UNASSIGNED: Osteoimmunology recognizes the relationship between bone cells and immune cells. Chronic osteoimmune dysregulation is present in bone marrow defects of the jaw (BMDJ) as fatty-degenerative osteonecrosis (FDOJ). In comparison to samples from healthy jaw bone, the cytokine analysis of samples of BMDJ/FDOJ from 128 patients showed downregulated TNF-α and IL-6 expression and the singular overexpression of the chemokine RANTES/CCL5.
UNASSIGNED: This paper raises the question of whether the osteoimmune defects due to incomplete wound healing in BMDJ/FDOJ in 128 patients are related to dysregulation of the Th1/Th2 ratio and regulatory T cell (T-reg) expression in a control group of 197 BMDJ/FDOJ patients, each presenting with BMDJ/FJOD and one of seven different immune disorders.
UNASSIGNED: In the control group, serum concentrations of the cytokines IFN-y and IL-4 were determined after stimulated cytokine release and displayed as Th1/Th2 ratios.
UNASSIGNED: Data show a shift in Th2 in more than 80% (n = 167) of the control cohort of 197 chronically ill patients with concomitant BMDJ/FDOJ. In these 167 subjects, the Th1/Th2 ratio was <6.1 demonstrating impaired immune regulation. Forty-seven subjects or 30% showed not only a shift in Th2 but also excessive T-reg overactivation with levels of >1.900 pg/mL, indicating strongly downregulated immune activity.
UNASSIGNED: BMDJ/FDOJ is characterized by a lack of Th1 cytokines and an excessive expression of RANTES/CCL5 and IL-1ra and, thus, the inversion of an acute inflammatory cytokine pattern. In contrast, abdominal fat contains a very high proportion of regulatory Th1 cells and produces an inflammatory immune response through the high overexpression of TNF-α and IL-6. The lack of Th1 activation in BMDJ/FDOJ areas inhibits normal wound healing and supports the persistence of BMDJ/FDOJ.
UNASSIGNED: The Th1/Th2 ratio requires greater consideration, especially with respect to wound healing following dental surgical interventions, such as jaw surgery, implantation and augmentation, to avoid the emergence of the osteoimmune situation that is characteristic of BMDJ/FDOJ.

Jawbones and long bones, despite their shared skeletal lineage, frequently exhibit distinct origins and developmental pathways. Identifying specific progenitor subsets for mandibular osteogenesis remains challenging. Type II collagen is conventionally associated with cartilaginous structures, yet our investigation has identified the presence of type II collagen positive (Col2+) cells within the jawbone development and regeneration. The role of Col2+ cells in jawbone morphogenesis and repair has remained enigmatic. In this study, we analyze single-cell RNA sequencing data from mice jawbone at embryonic day 10.5. Through fate-mapping experiments, we have elucidated that Col2+ cells and their progeny are instrumental in mandibular osteogenesis across both fetal and postnatal stages. Furthermore, lineage tracing with a tamoxifen-inducible CreER system has established the pivotal role of Col2+ cells, marked by Col2-CreER and originating from the primordial Meckel\'s cartilage, in jawbone formation. Moreover, our research explored models simulating jawbone defects and tooth extraction, which underscored the osteogenic differentiation capabilities of postnatal Col2+ cells during repair. This finding not only highlights the regenerative potential of Col2+ cells but also suggests their versatility in contributing to skeletal healing and regeneration. In conclusion, our findings position Col2+ cells as essential in orchestrating osteogenesis throughout the continuum of mandibular development and repair.

BACKGROUND: Dental cone beam computed tomography (CBCT) is commonly used to evaluate cancellous bone density before dental implant surgery. However, to our knowledge, no measurement approach has been standardized yet. This study aimed to evaluate the relationship between three different regions of interest (ROI) methods on cancellous bone density at the dental implant site using dental CBCT images.
METHODS: Patients\' dental CBCT images (n = 300) obtained before dental implant surgery were processed using Mimics (Materialise, Leuven, Belgium). At the potential implant sites, the rectangle, cylinder, and surrounding cylinder ROI methods were used to measure bone density. Repeated measures one-way analysis of variance was performed to compare the three ROI methods in terms of measurement results. Pearson correlation analysis was performed to identify the likely pair-wise correlations between the three ROI methods.
RESULTS: The density value obtained using the surrounding cylinder approach (grayscale value [GV],523.56 ± 228.03) was significantly higher than the values obtained using the rectangle (GV, 497.04 ± 236.69) and cylinder (GV,493 ± 231.19) ROI methods in terms of results. Furthermore, significant correlations were noted between the ROI methods (r > 0.965; p < 0.001).
CONCLUSIONS: The density measured using the surrounding cylinder method was the highest. The choice of method may not influence the trends of measurement results.
BACKGROUND: This study was approved by the Institutional Review Board of China Medical University Hospital, No. CMUH111-REC3-205. Informed consent was waived by the Institutional Review Board of China Medical University Hospital, CMUH111-REC3-205, owing to the retrospective nature of the study.

Piezo1 and Piezo2 are recently reported mechanosensory ion channels that transduce mechanical stimuli from the environment into intracellular biochemical signals in various tissues and organ systems. Here, we show that Piezo1 and Piezo2 display a robust expression during jawbone development. Deletion of Piezo1 in neural crest cells causes jawbone malformations in a small but significant number of mice. We further demonstrate that disruption of Piezo1 and Piezo2 in neural crest cells causes more striking defects in jawbone development than any single knockout, suggesting essential but partially redundant roles of Piezo1 and Piezo2. In addition, we observe defects in other neural crest derivatives such as malformation of the vascular smooth muscle in double knockout mice. Moreover, TUNEL examinations reveal excessive cell death in osteogenic cells of the maxillary and mandibular arches of the double knockout mice, suggesting that Piezo1 and Piezo2 together regulate cell survival during jawbone development. We further demonstrate that Yoda1, a Piezo1 agonist, promotes mineralization in the mandibular arches. Altogether, these data firmly establish that Piezo channels play important roles in regulating jawbone formation and maintenance.

Extracellular vesicles (EVs) are the essential mediators of communication between different cells or tissues. EVs participate in the development, homeostasis, repair, and regeneration of tissues. Mesenchymal stem cells(MSCs) secrete a range of bioactive factors, which are important in MSC-mediated tissue regeneration. Great progress has been made in the research of EVs derived from MSCs (MSC-EVs) in the regeneration of dental and maxillofacial tissues. Emerging evidence confirmed that MSC-EVs can efficiently modulate the proliferation, differentiation, survival, and migration of stem or progenitor cells and stimulate the regeneration of the neurovascular system. MSC-EVs have been used in regenerating dental pulp, periodontium, jawbone, temporomandibular joint, and maxillofacial soft tissues. Having the advantages of low immunogenicity, versatile function, and suitability for large-scale production, EVs have excellent clinical application prospect. Along with investigations on molecular mechanisms of action and development of standard manufactory and testing systems, therapies u-sing MSC-EVs are promising strategies for regenerating dental and maxillofacial tissues.
胞外囊泡（EVs）是不同细胞间及多种组织间信号交流的重要途径，广泛参与组织发育、稳态维持和再生修复等过程。间充质干细胞（MSCs）分泌的EVs含有丰富的生物活性物质，是MSCs发挥促组织再生作用的重要分泌性成分之一。近年来，MSCs分泌的EVs（MSC-EVs）在牙及颌面组织修复再生中的研究取得快速进展。MSC-EVs已被证实可以有效促进牙及颌骨中干细胞和前体细胞的增殖、分化、存活、迁移，并加快血管神经再生，从而可应用于牙髓、牙周、颌骨、颞下颌关节及颌面软组织的再生。因为EVs具备免疫原性低、作用途径广、可规模化制备等优势，其临床应用潜力巨大。随着对EVs作用机理的深入探索和标准化制备及检测体系的建立，MSC-EVs治疗有望成为牙及颌面部组织再生的重要策略。.

The jawbone, a unique structure in the human body, undergoes faster remodeling than other bones due to the presence of stem cells and its distinct immune microenvironment. Long-term exposure of jawbones to an oral environment rich in microbes results in a complex immune balance, as shown by the higher proportion of activated macrophage in the jaw. Stem cells derived from the jawbone have a higher propensity to differentiate into osteoblasts than those derived from other bones. The unique immune microenvironment of the jaw also promotes osteogenic differentiation of jaw stem cells. Here, we summarize the various types of stem cells and immune cells involved in jawbone reconstruction. We describe the mechanism relationship between immune cells and stem cells, including through the production of inflammatory bodies, secretion of cytokines, activation of signaling pathways, etc. In addition, we also comb out cellular interaction of immune cells and stem cells within the jaw under jaw development, homeostasis maintenance and pathological conditions. This review aims to eclucidate the uniqueness of jawbone in the context of stem cell within immune microenvironment, hopefully advancing clinical regeneration of the jawbone.

BACKGROUND: The long time required for bone uptake of radiopharmaceutical material after injection for bone scintigraphy is a burden for patients with poor health. Thus, to assess whether the uptake time could be reduced for single-photon emission computed tomography (SPECT) of the jawbone, this study evaluated differences in maximum standardized uptake values (SUVmax) within patients using SPECT imaging at 2 and 3 hours after radiopharmaceutical injection.
METHODS: A total of 33 patients undergoing treatment or in post-treatment follow-up for medication-related osteonecrosis of the jaw, who visited our hospital between July 2020 and August 2021 and could receive SPECT twice on the same day, were enrolled in the study. Patients were injected with technetium-99 m hydroxymethylene diphosphonate (Tc-99 m HMDP) intravenously. The SUVmax for healthy parietal bones and jawbone lesions were calculated from the SPECT images using quantitative analysis software, and the SUVmax were compared between 2- and 3-hour uptake times.
RESULTS: After exclusion, 30 patients were included in the study. In the 2-hour and 3-hour images, the median SUVmax of the parietal bones were 1.90 and 1.81, respectively, and those of the jawbone lesions were 9.25 and 9.39, respectively. The limits of agreement (LOA) ranged from - 0.33 to 0.25 in the parietal bones, and the %LOA ranged from - 9.8 to 17.3% in the jawbone lesions, showing high equivalence between the two uptake durations. The SUVmax showed no clinical differences between the 2- and 3-hour uptake durations for Tc-99 m HMDP SPECT of the jawbone.
CONCLUSIONS: The results of this study justify a 2-3-hour uptake window when performing quantitative SPECT of the jawbone. Therefore, the minimum uptake time can potentially be reduced to only 2 hours.

The aim of this study was to investigate the jawbone concentration of clindamycin (CLI) in patients with an osteonecrosis of the jaw (ONJ). Patients with medication-related ONJ (MRONJ) and osteoradionecrosis (ORN) with an antibiotic treatment with CLI were included. Plasma, vital and necrotic bone samples were collected. Plasma and jawbone samples were analyzed by liquid chromatography-tandem mass spectrometry. Patients with MRONJ exhibited a mean plasma CLI concentration of 9.6 μg/mL (SD ± 3.6 μg/mL) and mean concentrations of 2.3 μg/g CLI (SD ± 1.4 μg/g) and 2.1 μg/g CLI (SD ± 2.4 μg/g) in vital and necrotic bone samples, without statistical significance (p = 0.79). In patients with ORN, mean concentration in plasma was 12.0 μg/mL (SD ± 2.6 μg/mL), in vital bone 2.1 μg/g (SD ± 1.5 μg/g), and in necrotic bone 1.7 μg/g (SD ± 1.2 μg/g). Vital and necrotic bone concentrations did not differ significantly (p = 0.88). The results demonstrate that CLI concentrations are considerably lower than in plasma, but sufficient for most bacteria present in ONJ. Within the limitations of the study, it seems that CLI is a relevant alternative to other antibiotics in the treatment of ONJ because it reaches adequate concentrations in jawbone.

OBJECTIVE: Recent research has demonstrated that platelet-rich fibrin (PRF) is an appropriate carrier for ampicillin/sulbactam. The aim of the study was to investigate whether PRF is also a suitable bio-carrier for clindamycin (CLI).
METHODS: PRF membranes were produced from 36 patients receiving intravenous therapy with CLI (e.g. due to the diagnosis of an osteonecrosis of the jaw or infections). Concentrations of CLI in PRF membranes were measured with liquid chromatography-tandem mass spectrometry, and the antimicrobial effects were investigated in vitro in agar diffusion tests with fresh PRF and PRF stored for 24 h. Storage was performed in an incubator at 36 °C to simulate the in-vivo situation.
RESULTS: The mean concentration of CLI in plasma was 1.0 ± 0.3 μg/100 mg plasma; in resulting PRF membranes 0.7 ± 0.4 μg/100 mg PRF. Agar diffusion tests were performed with Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus mitis, Porphyromonas gingivalis, and Fusobacterium nucleatum. Mean inhibition zones, in mm, for fresh PRF were 17.3, 12.2, 18.8, 17.1, 25.8 and 18.1, 12.7, 19.2, 17.3, and 26.3 for stored PRF, respectively.
CONCLUSIONS: The results demonstrate that PRF is a suitable bio-carrier for CLI when administered systemically to patients. The concentration in PRF generated from patients after infusion of 600 mg CLI dose suffices to target clinically relevant bacteria.
CONCLUSIONS: Using PRF as a carrier for local antibiotic application can prevent infections in oral and maxillofacial surgery. Within the study limitations, the findings could expand the scope of PRF application by adding CLI as a new antibiotic to the spectrum of PRF therapy.

Upper limb lymphedema (ULLy) is an external (and/or internal) manifestation of lymphatic system insufficiency and deranged lymph transport for more than 3 months and frequently affects people as a consequence of breast cancer (BC). ULLy is often underestimated despite diminished motor skills, mood, and cognitive-behavioral complaints negatively condition the health-related quality of life (HRQoL) of persons. BC can also metastasize to the jawbone, further impacting on the HRQoL. In time, the implementation of robot-assisted rehabilitation (RR) for neurological diseases has grown to improve HRQoL and pain. This study aims to evaluate the effectiveness of a RR program in the treatment of individuals who develop an ULLy; as a further analysis, the study will assess the effectiveness of the same program in people with jawbone metastases from BC who will also develop ULLy. A randomized, parallel-group superiority-controlled trial will be conducted. 44 participants will be randomly allocated to either the experimental (receiving a RR program) or the control group (regular rehabilitation). Both groups will follow individual-based programs three times a week for 10 weeks. The main outcome measure will be the Lymphedema Quality of Life Questionnaire. Secondary outcomes will be a pain intensity numerical rating scale and the Cranio-Facial Pain Disability Inventory. Evaluations are before and after training and 6 months later. Findings may provide evidence on the effectiveness of a RR program on inducing improvements in the HRQoL and pain of individuals with ULLy due to BC. People with ULLy and jawbone metastases from BC are expected for similar or higher improvements as per the same comparisons above. This trial might contribute towards defining guidelines for good clinical rehabilitation routines and might be used as a basis for health authorities\' endorsements.Trial registration OSF REGISTRIES, osf-registrations-jz7ax-v1 . Registered on 26 June 2023.