Osteocyte Apoptosis, Bone Marrow Adiposity, and Fibrosis in the Irradiated Human Mandible

Dekker, Hannah; Schulten, E.A.J.M.; Lichters, I.; Ruijven, Leo van; Essen, H.W. van; Blom, Gerrit J.; Bloemena, Elisabeth; Bruggenkate, Chr.M. ten; Kullaa, Arja; Bravenboer, E.N.

doi:10.1016/j.adro.2022.100951

Cited by 9 publications

(9 citation statements)

References 56 publications

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“…This further increases bone fragility, making bones more likely to fracture, destroying bone microstructure, and reducing bone mineral density and quality [ 39 , 40 ]. While there are two types of osteoporosis, primary and secondary [ 41 ], bone marrow adipocytes and osteoblasts also develop from MSCs [ 42 ]. The quantity of MSCs that have differentiated into osteoblasts would decrease due to the aberrant rise in adipocytes in the bone marrow [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Melatonin Repairs Osteoporotic Bone Defects in Iron-Overloaded Rats through PI3K/AKT/GSK-3β/P70S6k Signaling Pathway

Ren

Liu

Jiang

et al. 2023

Oxidative Medicine and Cellular Longevity

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It was found recently that iron overload can cause osteoporosis in rats. Through in vitro and in vivo experimentations, the purpose of the present study was to validate and confirm the inhibitory effects of melatonin on iron death of osteoporosis and its role in bone microstructure improvements. Melatonin (100 mol/L) was administered to MC3T3-E1 cells induced by iron overload in vitro for 48 hours. The expression of cleaved caspase-3 and cleaved PARP and the production of ROS (reactive oxygen species) and mitochondrial damage were all exacerbated by iron overload. On the other hand, melatonin restored these impacts in MC3T3-E1 cells produced by iron overload. By evaluating the expression of PI3K/AKT/GSK-3β/P70S6k signaling pathway-related proteins (RUNX2, BMP2, ALP, and OCN) using RT-PCR and Western blot, osteogenic-related proteins were identified. Alizarin red S and alkaline phosphatase were utilized to evaluate the osteogenic potential of MC3T3-E1 cells. Melatonin significantly improved the osteogenic ability and phosphorylation rates of PI3K, AKT, GSK-3β, and P70S6k in iron overload-induced MC3T3-E1 cells. In vivo, melatonin treated iron overload-induced osteoporotic bone defect in rats. Rat skeletal microstructure was observed using micro-CT and bone tissue pathological section staining. ELISA was utilized to identify OCN, PINP, CTX-I, and SI in the serum of rats. We discovered that melatonin increased bone trabecular regeneration and repair in osteoporotic bone defects caused by iron overload. In conclusion, melatonin enhanced the osteogenic ability of iron overload-induced MC3T3-E1 cells by activating the PI3K/AKT/GSK-3β/P70S6k signaling pathway and promoting the healing of iron overload-induced osteoporotic bone defects in rats.

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Section: Discussionmentioning

confidence: 99%

Melatonin Repairs Osteoporotic Bone Defects in Iron-Overloaded Rats through PI3K/AKT/GSK-3β/P70S6k Signaling Pathway

Ren

Liu

Jiang

et al. 2023

Oxidative Medicine and Cellular Longevity

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“…A previously described protocol for immunostaining was used 28,29,34 . To visualize and calculate the number of apoptotic osteocytes, immunohistochemical staining for Cleaved Caspase‐3 was carried out on a subset of biopsies ( n = 6).…”

Section: Methodsmentioning

confidence: 99%

“…A previously described protocol for immunostaining was used. 28 , 29 , 34 To visualize and calculate the number of apoptotic osteocytes, immunohistochemical staining for Cleaved Caspase‐3 was carried out on a subset of biopsies ( n = 6). Receptor activator of nuclear factor‐κB ligand (RANKL) expression by osteocytes was also detected by immunohistochemistry on a subset of biopsies ( n = 6).…”

Section: Methodsmentioning

confidence: 99%

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Bone vitality and vascularization of mandibular and maxillary bone grafts in maxillary sinus floor elevation: A retrospective cohort study

Schulten

Helder

et al. 2022

Clin Implant Dent Rel Res

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Objectives Mandibular retromolar (predominantly cortical) and maxillary tuberosity (predominantly cancellous) bone grafts are used in patients undergoing maxillary sinus floor elevation (MSFE) for dental implant placement. The aim of this retrospective cohort study was to investigate whether differences exist in bone formation and vascularization after grafting with either bone source in patients undergoing MSFE. Methods Fifteen patients undergoing MSFE were treated with retromolar (n = 9) or tuberosity (n = 6) bone grafts. Biopsies were taken 4 months postoperatively prior to dental implant placement, and histomorphometrically analyzed to quantify bone and osteoid area, number of total, apoptotic, and receptor activator of nuclear factor‐κB ligand (RANKL)‐positive osteocytes, small and large‐sized blood vessels, and osteoclasts. The grafted area was divided in three regions (caudal‐cranial): RI, RII, and RIII. Results Bone volume was 40% (RII, RIII) higher and osteoid volume 10% (RII) lower in retromolar compared to tuberosity‐grafted areas. Total osteocyte number and number of RANKL‐positive osteocytes were 23% (RII) and 90% (RI, RII) lower, but osteoclast number was higher (retromolar: 12, tuberosity: 0) in retromolar‐grafted areas. The total number of blood vessels was 80% (RI) to 60% (RIII) lower, while the percentage of large‐sized blood vessels was 86% (RI) to 25% (RIII) higher in retromolar‐grafted areas. Number of osteocyte lacunae and apoptotic osteocytes were similar in both bone grafts used. Conclusions Compared to the retromolar bone, tuberosity bone showed increased bone vitality and vascularization in patients undergoing MSFE, likely due to faster bone remodeling or earlier start of new bone formation. Therefore, tuberosity bone grafts might perform better in enhancing bone regeneration.

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“…Quantitatively, RCI significantly decreased the production in megakaryocytes (Figure 4B). As a consequence, the marrow was replaced by adipocytes (Figure 4C) in the RCI groups, since an increase in the adipocyte number in BM is secondary to a decrease in hematopoietic cells [21,[39][40][41][42]. Histological images (Figure 4A) demonstrated that the RCI with doses ranging from 8.5 Gy to 9.5 Gy induced the BM hypocellularity to a similar degree of severity, which was confirmed by no apparent dose responses in the quantification of megakaryocytes and adipocytes (Figure 4B,C).…”

Section: Rci With Doses Ranging From 85 Gy To 95 Gy Induces Hypocellu...mentioning

confidence: 99%

Deteriorative Effects of Radiation Injury Combined with Skin Wounding in a Mouse Model

Wang

Lin

Zhai

et al. 2022

Toxics

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Radiation-combined injury (RCI) augments the risk of morbidity and mortality when compared to radiation injury (RI) alone. No FDA-approved medical countermeasures (MCMs) are available for treating RCI. Previous studies implied that RI and RCI elicit differential mechanisms leading to their detrimental effects. We hypothesize that accelerating wound healing improves the survival of RCI mice. In the current study, we examined the effects of RCI at different doses on lethality, weight loss, wound closure delay, and proinflammatory status, and assessed the relative contribution of systemic and local elements to their delayed wound closure. Our data demonstrated that RCI increased the lethality and weight loss, delayed skin wound closure, and induced a systemic proinflammatory status in a radiation dose-dependent manner. We also demonstrated that delayed wound closure did not specifically depend on the extent of hematopoietic suppression, but was significantly influenced by the toxicity of the radiation-induced systemic inflammation and local elements, including the altered levels of proinflammatory chemokines and factors, and the dysregulated collagen homeostasis in the wounded area. In conclusion, the results from our study indicate a close association between delayed wound healing and the significantly altered pathways in RCI mice. This insightful information may contribute to the evaluation of the prognosis of RCI and development of MCMs for RCI.

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Osteocyte Apoptosis, Bone Marrow Adiposity, and Fibrosis in the Irradiated Human Mandible

Cited by 9 publications

References 56 publications

Melatonin Repairs Osteoporotic Bone Defects in Iron-Overloaded Rats through PI3K/AKT/GSK-3β/P70S6k Signaling Pathway

Melatonin Repairs Osteoporotic Bone Defects in Iron-Overloaded Rats through PI3K/AKT/GSK-3β/P70S6k Signaling Pathway

Bone vitality and vascularization of mandibular and maxillary bone grafts in maxillary sinus floor elevation: A retrospective cohort study

Deteriorative Effects of Radiation Injury Combined with Skin Wounding in a Mouse Model

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