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Oral supplementation with Lactiplantibacillus plantarum 6.2 in rats enhances bone and epithelial tissue repair by inhibiting NF-κB protein and promoting extracellular matrix synthesis via TGF-β.

BACKGROUND: This study aimed to investigate the healing and anti-inflammatory potential of the Lactiplantibacillus plantarum 6.2 (Lp62) strain, administered orally in a murine model of medication-related osteonecrosis of the jaw (MRONJ). MATERIALS AND METHODS: Twenty male Wistar rats (N = 20) were randomly assigned to four groups (n = 5 per group): negative control (BASAL), healthy rats supplemented with Lp62 (LAC), experimental osteonecrosis (ONE), and osteonecrosis supplemented with Lp62 (ONE+LAC). Over an 8-week period, MRONJ was induced by intraperitoneal injections of zoledronic acid (25

Preclinical assessment of leukocyte- and platelet-rich fibrin for inhibition of mandibular osteonecrosis.

Considering that osteonecrosis of the jaw may be due to the antiangiogenic effect of bisphosphonates and that leukocyte- and platelet-rich fibrin (L-PRF) releases proangiogenic factors, this study hypothesized that L-PRF could prevent mandibular osteonecrosis in the surgical alveoli of rats treated with sodium alendronate (ALE) or zoledronic acid (ZOL). A sample of 42 male Holtzman rats aged 3 months was divided into 3 experimental groups receiving different forms of treatment (n = 14): ALE, 1 mg/mL/kg weekly; ZOL, 0.3 mg/mL/kg weekly; or saline solution as a control vehicle, 0.009 mg/mL/kg we

3D-Printed and Biofabricated Scaffolds for Osteoporotic Bone Defect Repair: Mechanical Adaptation, Redox Control, Senescence Modulation and Osteoimmunomodulation.

Fragility fracture and osteoporotic bone loss represent an increasing global burden in ageing populations: the Global Burden of Disease Study 2021 estimated 172.79 million new fractures, 453.31 million prevalent cases, and 25.18 million years lived with disability in 2021, yet the resulting defects are still managed with grafts and scaffolds validated in healthy bone. Osteoporotic bone is not merely rarefied normal bone but a distinct regenerative microenvironment, in which we propose that oxidative stress, cellular senescence, and loss of osteogenesis-coupled type-H vasculature act as a mutua

Altered bone structure in Niemann-Pick Type C1 mice, especially in females.

Niemann-Pick type C disease (NPC) is a rare lysosomal storage disorder belonging to the group of sphingolipidoses and is caused by a genetic defect affecting cholesterol trafficking. Since other sphingolipidoses with lipid accumulations show disrupt bone, this study investigated bone structure in an Npc1 mouse model and assessed whether pharmacological treatments (miglustat, 2-hydroxypropyl-β-cyclodextrin [HPßCD], and combination therapy including allopregnanolone) affected it. Femora from Npc1-/- mice of postnatal day (P) 65 were analysed using histology, histomorphometry and micro-CT. Additi

Impact of Myb deficiency on Rankl/Opg expression within the developing mouse mandible.

The Rank-Rankl-Opg axis is a fundamental regulatory triad in bone development and remodelling. While extensively studied, novel modulators of this system continue to emerge, with the transcription factor Myb recently gaining attention due to its unexpected presence and physiological significance in tooth and bone, beyond its well-established role in haematopoiesis. To establish a baseline for normal development, we first elucidated the developmental dynamics of Rankl and Opg expression during prenatal mandibular development and osteocytogenesis in wild-type mice within distinct morphological r

Nrf2 signaling in bone health: unlocking new avenues for osteoporosis management.

Osteoporosis (OP) is a progressive skeletal disorder characterized by reduced bone mass, structural deterioration, and increased fracture risk, particularly in postmenopausal women and the elderly. Oxidative stress and inflammation are key contributors to the disruption of bone remodeling in OP. Nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of cellular redox homeostasis, has gained attention for its role in bone metabolism. This review explores Nrf2's regulatory influence on osteoblast (OB) and osteoclast (OC) activity. In OBs, moderate Nrf2 activation protects against

Analysis of Risedronate Analog on Extraction Socket Healing in Mice.

BACKGROUND/AIM: Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse effect associated with anti-resorptive medications like nitrogen-containing bisphosphonates (N-BPs), particularly zoledronate (ZOL). This study aimed to investigate whether a BP analog with high bone affinity but minimal anti-resorptive activity, NE-58051, could induce MRONJ-like lesions in a mouse model. MATERIALS AND METHODS: Female C57BL/6J mice (n=6 per group) were administered ZOL (250 μg/kg intravenously, twice weekly) for one or two weeks, or NE-58051 (250 μg/kg intravenously, twice weekly) for two

Cranial bone microarchitecture in a mouse model for syndromic craniosynostosis.

Crouzon syndrome is a congenital craniofacial disorder caused by mutations in the Fibroblast Growth Factor Receptor 2 (FGFR2). It is characterized by the premature fusion of cranial sutures, leading to a brachycephalic head shape, and midfacial hypoplasia. The aim of this study was to investigate the effect of the FGFR2 mutation on the microarchitecture of cranial bones at different stages of postnatal skull development, using the FGFR2C342Y mouse model. Apart from craniosynostosis, this model shows cranial bone abnormalities. High-resolution synchrotron microtomography images of the frontal a

Initial therapeutic evidence of a borosilicate bioactive glass (BSG) and Fe3O4 magnetic nanoparticle scaffold on implant-associated Staphylococcal aureus bone infection.

Implant-associated Staphylococcus aureus (S. aureus) osteomyelitis is a severe challenge in orthopedics. While antibiotic-loaded bone cement is a standardized therapeutic approach for S. aureus osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (Fe3O4) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities. We conducted comprehensive asse

Preoperative Assessment of Medication-Related Osteonecrosis of the Jaw Using [18F]fluoride Positron Emission Tomography (PET)/CT and [18F]fluorodeoxyglucose PET/MRI in Correlation with Histomorphometry and Micro-CT-A Prospective Comparative Study.

OBJECTIVES: The purpose of this study was to investigate the imaging characteristics of medication-related osteonecrosis of the jaw (MRONJ) using [18F]fluoride positron emission tomography/computed tomography (PET/CT) and [18F]fluorodeoxyglucose (FDG) PET/magnetic resonance imaging (MRI) for preoperative assessment and to correlate them with microarchitectural and histomorphometric data with respect to clinical findings. METHODS: Twelve patients (five female; mean age 75 ± 7.6 yr) with symptomatic MRONJ underwent both scans on the same day, and imaging findings were used to plan surgical inte

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… Histomorphometry The osteocyte density differed significantly among the groups ( Table 4 ). … The bone with the highest [18F]fluoride uptake had the highest osteocyte density (335.5 cells/mm 2 ), followed by the bone with medium hot uptake (164.4 cells/mm 2 ), and the necrotic bone had the lowest osteocyte density, as expected, with the absence of osteocytes in the lacunae. …

The DLEU2-miR-15a-16-1 Cluster Is a Determinant of Bone Microarchitecture and Strength in Postmenopausal Women and Mice.

This study explores how select microRNAs (miRNAs) influence bone structure in humans and in transgenic mice. In trabecular bone biopsies from 84 postmenopausal women (healthy, osteopenic, and osteoporotic), we demonstrate that DLEU2 (deleted in lymphocytic leukemia 2)-encoded miR-15a-5p is strongly positively associated with bone mineral density (BMD) at different skeletal sites. In bone transcriptome analyses, miR-15a-5p levels correlated positively with the osteocyte characteristic transcripts SOST (encoding sclerostin) and MEPE (Matrix Extracellular Phosphoglycoprotein), while the related m

Readability of Online Information on Core Decompression of the Hip for Avascular Necrosis.

Introduction Avascular necrosis (AVN) of the femoral head is a type of osteonecrosis, which is caused by the disruption of blood flow to the proximal femur, resulting in osteocyte death. Regression of the disease is rare, and most patients will ultimately progress to having a total hip arthroplasty performed. Early diagnosis of AVN allows treatment options beyond total hip arthroplasty. One such procedure described is core decompression of the femoral head. Health literacy is defined as the ability to make health decisions in the context of everyday life. It has been shown that lower levels of

Changes in bone biomarkers in response to different dosing regimens of cholecalciferol supplementation in children with chronic kidney disease.

BACKGROUND: The effect of different dosing regimens of cholecalciferol supplementation on bone biomarkers has not been studied in children with chronic kidney disease (CKD). METHODS: This is a post hoc analysis of a multi-center randomized controlled trial which included children with CKD stages 2-4 with vitamin D deficiency (25-hydroxy vitamin D (25OHD) < 30 ng/ml) randomized 1:1:1 to receive an equivalent dose of oral cholecalciferol as daily, weekly or monthly treatment. Markers of bone formation (bone alkaline phosphatase (BAP), procollagen I N terminal peptide (PINP)), bone resorption (t

Tracking of Stem Cells from Human Exfoliated Deciduous Teeth Labeled with Molday ION Rhodamine-B during Periodontal Bone Regeneration in Rats.

BACKGROUND AND OBJECTIVES: Chronic periodontitis can lead to alveolar bone resorption and eventually tooth loss. Stem cells from exfoliated deciduous teeth (SHED) are appropriate bone regeneration seed cells. To track the survival, migration, and differentiation of the transplanted SHED, we used super paramagnetic iron oxide particles (SPIO) Molday ION Rhodamine-B (MIRB) to label and monitor the transplanted cells while repairing periodontal bone defects. METHODS AND RESULTS: We determined an appropriate dose of MIRB for labeling SHED by examining the growth and osteogenic differentiation of

Comparative analysis of mouse bone marrow and adipose tissue mesenchymal stem cells for critical limb ischemia cell therapy.

INTRODUCTION: Critical limb ischemia (CLI) is the most advanced form of peripheral arterial disease (PAD) characterized by ischemic rest pain and non-healing ulcers. Currently, the standard therapy for CLI is the surgical reconstruction and endovascular therapy or limb amputation for patients with no treatment options. Neovasculogenesis induced by mesenchymal stem cells (MSCs) therapy is a promising approach to improve CLI. Owing to their angiogenic and immunomodulatory potential, MSCs are perfect candidates for the treatment of CLI. The purpose of this study was to determine and compare the i

Intraoperative Stromal Vascular Fraction Therapy Improves Histomorphometric and Vascular Outcomes in Irradiated Mandibular Fracture Repair.

BACKGROUND: Cell-based treatments have demonstrated the capacity to enhance reconstructive outcomes in recent decades but are hindered in clinical utility by regulatory hurdles surrounding cell culture. This investigation examines the ability of a noncultured stromal vascular fraction derived from lipoaspirate to enhance bone healing during fracture repair to further the development of translatable cell therapies that may improve outcomes in irradiated reconstruction. METHODS: Isogenic male Lewis rats were divided into three groups: fracture, irradiated fracture, and irradiated fracture with

Genotypic Analyses of the Sclerostin rs851056 and Dickkopf rs1569198 Polymorphisms in Mexican-Mestizo Postmenopausal Osteoporosis: A Case-Control Study.

Background: The Wnt/β catenin pathway promotes bone mineralization stimulating proliferation, differentiation, and survival of osteoblasts; it also inhibits osteoclast differentiation and osteocyte activity. Sclerostin (SOST) and Dickkopf 1 (DKK1) are Wnt/β catenin pathway inhibitors. Genetic variability in the expression of SOST and DKK1 might be involved in the development of postmenopausal osteoporosis (OP). Aim: To determine whether the SOST rs851056 and DKK1 rs1569198 polymorphisms are associated with OP in Mexican-Mestizo postmenopausal women. Materials and Methods: Two hundred and eight

[Comparison of scaphoid reconstruction with a non-vascularised bone graft, with and without shock waves; preliminary results].

BACKGROUND: Focused, high energy shock wave therapy (ESWT) stimulates bone healing by neo-angiogenesis and activating osteocytes. This study investigates if applying an ESWT intraoperatively improves and accelerates the healing of a scaphoid nonunion after reconstruction using a non-vascularized bone graft. PATIENTS AND METHODS: In this prospective, ongoing study, patients with a scaphoid reconstruction using a non-vascularized bone graft and stabilization for non-union, are randomized for having additionally an intraoperative ESWT (intervention group) or not (control group). In 6 weeks-inter…

A novel RGB-trichrome staining method for routine histological analysis of musculoskeletal tissues.

Morphometry and histology are essential approaches for investigation and diagnosis of musculo-skeletal disorders. Despite the advent of revolutionary methods of image analysis and high resolution three-dimensional imaging technology, basic conventional light microscopy still provides an incisive overview of the structure and tissue dynamics of the musculoskeletal system. This is crucial to both preclinical and clinical research, since several clinically relevant processes, such as bone repair, osteoarthritis, and metabolic bone diseases, display distinct, if not pathognomonic, histological fea

The Impact of Mild Autonomous Cortisol Secretion on Bone Turnover Markers.

CONTEXT: Several studies have reported increased risk of fragility fractures in patients with mild autonomous cortisol secretion (MACS), discordant to the degree of bone density deterioration. OBJECTIVE: To evaluate the effect of MACS on bone metabolism in patients with adrenal adenomas. DESIGN: Cross-sectional study with prospective enrollment, 2014-2019. SETTING: Referral center. PATIENTS: 213 patients with adrenal adenomas: 22 Cushing syndrome (CS), 92 MACS and 99 nonfunctioning adrenal tumors (NFAT). MAIN OUTCOME MEASURES: Osteocalcin, procollagen I intact N-terminal (PINP), C-termina