-
Amino Acids Jun 2024Exogenous polyamines, including putrescine (PUT), spermidine (SPD), and spermine (SPM), and the irreversible inhibitor of the rate-limiting enzyme ornithine...
Exogenous polyamines, including putrescine (PUT), spermidine (SPD), and spermine (SPM), and the irreversible inhibitor of the rate-limiting enzyme ornithine decarboxylase (ODC) of polyamine biosynthesis, α-difluoromethylornithine (DFMO), are implicated as stimulants for bone formation. We demonstrate in this study the osteogenic potential of exogenous polyamines and DFMO in human osteoblasts (hOBs), murine monocyte cell line RAW 264.7, and an ovariectomized rat model. The effect of polyamines and DFMO on hOBs and RAW 264.7 cells was studied by analyzing gene expression, alkaline phosphatase (ALP) activity, tartrate-resistant acid phosphatase (TRAP) activity, and matrix mineralization. Ovariectomized rats were treated with polyamines and DFMO and analyzed by micro computed tomography (micro CT). The mRNA level of the early onset genes of osteogenic differentiation, Runt-related transcription factor 2 (Runx2) and ALP, was significantly elevated in hOBs under osteogenic conditions, while both ALP activity and matrix mineralization were enhanced by exogenous polyamines and DFMO. Under osteoclastogenic conditions, the gene expression of both receptor activator of nuclear factor-κB (RANK) and nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) was reduced, and TRAP activity was suppressed by exogenous polyamines and DFMO in RAW 264.7 cells. In an osteoporotic animal model of ovariectomized rats, SPM and DFMO were found to improve bone volume in rat femurs, while trabecular thickness was increased in all treatment groups. Results from this study provide in vitro and in vivo evidence indicating that polyamines and DFMO act as stimulants for bone formation, and their osteogenic effect may be associated with the suppression of osteoclastogenesis.
Topics: Animals; Mice; Osteoclasts; Osteogenesis; Rats; Humans; Cell Differentiation; Eflornithine; Female; Polyamines; Osteoblasts; RAW 264.7 Cells; Ovariectomy; Rats, Sprague-Dawley; Spermidine
PubMed: 38935136
DOI: 10.1007/s00726-024-03403-8 -
Oral Diseases Jun 2024The purpose of this study was to determine whether indoxyl sulfate (IS) is involved in alveolar bone deterioration and to elucidate the mechanism underlying alveolar...
OBJECTIVES
The purpose of this study was to determine whether indoxyl sulfate (IS) is involved in alveolar bone deterioration and to elucidate the mechanism underlying alveolar bone loss in chronic kidney disease (CKD) patients.
MATERIALS AND METHODS
Mice were divided into the control group, CP group (ligature-induced periodontitis), CKD group (5/6 nephrectomy), and CKD + CP group. The concentration of IS in the gingival crevicular fluid (GCF) was determined by HPLC. The bone microarchitecture was evaluated by micro-CT. MC3T3-E1 cells were stimulated with IS, and changes in mitochondrial morphology and ferroptosis-related factors were detected. RT-PCR, western blotting, alkaline phosphatase activity assays, and alizarin red S staining were utilized to assess how IS affects osteogenic differentiation.
RESULTS
Compared with that in the other groups, alveolar bone destruction in the CKD + CP group was more severe. IS accumulated in the GCF of mice with CKD. IS activated the aryl hydrocarbon receptor (AhR) in vitro, inhibited MC3T3-E1 cell osteogenic differentiation, caused changes in mitochondrial morphology, and activated the SLC7A11/GPX4 signaling pathway. An AhR inhibitor attenuated the aforementioned changes induced by IS.
CONCLUSIONS
IS activated the AhR/SLC7A11/GPX4 signaling pathway, inhibited osteogenesis in MC3T3-E1 cells, and participated in alveolar bone resorption in CKD model mice through ferroptosis.
PubMed: 38934473
DOI: 10.1111/odi.15050 -
Pharmaceutics May 2024Alternative therapies associating natural products and nanobiotechnology show new perspectives on controlled drug release. In this context, nanoemulsions (NEs) present...
Alternative therapies associating natural products and nanobiotechnology show new perspectives on controlled drug release. In this context, nanoemulsions (NEs) present promising results for their structural design and properties. Hesperetin (HT), a flavonoid mainly found in citrus fruits, presents highlighted bone benefits. In this context, we developed a hesperetin-loaded nanoemulsion (HT-NE) by sonication method and characterized it by dynamic light scattering, analyzing its encapsulation efficiency, and cumulative release. The biocompatibility in human osteoblasts Saos-2-like was evaluated by the cytotoxicity assay and IC. Then, the effects of the HT-NE on osteogenesis were evaluated by the cellular proliferation, calcium nodule formation, bone regulators gene expression, collagen quantification, and alkaline phosphatase activity. The results showed that the formulation presented ideal values of droplet size, polydispersity index, and zeta potential, and the encapsulation efficiency was 74.07 ± 5.33%, showing a gradual and controlled release. Finally, HT-NE was shown to be biocompatible and increased cellular proliferation, and calcium nodule formation, regulated the expression of , , and genes, and increased the collagen formation and alkaline phosphatase activity. Therefore, the formulation of this NE encapsulated the HT appropriately, allowing the increasing of its effects on mechanisms to improve or accelerate the osteogenesis process.
PubMed: 38931821
DOI: 10.3390/pharmaceutics16060698 -
Nutrients Jun 2024A balanced diet rich in calcium and protein is recommended for bone-healthy people and osteoporosis patients, but it may also be important for rare bone disease (RBD)....
BACKGROUND
A balanced diet rich in calcium and protein is recommended for bone-healthy people and osteoporosis patients, but it may also be important for rare bone disease (RBD). Little data is available on RBD and diet. Therefore, the aim of this study was to evaluate the nutritional behavior of patients with RBD.
METHODS
This single-center, cross-sectional, questionnaire-based study assessed the nutritional behavior of RBD patients (X-linked hypophosphatemia (XLH), osteogenesis imperfecta (OI), hypophosphatasia (HPP)), osteoporosis (OPO) patients and healthy controls (CTRL). The nutritional questionnaire comprised 25 questions from seven nutritional areas. The associations between socioeconomic factors and BMI were assessed by age-adjusted univariate analysis of covariance (ANCOVA).
RESULTS
Fifty patients with RBD (17 OI, 17 HPP, 16 XLH; mean age of 48.8 ± 15.9, 26.0% male, mean BMI 26.2 ± 5.6), 51 with OPO (mean age 66.6 ± 10.0, 9.8% male, mean BMI 24.2 ± 3.9) and 52 CTRL (mean age 50.8 ± 16.3, 26.9% male, mean BMI 26.4 ± 4.7) participated. Twenty-six (52.0%) RBD, 17 (33.4%) OPO and 24 (46.1%) CTRL were overweight or obese according to BMI. Only a minority of RBD, OPO and CTRL had a daily intake of at least three portions of milk or milk products (17.3% RBD, 15.6% OPO, 11.6% CTRL, = 0.453). In general, similar nutritional behavior was observed between the three subgroups. However, significant differences were found in caffeine consumption ( = 0.016), fruit/vegetable juice consumption ( = 0.034), portions of fish per week ( = 0.044), high-fat meals per week ( = 0.015) and consumption of salty snacks ( = 0.001).
CONCLUSION
Nutritional counseling, controlling BMI and ensuring sufficient calcium and protein intake are crucial in patients with osteoporosis as well as in rare bone diseases. Vitamin D does not appear to be sufficiently supplied by the diet, and therefore supplementation should be considered in patients with bone diseases.
Topics: Humans; Cross-Sectional Studies; Male; Female; Middle Aged; Austria; Adult; Aged; Bone Diseases; Surveys and Questionnaires; Body Mass Index; Osteoporosis; Feeding Behavior; Nutritional Status; Diet
PubMed: 38931274
DOI: 10.3390/nu16121920 -
Journal of Clinical Medicine Jun 2024: Defects of the ascending ramus of the mandible, including the condylar head and neck or the whole temporomandibular joint (TMJ), are difficult to reconstruct....
: Defects of the ascending ramus of the mandible, including the condylar head and neck or the whole temporomandibular joint (TMJ), are difficult to reconstruct. Reconstruction is mainly based on the use of alloplastic joint prosthesis, costochondral grafting, distraction osteogenesis of the dorsal part of the mandibular ramus, or osseous microvascular flaps of various origin. With the objective of developing a method that overcomes the restrictions of these methods, we recently introduced a sequential chimeric flap consisting of a lateral femoral condyle flap (LFC) and deep circumflex iliac artery flap (DCIA) for reconstruction of up to half of the mandible and the condylar head and neck. : The chimeric flap was used in four patients with the following diagnoses: therapy-refractory osteomyelitis, extended recurrent odontogenic keratozyst, Goldenhar syndrome, and adenocarcinoma of the parotid gland. After a diagnostic workup, LFC and DCIA flaps were harvested in all patients and used in a sequential chimeric design for the reconstruction of the mandibular body and condylar head and neck. : Follow-up from at least 24 months up to 70 month after surgery showed a successful reconstruction in all four patients. The LFC provided a cartilaginous joint surface, allowing for a satisfactory masticatory function with a stable occlusion and unrestricted mouth opening and preserved or regained lateral and medial excursions in all patients. The DCIA allowed for a bony reconstruction anatomically resembling a non-atrophied mandibular body. No flap-related complications were observed. : The sequential chimeric LFC and DCIA flap is an appropriate method for reconstructing up to half of the mandible and the condylar head and neck. It is suitable in cases where alloplastic joint replacement cannot be used or where other methods have failed. Due to the necessity of harvesting two flaps, the burden of care is increased, and a careful indication is required. The technique is reserved for maxillofacial surgeons who have already gained significant experience in the field of microsurgery.
PubMed: 38930140
DOI: 10.3390/jcm13123613 -
Journal of Clinical Medicine Jun 2024Osteogenesis Imperfecta (OI) is a genetic disorder caused by mutations in genes responsible for collagen synthesis or polypeptides involved in the formation of collagen... (Review)
Review
Osteogenesis Imperfecta (OI) is a genetic disorder caused by mutations in genes responsible for collagen synthesis or polypeptides involved in the formation of collagen fibers. Its predominant skeletal complication is scoliosis, impacting 25 to 80% of OI patients. Vertebral deformities of the scoliotic curves in OI include a variety of malformations such as codfish, wedged-shaped vertebrae or platyspondyly, craniocervical junction abnormalities, and lumbosacral spondylolysis and spondylolisthesis. Although the precise pathophysiology of these spinal deformities remains unclear, anomalies in bone metabolism have been implicated in the progression of scoliotic curves. Bone Mineral Density (BMD) measurements have demonstrated a significant reduction in the Z-score, indicating osteoporosis and a correlation with the advancement of scoliosis. Factors such as increased mechanical strains, joint hypermobility, lower leg length discrepancy, pelvic obliquity, spinal ligament hypermobility, or vertebrae microfractures may also contribute to the severity of scoliosis. Histological vertebral analysis has confirmed that changes in trabecular microarchitecture, associated with inadequate bone turnover, indicate generalized bone metabolic defects in OI. At the molecular level, the upregulation of Transforming Growth factor-β (TGFβ) signaling in OI can lead to disturbed bone turnover and changes in muscle mass and strength. Understanding the relationship between spinal clinical features and molecular pathways could unveil TGFβ -related molecular targets, paving the way for novel therapeutic approaches in OI.
PubMed: 38930011
DOI: 10.3390/jcm13123484 -
International Journal of Molecular... Jun 2024Bone regeneration involves multiple factors such as tissue interactions, an inflammatory response, and vessel formation. In the event of diseases, old age, lifestyle, or... (Review)
Review
Bone regeneration involves multiple factors such as tissue interactions, an inflammatory response, and vessel formation. In the event of diseases, old age, lifestyle, or trauma, bone regeneration can be impaired which could result in a prolonged healing duration or requiring an external intervention for repair. Currently, bone grafts hold the golden standard for bone regeneration. However, several limitations hinder its clinical applications, e.g., donor site morbidity, an insufficient tissue volume, and uncertain post-operative outcomes. Bone tissue engineering, involving stem cells seeded onto scaffolds, has thus been a promising treatment alternative for bone regeneration. Adipose-derived mesenchymal stem cells (AD-MSCs) are known to hold therapeutic value for the treatment of various clinical conditions and have displayed feasibility and significant effectiveness due to their ease of isolation, non-invasive, abundance in quantity, and osteogenic capacity. Notably, in vitro studies showed AD-MSCs holding a high proliferation capacity, multi-differentiation potential through the release of a variety of factors, and extracellular vesicles, allowing them to repair damaged tissues. In vivo and clinical studies showed AD-MSCs favoring better vascularization and the integration of the scaffolds, while the presence of scaffolds has enhanced the osteogenesis potential of AD-MSCs, thus yielding optimal bone formation outcomes. Effective bone regeneration requires the interplay of both AD-MSCs and scaffolds (material, pore size) to improve the osteogenic and vasculogenic capacity. This review presents the advances and applications of AD-MSCs for bone regeneration and bone tissue engineering, focusing on the in vitro, in vivo, and clinical studies involving AD-MSCs for bone tissue engineering.
Topics: Bone Regeneration; Humans; Mesenchymal Stem Cells; Adipose Tissue; Animals; Mesenchymal Stem Cell Transplantation; Tissue Engineering; Tissue Scaffolds; Osteogenesis; Cell Differentiation
PubMed: 38928517
DOI: 10.3390/ijms25126805 -
International Journal of Molecular... Jun 2024Our skeleton is an essential part of our body consisting of 206 pieces made of a specialized form of connective tissue, with a matrix containing collagen fibers and a...
Our skeleton is an essential part of our body consisting of 206 pieces made of a specialized form of connective tissue, with a matrix containing collagen fibers and a large amount of minerals [...].
Topics: Humans; Bone Development; Animals; Bone and Bones; Osteogenesis
PubMed: 38928471
DOI: 10.3390/ijms25126767 -
International Journal of Molecular... Jun 2024Osteoporosis, a prevalent chronic health issue among the elderly, is a global bone metabolic disease. Flavonoids, natural active compounds widely present in vegetables,...
Onion ( L.) Flavonoid Extract Ameliorates Osteoporosis in Rats Facilitating Osteoblast Proliferation and Differentiation in MG-63 Cells and Inhibiting RANKL-Induced Osteoclastogenesis in RAW 264.7 Cells.
Osteoporosis, a prevalent chronic health issue among the elderly, is a global bone metabolic disease. Flavonoids, natural active compounds widely present in vegetables, fruits, beans, and cereals, have been reported for their anti-osteoporotic properties. Onion is a commonly consumed vegetable rich in flavonoids with diverse pharmacological activities. In this study, the trabecular structure was enhanced and bone mineral density (BMD) exhibited a twofold increase following oral administration of onion flavonoid extract (OFE). The levels of estradiol (E2), calcium (Ca), and phosphorus (P) in serum were significantly increased in ovariectomized (OVX) rats, with effects equal to alendronate sodium (ALN). Alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) levels in rat serum were reduced by 35.7% and 36.9%, respectively, compared to the OVX group. In addition, the effects of OFE on bone health were assessed using human osteoblast-like cells MG-63 and osteoclast precursor RAW 264.7 cells in vitro as well. Proliferation and mineralization of MG-63 cells were promoted by OFE treatment, along with increased ALP activity and mRNA expression of osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL). Additionally, RANKL-induced osteoclastogenesis and osteoclast activity were inhibited by OFE treatment through decreased TRAP activity and down-regulation of mRNA expression-related enzymes in RAW 264.7 cells. Overall findings suggest that OFE holds promise as a natural functional component for alleviating osteoporosis.
Topics: Animals; Osteoblasts; RANK Ligand; Osteoporosis; Flavonoids; Mice; Onions; Cell Differentiation; Plant Extracts; Rats; Cell Proliferation; RAW 264.7 Cells; Osteogenesis; Humans; Female; Osteoclasts; Bone Density; Ovariectomy; Rats, Sprague-Dawley; Osteoprotegerin
PubMed: 38928460
DOI: 10.3390/ijms25126754 -
International Journal of Molecular... Jun 2024Natural products have attracted great interest in the development of tissue engineering. Recent studies have demonstrated that unsaturated fatty acids found in natural...
Natural products have attracted great interest in the development of tissue engineering. Recent studies have demonstrated that unsaturated fatty acids found in natural plant seed oil may exhibit positive osteogenic effects; however, few in vivo studies have focused on the use of plant seed oil for bone regeneration. The aim of this study is to investigate the effects of seed oil found in () on the osteogenic differentiation of mesenchymal stem cells and bone growth in artificial bone defects in vivo. In this study, Wharton-jelly-derived mesenchymal stem cells (WJMSCs) were co-cultured with seed oil. Cellular osteogenic capacity was assessed using Alizarin Red S staining. Real-time PCR was carried out to evaluate ALP and OCN gene expression. The potential of seed oil to enhance bone growth was assessed using an animal model. Four 6 mm circular defects were prepared at the parietal bone of New Zealand white rabbits. The defects were filled with hydrogel and hydrogel- seed oil, respectively. Quantitative analysis of micro-computed tomography (Micro-CT) and histological images was conducted to compare differences in osteogenesis between oil-treated and untreated samples. Although our results showed no significant differences in viability between WJMSCs treated with and without seed oil, under osteogenic conditions, seed oil facilitated an increase in mineralized nodule secretion and upregulated the expression of ALP and OCN genes in the cells ( < 0.05). In the animal study, both micro-CT and histological evaluations revealed that new bone formation in artificial bone defects treated with seed oil were nearly doubled compared to control defects ( < 0.05) after 4 weeks of healing. Based on these findings, it is reasonable to suggest that seed oil holds promise as a potential candidate for enhancing bone healing efficiency in bone tissue engineering.
Topics: Animals; Rabbits; Plant Oils; Seeds; Mesenchymal Stem Cells; Osteogenesis; Bone Regeneration; Sapindus; Cell Differentiation; X-Ray Microtomography; Tissue Engineering; Humans; Cells, Cultured
PubMed: 38928455
DOI: 10.3390/ijms25126749