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Phlorizin attenuates chronic kidney disease induced bone loss by mitigating sclerostin mediated inhibition of Wnt/β-catenin signaling and ameliorating metabolic alterations.

CKD-MBD is a metabolic disorder characterized by disrupted mineral metabolism, leading to vascular calcification, renal osteodystrophy, and … localization and activating Wnt/β-catenin signaling. Phlorizin also reduced sclerostin secretion in osteocytes and reversed its inhibitory effects on primary osteoblastic cells, confirming a sclerostin-dependent mechanism. In vivo, phlorizin improved fracture healing and attenuated bone loss in 5/6th nephrectomised rats. It also improved renal function, corr …

Pinoresinol diglucoside alleviates hindlimb unloading-induced bone loss in mice.

Microgravity-induced bone loss has long been a critical issue in space exploration. While countermeasures have been suggested, none have achieved the desired effects. Pinoresinol diglucoside (PDG), an effective constituent of the medicinal herb Eucommia ulmoidis Oliv, was reported to increase peak bone mass in growing rats and mitigate dexamethasone-induced osteoporosis. However, it is unknown if it affects microgravity-induced bone loss. Here, PDG effects were investigated in cultured rat calvarial osteoblasts exposed to simulated microgravity (SMG) and in hindlimb-unloaded mice. PDG (1 × 106

Spatio-temporal characterization of compositional and cellular properties in the murine fracture callus.

Advances in the understanding of the physiological process of bone healing and its impairment (i.e., nonunion) require appropriate models an … d the healing bone allowed us to provide evidence for the transient involvement of mechanosensitive osteocytes as well as the mobilization of calcium from the unfractured bone. Our data also provide scientists with useful multidimensional reference values when interpreting data on fracture healing in mice.

FTO-engineered extracellular vesicles from bone marrow mesenchymal stem cells ameliorate Staphylococcus aureus-induced osteomyelitis via m6A-dependent suppression of autophagy and pyroptosis.

BACKGROUND: Bone marrow mesenchymal stem cells (BM-MSCs) ameliorate various orthopedic diseases through the secretion of extracellular vesicles (EVs). This study investigates the effects of FTO-overexpressing BM-MSCs-derived EVs (FTO-EVs) on osteocyte autophagy and pyroptosis in Staphylococcus aureus-associated osteomyelitis (OM). METHODS: The expression levels of N6-methyladenosine regulators were investigated in bone tissues and serum EVs obtained from patients with OM. Osteoblast MC3T3-E1 and osteocyte MLO-Y4 cells were induced with Staphylococcal Protein A (SpA) to simulate in vitro OM mod

RANKL-derived peptide MHP1-AcN attenuates ovariectomy-induced osteoporosis by targeting RANK and TNFR1 in mice.

PURPOSE: Estrogen deficiency following menopause increases receptor activator of nuclear factor-kappa B ligand (RANKL) expression in osteoblasts, thereby promoting osteoclast differentiation, and enhances T cell-derived tumor necrosis factor-alpha (TNFα) production, which induces sclerostin expression in osteocytes, thereby inhibiting bone formation. This study aimed to develop a novel uncoupling therapeutic agent for osteoporosis. METHODS: We developed microglial healing peptide 1 with N-terminal acetylation and C-terminal amidation (MHP1-AcN), a modified RANKL peptide with N-terminal acetyl…

Pilot study of a novel resection extent determination method using bone single-photon emission CT-standardized uptake value in medication-related osteonecrosis of the jaw.

OBJECTIVE: Surgery is the standard treatment for medication-related osteonecrosis of the jaw (MRONJ). However, there are few reports on the … led significant osteocyte necrosis in cold regions, whereas areas with an SUV of 9 displayed normal osteocytes, newly formed bone, and mild inflammatory cell infiltration. CONCLUSION: This study suggests that the setting of the SPECT cold region using bone SPECT-SUV may allow for the estimation of the extent of resection in early-to-intermediate-stage MRONJ …

Research progress of connexin 43 mediated gap junction communication regulating bone metabolism in glucocorticoid-induced osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) is a refractory orthopedic disease that commonly affects young and middle-aged individuals. Long-term and high-dose use of glucocorticoids (GCs) is one of the main causes. Currently, the pathological mechanism of GCs-induced ONFH remains unclear, which poses difficulties for clinical prevention and treatment. This article focuses on reviewing the roles of gap junctions (GJs) and connexin 43 (Cx43) in GCs-induced ONFH. Under normal circumstances, cells in bone tissue form a network structure through GJs to maintain bone metabolic balance. However, GCs ca

Regulation of Skeletal Development and Maintenance by Runx2 and Sp7.

Runx2 (runt related transcription factor 2) and Sp7 (Sp7 transcription factor 7) are crucial transcription factors for bone development. The … ession and regulates osteoblast/osteocyte process formation, which is necessary for the survival of osteocytes and the prevention of cortical porosity. SP7 mutations cause osteogenesis imperfecta in rare cases. Runx2 is an important pathogenic factor, while Runx1, Runx3, and Cbfb are protective factors in osteoarthritis development.

Normal Bone Matrix Mineralization but Altered Growth Plate Morphology in the LmnaG609G/G609G Mouse Model of Progeria.

Hutchison-Gilford progeria syndrome (HGPS) is a rare genetic disease caused by a mutation in LMNA, the gene encoding A-type lamins, leading to premature aging with severely reduced life span. HGPS is characterized by growth deficiency, subcutaneous fat and muscle issues, wrinkled skin, alopecia, and atherosclerosis. Patients also develop a bone phenotype with reduced bone mineral density, osteolysis and striking demineralization of long bones. To further clarify the tissue modifications in HGPS, we characterized bone mineralization in the LmnaG609G/G609G progeria mouse model. Femurs from 8-wee

Mitigation of BMP-induced Inflammation in Craniofacial Bone Regeneration and Improvement of Bone Parameters by Dietary Hesperidin.

Based on anti-inflammatory and osteogenic properties of hesperidin (HE), we hypothesized its systemic administration could be a cost-effective method of improving BMP-induced bone regeneration. Sprague-Dawley rats were allocated into 4 groups (n=10/group): a 5-mm critical-sized mandible defect + collagen scaffold or, scaffold + 1 μg of BMP2 with and without dietary HE at 100 mg/kg. HE was administered by oral gavage 4 weeks prior to surgeries until euthanasia at day 7 or 14. The healing tissue within the defect collected at day 7 was subjected to gene expression analysis. Mandibles harvested a

Micro-scale vertebral features in postmenopausal women with alcohol-associated and metabolic-associated fatty liver disease: ex vivo bone quality analyses.

PURPOSE: Although epidemiological studies indicate increased fracture risk in women with alcohol-associated liver disease (AALD) and metabolic-associated fatty liver disease (MAFLD), data about their micro-scale bone features are still limited. We aimed to characterize bone quality changes in the anterior mid-transverse part of the first lumbar vertebral body collected from 32 adult postmenopausal females. Based on pathohistological assessment of the liver tissue, individuals were divided into AALD (n = 13), MAFLD (n = 9), and control group (n = 10). METHODS: We analyzed trabecular and cortic

Astragalus polysaccharide ameliorates steroid-induced osteonecrosis of the femoral head by regulating miR-200b-3p-mediated Wnt/β-catenin signaling pathway via inhibiting SP1 expression : Astragalus polysaccharide regulates SONFH via SP1.

BACKGROUND: Steroid-induced osteonecrosis of the femoral head (SONFH) is the necrosis of the femur bone caused by prolonged and massive use of corticosteroids. The present study probed into the significance of Astragalus polysaccharide (APS) in SONFH progression. METHODS: SONFH cell model was constructed using murine long bone osteocyte Y4 (MLO-Y4) cells and then treated with APS. mRNA microarray analysis selected differentially expressed genes between control group and SONFH group. RT-qPCR determined SP1 and miR-200b-3p expression. Levels of SP1, β-catenin, autophagy-related proteins (LC3II/

Mineral tessellation in mouse enthesis fibrocartilage, Achilles tendon, and Hyp calcifying enthesopathy: A shared 3D mineralization pattern.

The hallmark of enthesis architecture is the 3D compositional and structural gradient encompassing four tissue zones - tendon/ligament, uncalcified fibrocartilage, calcified fibrocartilage and bone. This functional gradient accommodates the large stiffness differential between calcified bone and uncalcified tendon/ligament. Here we analyze in 3D the organization of the mouse Achilles enthesis and mineralizing Achilles tendon in comparison to lamellar bone. We use correlative, multiscale high-resolution volume imaging methods including μCT with submicrometer resolution and FIB-SEM tomography (b

Elevated levels of active Transforming Growth Factor β1 in the subchondral bone relate spatially to cartilage loss and impaired bone quality in human knee osteoarthritis.

OBJECTIVE: The association between the spatially distributed level of active TGFβ1 in human subchondral bone, and the characteristic structural and cellular parameters of human knee OA, was assessed. DESIGN: Paired subchondral bone samples from 35 OA arthroplasty patients, (15 men and 20 women, aged 69 ± 9 years) were obtained from beneath macroscopically present (CA+) or denuded cartilage (CA-) to determine the concentration of active TGFβ1 (ELISA) and its relationship to bone quality (synchrotron micro-CT), cellularity, and vascularization (histology). RESULTS: Bone samples beneath (CA-) r

Intra-articular kinetics of a cartilage targeting cationic PEGylated protein for applications in drug delivery.

OBJECTIVES: Cartilage targeting cationic glycoprotein Avidin was PEGylated to synthesize a multi-arm Avidin (mAv) nano-construct with high d … CONCLUSIONS: mAv's ability to target a variety of joint tissues, chondrocytes, and peri-articular osteocytes without sequestration in synovial fluid makes it a versatile carrier for delivering a wide range of drugs for treating a broad class of musculoskeletal diseases. Drugs can be conjugated using simple aqueous based avidin-biotin reaction, supporting i …

Effect of pentoxifylline and α-tocopherol on medication-related osteonecrosis of the jaw in rats: Before and after dental extraction.

OBJECTIVE: Evaluate the effect of pentoxifylline and α-tocopherol administration in the prevention or treatment of medication-related jaw os … gaps and the necrotic area, decrease the presence of bone sequestration and increase the number of osteocytes and alveolar blood flow (p < 0.05). However, BP/PT-prev group showed only a reduction in the necrotic area percentage when compared to BP-prev (p < 0.05). CONCLUSIONS: Pentoxifylline and α-tocopherol administration before tooth extraction was not e …

Pulsed Electromagnetic Fields Ameliorate Skeletal Deterioration in Bone Mass, Microarchitecture, and Strength by Enhancing Canonical Wnt Signaling-Mediated Bone Formation in Rats with Spinal Cord Injury.

Spinal cord injury (SCI) leads to extensive bone loss and high incidence of low-energy fractures. Pulsed electromagnetic fields (PEMF) treatment, as a non-invasive biophysical technique, has proven to be efficient in promoting osteogenesis. The potential osteoprotective effect and mechanism of PEMF on SCI-related bone deterioration, however, remain unknown. The spinal cord of rats was transected at vertebral level T12 to induce SCI. Thirty rats were assigned to the control, SCI, and SCI+PEMF groups (n = 10). One week after surgery, the SCI+PEMF rats were subjected to PEMF (2.0 mT, 15 Hz, 2 h/d

An Early Myeloma Bone Disease Model in Skeletally Mature Mice as a Platform for Biomaterial Characterization of the Extracellular Matrix.

Multiple myeloma (MM) bone disease is characterized by osteolytic bone tissue destruction resulting in bone pain, fractures, vertebral collapse, and spinal cord compression in patients. Upon initial diagnosis of MM, almost 80% of patients suffer from bone disease. Earlier diagnosis and intervention in MM bone disease would potentially improve treatment outcome and patient survival. New preclinical models are needed for developing novel diagnostic markers of bone structural changes as early as possible in the disease course. Here, we report a proof-of-concept, syngeneic, intrafemoral MOPC315.BM

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… High-magnification images of the osteocyte morphology in the MM-injected femur ( Figure 6(f) ) showed larger, irregular-shaped osteocyte lacunae within a disorganized canaliculi network architecture ( Figure 7(a) ) next to flat osteocyte lacunae organized in a lamellar structure ( Figure 7(b) ). … Osteocytes communicate with other osteocytes and with cells on the bone periosteal or endosteal surface, such as lining cells, stromal cells, osteoblasts, and/or osteoclasts, through an intricate canaliculi network [ 20 , 21 ]. …

A comparison of alendronate to varying magnitude PEMF in mitigating bone loss and altering bone remodeling in skeletally mature osteoporotic rats.

Pulsed electromagnetic field (PEMF) treatments stimulate bone formation activities though further work is needed to optimize its therapeutic benefit. PEMF can generate local potential gradients and electric currents that have been suggested to mimic bone electrochemical responses to load. In line with this reasoning, a recent publication reported that PEMF application on isolated bone tissue induced detectable micro-vibrations (doi:https://doi.org/10.1109/TMAG.2016.2515069). To determine the ability of PEMF to intervene in a rat model of osteoporosis, we tested its effect on trabecular and cor

Multi-Scale Approach for the Evaluation of Bone Mineralization in Strontium Ranelate-Treated Diabetic Rats.

Long-term diabetes mellitus can induce osteopenia and osteoporosis, an increase in the incidence of low-stress fractures, and/or delayed fracture healing. Strontium ranelate (SrR) is a dual-action anti-osteoporotic agent whose use in individuals with diabetic osteopathy has not been adequately evaluated. In this study, we studied the effects of an oral treatment with SrR and/or experimental diabetes on bone composition and biomechanics. Young male Wistar rats (half non-diabetic, half with streptozotocin/nicotinamide-induced diabetes) were either untreated or orally administered 625 mg/kg/day o