower intensity of inflammatory infiltrate (p = 0.028) and less periapical bone resorption compared to control (p = 0.006). Regarding collagen maturation, PSR staining revealed a predominance of mature collagen fibers in all groups. The AC and AMC groups had the lower amount of mature fibers and the highest amount of immature fibers, compared to all other groups (p < 0.001). All groups showed bacterial contamination; however, the AC and AMC groups showed a lower extent of bacterial contamination compared to the control (p < 0.001). It can be concluded that systemic antibiotic therapy influences the development and progression of induced AP.

6.
BMC Musculoskelet Disord ; 25(1): 201, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38454383

RESUMO

OBJECTIVE: To introduce the method and experience of treating critical-sized tibial bone defect by taking large iliac crest bone graft. METHODS: From January 2020 to January 2022, iliac crest bone grafting was performed in 20 patients (10 men and 10 women) with critical-sized tibial bone defect. The mean length of bone defect was 13.59 ± 3.41. Bilateral iliac crest grafts were harvested, including the inner and outer plates of the iliac crest and iliac spine. The cortical bone screw was used to integrate two iliac bone blocks into one complex. Locking plate was used to fix the graft-host complex, supplemented with reconstruction plate to increase stability when necessary. Bone healing was evaluated by cortical bone fusion on radiographs at follow-up, iliac pain was assessed by VAS score, and lower limb function was assessed by ODI score. Complications were also taken into consideration. RESULTS: The average follow-up time was 27.4 ± 5.6 (Range 24-33 months), the mean VAS score was 8.8 ± 1.9, the mean ODI score was 11.1 ± 1.8, and the number of cortical bone fusion in the bone graft area was 3.5 ± 0.5. Satisfactory fusion was obtained in all cases of iliac bone transplant-host site. No nonunion, shift or fracture was found in all cases. No infection and bone resorption were observed that need secondary surgery. One patient had dorsiflexion weakness of the great toe. Hypoesthesia of the dorsal foot was observed in 2 patients. Ankle stiffness and edema occurred in 3 patients. Complications were significantly improved by physical therapy and rehabilitation training. CONCLUSION: For the cases of critical-sized tibial bone defect, the treatment methods are various. In this paper, we have obtained satisfactory results by using large iliac bone graft to treat bone defect. This approach can not only restore the integrity of the tibia, but also obtain good stability with internal fixation, and operation skills are more acceptable for surgeons. Therefore, it provides an alternative surgical method for clinicians.


Assuntos
Fraturas Ósseas , Procedimentos de Cirurgia Plástica , Masculino , Humanos , Feminino , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Ílio/transplante , Fixação Interna de Fraturas , Transplante Ósseo/métodos , Resultado do Tratamento
7.
Oral Dis ; 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38462960

RESUMO

OBJECTIVES: To explore the effects of cathepsin K (CTSK) inhibition on type H vessel formation and alveolar bone resorption within periodontitis. METHODS: Conditioned media derived from preosteoclasts pretreated with the CTSK inhibitor odanacatib (ODN), ODN supplemented small interfering RNA targeting PDGF-BB (si-PDGF-BB), or PBS were prepared, to assess their proangiogenic effects on endothelial cells (HUVECs). A series of angiogenic-related assays were conducted to evaluate HUVEC proliferation, migration, and tube formation abilities in vitro. In addition, qRT-PCR and Western blot assays were employed to examine the expression levels of genes/proteins related to PDGF-BB/PDGFR-ß axis components. A mouse periodontitis model was established to evaluate the effects of CTSK inhibition on type H vessel formation. RESULTS: CTSK inhibition promoted PDGF-BB secretion from preosteoclasts and proliferation, migration, and tube formation activities of HUVECs in vitro. However, the conditioned medium from preosteoclasts pretreated by si-PDGF-BB impaired the angiogenic activities of HUVECs. This promoted angiogenesis function by CTSK inhibition may be mediated by the PDGF-BB/PDGFR-ß axis. Functionally, in vivo studies demonstrated that CTSK inhibition significantly accelerated type H vessel formation and alleviated bone loss within periodontitis. CONCLUSION: CTSK inhibition promotes type H vessel formation and attenuates alveolar bone resorption within periodontitis via PDGF-BB/PDGFR-ß axis.

8.
JBMR Plus ; 8(1): ziad009, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38549711

RESUMO

PLS3 loss-of-function mutations in humans and mice cause X-linked primary osteoporosis. However, it remains largely unknown how PLS3 mutations cause osteoporosis and which function PLS3 plays in bone homeostasis. A recent study showed that ubiquitous Pls3 KO in mice results in osteoporosis. Mainly osteoclasts were impacted in their function However, it has not been proven if osteoclasts are the major cell type affected and responsible for osteoporosis development in ubiquitous Pls3 KO mice. Here, we generated osteoclast-specific Pls3 KO mice. Additionally, we developed a novel polyclonal PLS3 antibody that showed specific PLS3 loss in immunofluorescence staining of osteoclasts in contrast to previously available antibodies against PLS3, which failed to show PLS3 specificity in mouse cells. Moreover, we demonstrate that osteoclast-specific Pls3 KO causes dramatic increase in resorptive activity of osteoclasts in vitro. Despite these findings, osteoclast-specific Pls3 KO in vivo failed to cause any osteoporotic phenotype in mice as proven by micro-CT and three-point bending test. This demonstrates that the pathomechanism of PLS3-associated osteoporosis is highly complex and cannot be reproduced in a system singularly focused on one cell type. Thus, the loss of PLS3 in alternative bone cell types might contributes to the osteoporosis phenotype in ubiquitous Pls3 KO mice.

9.
Front Immunol ; 15: 1254516, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38455060

RESUMO

There exists a bidirectional relationship between oral health and general well-being, with an imbalance in oral symbiotic flora posing a threat to overall human health. Disruptions in the commensal flora can lead to oral diseases, while systemic illnesses can also impact the oral cavity, resulting in the development of oral diseases and disorders. Porphyromonas gingivalis and Fusobacterium nucleatum, known as pathogenic bacteria associated with periodontitis, play a crucial role in linking periodontitis to accompanying systemic diseases. In periodontal tissues, these bacteria, along with their virulence factors, can excessively activate the host immune system through local diffusion, lymphatic circulation, and blood transmission. This immune response disruption contributes to an imbalance in osteoimmune mechanisms, alveolar bone resorption, and potential systemic inflammation. To restore local homeostasis, a deeper understanding of microbiota-host interactions and the immune network phenotype in local tissues is imperative. Defining the immune network phenotype in periodontal tissues offers a promising avenue for investigating the complex characteristics of oral plaque biofilms and exploring the potential relationship between periodontitis and associated systemic diseases. This review aims to provide an overview of the mechanisms underlying Porphyromonas gingivalis- and Fusobacterium nucleatum-induced alveolar bone resorption, as well as the immunophenotypes observed in host periodontal tissues during pathological conditions.


Assuntos
Perda do Osso Alveolar , Periodontite , Humanos , Porphyromonas gingivalis , Inflamação , Fusobacterium nucleatum/fisiologia
10.
Biochem Biophys Res Commun ; 705: 149743, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38442445

RESUMO

Neutrophil extracellular traps (NETs) released by neutrophils upon inflammation or infection, act as an innate immune defense against pathogens. NETs also influence inflammatory responses and cell differentiation in host cells. Osteoclasts, which are derived from myeloid stem cells, are critical for the bone remodeling by destroying bone. In the present study, we explores the impact of NETs, induced by the inflammatory agent calcium ionophore A23187, on the differentiation and activation of osteoclasts, potentially through suppressing RANK expression. Our results collectively suggested that the inhibition of RANKL-mediated osteoclastogenesis by NETs might lead to the suppression of excessive bone resorption during inflammation.


Assuntos
Reabsorção Óssea , Armadilhas Extracelulares , Humanos , Osteogênese , Osteoclastos , Neutrófilos , Diferenciação Celular , Inflamação , Ligante RANK
11.
Sci Rep ; 14(1): 7358, 2024 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548807

RESUMO

Cathepsin K (CatK), an essential collagenase in osteoclasts (OCs), is a potential therapeutic target for the treatment of osteoporosis. Using live-cell imaging, we monitored the bone resorptive behaviour of OCs during dose-dependent inhibition of CatK by an ectosteric (Tanshinone IIA sulfonate) and an active site inhibitor (odanacatib). CatK inhibition caused drastic reductions in the overall resorption speed of OCs. At IC50 CatK-inhibitor concentration, OCs reduced about 40% of their trench-forming capacity and at fourfold IC50 concentrations, a > 95% reduction was observed. The majority of CatK-inhibited OCs (~ 75%) were involved in resorption-migration-resorption episodes forming adjacent pits, while ~ 25% were stagnating OCs which remained associated with the same excavation. We also observed fusions of OCs during the resorption process both in control and inhibitor-treated conditions, which increased their resorption speeds by 30-50%. Inhibitor IC50-concentrations increased OC-fusion by twofold. Nevertheless, more fusion could not counterweigh the overall loss of resorption activity by inhibitors. Using an activity-based probe, we demonstrated the presence of active CatK at the resorbing front in pits and trenches. In conclusion, our data document how OCs respond to CatK-inhibition with respect to movement, bone resorption activity, and their attempt to compensate for inhibition by activating fusion.


Assuntos
Conservadores da Densidade Óssea , Reabsorção Óssea , Osteoporose , Humanos , Osteoclastos , Conservadores da Densidade Óssea/farmacologia , Reabsorção Óssea/tratamento farmacológico , Osteoporose/tratamento farmacológico , Catepsina K
12.
J Funct Biomater ; 15(3)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38535258

RESUMO

Excessive osteoclast activity can promote periodontitis-associated bone destruction. The inhibitory mechanisms of Weissella cibaria strains CMU and CMS1 against periodontitis have not yet been fully elucidated. In this study, we aimed to investigate whether heat-killed (HK) W. cibaria CMU and CMS1 or their respective cell-free supernatants (CFSs) inhibit osteoclast differentiation and bone resorption in response to receptor activator of nuclear factor kappa-B ligand (RANKL)-treated RAW 264.7 cells. TRAP (tartrate-resistant acid phosphatase) staining and bone resorption assays revealed that both HK bacteria and CFSs significantly suppressed the number of TRAP-positive cells, TRAP activity, and bone pit formation compared to the RANKL-treated control (p < 0.05). HK bacteria dose-dependently inhibited osteoclastogenesis while selectively regulating certain genes in CFSs (p < 0.05). We found that disrupting the direct interaction between HK bacteria and RAW 264.7 cells abolished the inhibitory effect of HK bacteria on the expression of osteoclastogenesis-associated proteins (c-Fos, nuclear factor of activated T cells c1 (NFATc1), and cathepsin K). These results suggest that dead bacteria suppress osteoclast differentiation more effectively than the metabolites and may serve as beneficial agents in preventing periodontitis by inhibiting osteoclast differentiation via direct interaction with cells.

13.
J Inflamm Res ; 17: 1607-1619, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495340

RESUMO

Metrnl, recently identified as an adipokine, is a secreted protein notably expressed in white adipose tissue, barrier tissues, and activated macrophages. This adipokine plays a pivotal role in counteracting obesity-induced insulin resistance. It enhances adipose tissue functionality by promoting adipocyte differentiation, activating metabolic pathways, and exerting anti-inflammatory effects. Extensive research has identified Metrnl as a key player in modulating inflammatory responses and as an integral regulator of muscle regeneration. These findings position Metrnl as a promising biomarker and potential therapeutic target in treating inflammation-associated pathologies. Despite this, the specific anti-inflammatory mechanisms of Metrnl in immune-mediated osteolysis and arthritis remain elusive, warranting further investigation. In this review, we will briefly elaborate on the role of Metrnl in anti-inflammation function in inflammation-related osteolysis, arthritis, and pathological bone resorption, which could facilitate Metrnl's clinical application as a novel therapeutic strategy to prevent bone loss. While the pathogenesis of elbow stiffness remains elusive, current literature suggests that Metrnl likely exerts a pivotal role in its development.

14.
BMC Oral Health ; 24(1): 325, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468273

RESUMO

OBJECTIVE: Marginal alveolar bone loss is one of the key features of periodontitis and can be observed via panoramic radiographs. This study aimed to establish a cascading learning method with deep learning (DL) for precise radiographic bone loss (RBL) measurements at specific tooth positions. MATERIALS AND METHODS: Through the design of two tasks for tooth position recognition and tooth semantic segmentation using the SegFormer model, specific tooth's crown, intrabony portion, and suprabony portion of the roots were obtained. The RBL was subsequently measured by length through these three areas using the principal component analysis (PCA) principal axis. RESULTS: The average intersection over union (IoU) for the tooth position recognition task was 0.8906, with an F1-score of 0.9338. The average IoU for the tooth semantic segmentation task was 0.8465, with an F1-score of 0.9138. When the two tasks were combined, the average IoU was 0.7889, with an F1-score of 0.8674. The correlation coefficient between the RBL prediction results based on the PCA principal axis and the clinicians' measurements exceeded 0.85. Compared to those of the other two methods, the average precision of the predicted RBL was 0.7722, the average sensitivity was 0.7416, and the average F1-score was 0.7444. CONCLUSIONS: The method for predicting RBL using DL and PCA produced promising results, offering rapid and reliable auxiliary information for future periodontal disease diagnosis. CLINICAL RELEVANCE: Precise RBL measurements are important for periodontal diagnosis. The proposed RBL-SF can measure RBL at specific tooth positions and assign the bone loss stage. The ability of the RBL-SF to measure RBL at specific tooth positions can guide clinicians to a certain extent in the accurate diagnosis of periodontitis.


Assuntos
Perda do Osso Alveolar , Periodontite , Dente , Humanos , Perda do Osso Alveolar/diagnóstico por imagem , Processo Alveolar , Periodontite/diagnóstico por imagem , Coroa do Dente
15.
Int J Mol Sci ; 25(5)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38473802

RESUMO

Glucose-insulinotropic polypeptide (GIP) is an incretin hormone that induces insulin secretion and decreases blood glucose levels. In addition, it has been reported to suppress osteoclast formation. Native GIP is rapidly degraded by dipeptidyl peptidase-4 (DPP-4). (D-Ala2)GIP is a newly developed GIP analog that demonstrates enhanced resistance to DPP-4. This study aimed to evaluate the influence of (D-Ala2)GIP on osteoclast formation and bone resorption during lipopolysaccharide (LPS)-induced inflammation in vivo and in vitro. In vivo, mice received supracalvarial injections of LPS with or without (D-Ala2)GIP for 5 days. Osteoclast formation and bone resorption were evaluated, and TNF-α and RANKL expression were measured. In vitro, the influence of (D-Ala2)GIP on RANKL- and TNF-α-induced osteoclastogenesis, LPS-triggered TNF-α expression in macrophages, and RANKL expression in osteoblasts were examined. Compared to the LPS-only group, calvariae co-administered LPS and (D-Ala2)GIP led to less osteoclast formation, lower bone resorption, and decreased TNF-α and RANKL expression. (D-Ala2)GIP inhibited osteoclastogenesis induced by RANKL and TNF-α and downregulated TNF-α expression in macrophages and RANKL expression in osteoblasts in vitro. Furthermore, (D-Ala2)GIP suppressed the MAPK signaling pathway. The results suggest that (D-Ala2)GIP dampened LPS-triggered osteoclast formation and bone resorption in vivo by reducing TNF-α and RANKL expression and directly inhibiting osteoclastogenesis.


Assuntos
Reabsorção Óssea , Osteoclastos , Animais , Camundongos , Osteoclastos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Lipopolissacarídeos/farmacologia , Glucose/metabolismo , Reabsorção Óssea/metabolismo , Peptídeos/metabolismo
16.
Cell Transplant ; 33: 9636897241236584, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38501500

RESUMO

Aging, space flight, and prolonged bed rest have all been linked to bone loss, and no effective treatments are clinically available at present. Here, with the rodent hindlimb unloading (HU) model, we report that the bone marrow (BM) microenvironment was significantly altered, with an increased number of myeloid cells and elevated inflammatory cytokines. In such inflammatory BM, the osteoclast-mediated bone resorption was greatly enhanced, leading to a shifted bone remodeling balance that ultimately ends up with disuse-induced osteoporosis. Using Piezo1 conditional knockout (KO) mice (Piezo1fl/fl;LepRCre), we proved that lack of mechanical stimuli on LepR+ mesenchymal stem cells (MSCs) is the main reason for the pathological BM inflammation. Mechanically, the secretome of MSCs was regulated by mechanical stimuli. Inadequate mechanical load leads to increased production of inflammatory cytokines, such as interleukin (IL)-1α, IL-6, macrophage colony-stimulating factor 1 (M-CSF-1), and so on, which promotes monocyte proliferation and osteoclastic differentiation. Interestingly, transplantation of 10% cyclic mechanical stretch (CMS)-treated MSCs into HU animals significantly alleviated the BM microenvironment and rebalanced bone remodeling. In summary, our research revealed a new mechanism underlying mechanical unloading-induced bone loss and suggested a novel stem cell-based therapy to potentially prevent disuse-induced osteoporosis.


Assuntos
Reabsorção Óssea , Osteoporose , Camundongos , Animais , Secretoma , Reabsorção Óssea/patologia , Camundongos Knockout , Inflamação , Citocinas , Canais Iônicos
17.
J Clin Med ; 13(6)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38542018

RESUMO

Background/Objectives: This research investigates the nuanced factors influencing peri-implant bone resorption in implant-supported fixed prostheses, with a focus on age, gender, implant location, time since prosthetic loading, and material characteristics. Methods: Records from a dental clinic in Oradea, Romania, between 1 January 2017 and 1 January 2023, were scrutinized and were selected by means of purposive sampling. All records were analyzed between 1 May 2023 and 15 June 2023. A total of 160 implants were included, and the prosthetic restorations were either metal-ceramic or zirconia. Implants from a single manufacturer were used, and a standardized loading protocol was followed. The study examined variables such as age, gender, implant location, prosthetic material, and time since prosthetic loading. Results: A total of 160 implants were included, with 78 applied to female patients (48.8%) and 82 to male patients (51.2%). The age range of the patients undergoing dental implant procedures was 30 to 79 years. Implants were distributed between the mandible (51.2%) and maxilla (48.8%), with 49.4% placed in the posterior dental arches and 50.6% in the anterior dental arches. The majority of patients received metal-ceramic prosthetic reconstructions (76.9%). Statistical analysis revealed significant differences in resorption patterns between zirconia and metal-ceramic restorations (p < 0.001), with zirconia restorations exhibiting higher resorption in the mesial-vertical and distal-vertical planes compared to metal-ceramic restorations. Age-related factors showed a significant association with distal-vertical resorption (p = 0.017), with patients aged 60-69 years exhibiting higher resorption values compared to those aged 40-49 years. Gender differences were observed in mesial-horizontal resorption (p = 0.036), with male patients displaying higher resorption values compared to female patients. Implant location and time elapsed since implant loading did not show significant associations with resorption patterns. Conclusions: The study provides insights into the multifactorial nature of peri-implant resorption. Age, gender, and material characteristics contribute to variations, informing personalized treatment approaches. The findings facilitate a comprehensive understanding for clinicians, enhancing treatment planning and post-operative care.

18.
Biomed Pharmacother ; 172: 116258, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38350370

RESUMO

Optineurin (OPTN) is a widely expressed multifunctional articulatory protein that participates in cellular or mitochondrial autophagy, vesicular transport, and endoplasmic reticulum (ER) stress via interactions with various proteins. Skeletal development is a complex biological process that requires the participation of various osteoblasts, such as bone marrow mesenchymal stem cells (BMSCs), and osteogenic, osteoclastic, and chondrogenic cells. OPTN was recently found to be involved in the regulation of osteoblast activity, which affects bone metabolism. OPTN inhibits osteoclastogenesis via signaling pathways, including NF-κB, IFN-ß, and NRF2. OPTN can promote the differentiation of BMSCs toward osteogenesis and inhibit lipogenic differentiation by delaying BMSC senescence and autophagy. These effects are closely related to the development of bone metabolism disorders, such as Paget's disease of bone, rheumatoid arthritis, and osteoporosis. Therefore, this review aims to explore the role and mechanism of OPTN in the regulation of bone metabolism and related bone metabolic diseases. Our findings will provide new targets and strategies for the prevention and treatment of bone metabolic diseases.


Assuntos
Osso e Ossos , Proteínas de Ciclo Celular , Proteínas de Membrana Transportadoras , Humanos , Adenocarcinoma , Artrite Reumatoide , Autofagia , Transporte Biológico , Doenças Ósseas Metabólicas , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Ciclo Celular/metabolismo , Osso e Ossos/metabolismo , Animais
19.
Int Immunopharmacol ; 129: 111655, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38340423

RESUMO

Wear particles generated from the surface of implanted prostheses can lead to peri-implant osteolysis and subsequent aseptic loosening. In the inflammatory environment, extensive formation and activation of osteoclasts are considered the underlying cause of peri-implant osteolysis. Current medications targeting osteoclasts for the treatment of particle-induced bone resorption are not ideal due to significant side effects. Therefore, there is an urgent need to develop more effective drugs with fewer side effects. Norcantharidin (NCTD), a derivative of cantharidin extracted from blister beetles, is currently primarily used for the treatment of solid tumors in clinical settings. However, the potential role of NCTD in treating aseptic loosening of the prosthesis has not been reported. In this study, the in vitro results demonstrated that NCTD could effectively inhibit the formation of osteoclasts and bone resorption induced by the RANKL. Consistently, NCTD strongly inhibited RANKL-induced mRNA and protein levels of c-Fos and NFATc1, concomitant with reduced expression of osteoclast specific genes including TRAP, CTR and CTSK. The in vivo data showed that NCTD exerted significant protective actions against titanium particle-induced inflammation and subsequent osteolysis. The molecular mechanism investigation revealed that NCTD could suppress the activations of RANKL-induced MAPK (p38, ERK). Overall, these findings support the potential use of NCTD for the treatment of aseptic loosening following total joint arthroplasty.


Assuntos
Reabsorção Óssea , Compostos Bicíclicos Heterocíclicos com Pontes , Osteólise , Animais , Camundongos , Osteoclastos , Osteólise/induzido quimicamente , Osteólise/tratamento farmacológico , Osteólise/metabolismo , Titânio/efeitos adversos , NF-kappa B/metabolismo , Reabsorção Óssea/induzido quimicamente , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/patologia , Ligante RANK/metabolismo , Osteogênese , Camundongos Endogâmicos C57BL
20.
Artigo em Inglês | MEDLINE | ID: mdl-38380779

RESUMO

OBJECTIVES: The current guidelines recommend that immediate implants be placed in patients with thick (>1 mm) buccal bone due to the inevitable tissue remodeling that follows tooth extraction. The aim of the current study was to investigate the effect of buccal bone thickness on bone resorption in immediate implant placement and compare two measuring techniques of the aforementioned resorption. MATERIALS: The present study was designed as a prospective nonrandomized, controlled clinical trial. A total of 30 implants were split between the two study arms, thin buccal bone and thick buccal bone. The primary outcome was to assess vertical bone changes radiographically by cone beam scans preoperatively, at 2 months and 18 months after implant placement in patients with thin and thick buccal plate. Secondary outcomes included the change in the thickness of the buccal bony plate, marginal bone loss, and pink esthetic score. RESULTS: Only 26 implants were statistically analyzed as one early failure was observed in each group. Furthermore, 2 patients of the thick group withdrew from the study. Cone beam computed tomography measurements revealed that at 2 months the vertical bone loss was 1.09 for the thin group and 0.85 for the thick group. The buccal bone plate resorption of the thin group was 0.39 mm while it was 0.52 mm for the thick group. The buccal bone plate was 1.25 mm in the thin group and 1.88 mm in the thick group. The PES did not show any significant difference with very good esthetic results. CONCLUSION: Within the limitations of the current study, the amount of buccal bone plate resorption and the subsequent thickness obtained after implantation in both groups suggest successful long-term results. The two measuring techniques have proven to be comparable and reliable in the measurement of buccal bony plate changes. https://classic. CLINICALTRIALS: gov/ct2/results?cond=&term=NCT04731545&cntry=EG&state=&city=&dist=.

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