scholarly journals Triptolide Prevents Bone Destruction in the Collagen-Induced Arthritis Model of Rheumatoid Arthritis by Targeting RANKL/RANK/OPG Signal Pathway

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Chunfang Liu ◽  
Yanqiong Zhang ◽  
Xiangying Kong ◽  
Liuluan Zhu ◽  
Jian Pang ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Mononuclear Cells ◽  
Volume Fraction ◽  
Bone Destruction ◽  
Signal Pathway ◽  
Therapeutic Effects ◽  
Mineral Density ◽  
Collagen Induced Arthritis ◽  
Bone Volume Fraction ◽  
Trabecular Thickness

Focal bone destruction within inflamed joints is the most specific hallmark of rheumatoid arthritis (RA). Our previous study indicated that the therapeutic efficiency of triptolide in RA may be due partially to its chondroprotective and anti-inflammatory effects. However, its roles in bone destruction are still unclear. In this study, our data firstly showed the therapeutic effects of triptolide on severity of arthritis and arthritis progression in collagen-induced arthritis (CIA) mice. Then, by micro-CT quantification, triptolide treatment significantly increased bone mineral density, bone volume fraction, and trabecular thickness and decreased trabecular separation of inflamed joints. Interestingly, triptolide treatment could prevent the bone destruction by reducing the number of osteoclasts in inflamed joints, reducing the expression of receptor activator of NF-κB (RANK) ligand (RANKL) and RANK, increasing the expression of osteoprotegerin (OPG), at both mRNA and protein levels, and decreasing the ratio of RANKL to OPG in sera and inflamed joints of CIA mice, which were further confirmed in the coculture system of human fibroblast-like synovial and peripheral blood mononuclear cells. These findings offer the convincing evidence for the first time that triptolide may attenuate RA partially by preventing the bone destruction and inhibit osteoclast formation by regulating RANKL/RANK/OPG signal pathway.

scholarly journals Antiosteoporosis Effect ofRadix ScutellariaeExtract on Density and Microstructure of Long Bones in Tail-Suspended Sprague-Dawley Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Chen-Rui Li ◽  
Guang-Wei Zhang ◽  
Yin-Bo Niu ◽  
Ya-Lei Pan ◽  
Yuan-Kun Zhai ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Volume Fraction ◽  
Bone Microarchitecture ◽  
Osteoclast Differentiation ◽  
Hindlimb Unloading ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Trabecular Thickness ◽  
Radix Scutellariae

Radix Scutellariae (RS), a medicinal herb, is extensively employed in traditional Chinese medicines and modern herbal prescriptions. Two major flavonoids in RS were known to induce osteoblastic differentiation and inhibit osteoclast differentiation, respectively. This study aimed to investigate the effect ofRadix Scutellariaeextract (RSE) against bone loss induced by mechanical inactivity or weightlessness. A hindlimb unloading tail-suspended rat model (TS) was established to determine the effect of RSE on bone mineral density and bone microarchitecture. Treatment of RSE at 50 mg/kg/day and alendronate (ALE) at 2 mg/kg/day as positive control for 42 days significantly increased the bone mineral density and mechanical strength compared with TS group. Enhanced bone turnover markers by TS treatment were attenuated by RSE and ALE administration. Deterioration of bone trabecula induced by TS was prevented. Moreover, both treatments counteracted the reduction of bone volume fraction, trabecular thickness and number, and connectivity density. In conclusion, RSE was demonstrated for the first time to prevent osteoporosis induced by TS treatment, which suggests the potential application of RSE in the treatment of disuse-induced osteoporosis.

scholarly journals The Incorporation of Platelet-rich Plasma into Calcium Phosphate Cement Enhances Bone Regeneration in Osteoporosis

2014 ◽  
Vol 6;17 (6;12) ◽  
pp. E737-E745
Author(s):  
Kyung-Hoon Kim
Keyword(s):  
Bone Regeneration ◽  
Trabecular Bone ◽  
Volume Fraction ◽  
Platelet Rich Plasma ◽  
Bone Volume ◽  
Filler Materials ◽  
Trabecular Bone Volume ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Trabecular Thickness

Background: Polymethyl methacrylate (PMMA) bone cement is widely used for osteoplasty. However, previous studies have demonstrated the adverse effects of PMMA due to its excessive stiffness and heat production. Recently, calcium phosphate cement (CPC) that overcomes those negative effects has been successfully applied in osteoplasty. The potential problem of CPC is markedly less initial stiffness. It leads to progressive, repeated collapse in the treated vertebra before CPC has been replaced by new bone that would provide substantial improvement in compressive strength and stiffness. The activated platelets in platelet-rich plasma (PRP) release a high concentration of growth factors which play an important role in bone healing. Objective: To investigate whether PRP could accelerate the osteoconduction of CPC and enhance the bone strength of the treated vertebra in an animal model. Study Design: Controlled animal study. Setting: Laboratory animal study, Methods: Thirty-two female Sprague-Dawley rats were ovariectomized at 8 weeks of age. After 3 months, they were randomly divided into 4 groups and received cement augmentation in the fifth caudal spine with different filler materials; sham-operated rats (S), PMMA (P), CPC (C), and CPC + PRP (CP). Bone mineral density (BMD) and trabecular type-associated morphological parameters, including trabecular bone volume fraction and trabecular thickness in the augmented caudal spine, were evaluated by micro-computed tomography (mirco-CT) 2 weeks after the cementoplasty. Histological analysis was also performed to compare the bone regeneration. Results: The trabecular bone volume fraction in the CP group was significantly greater than those of all the other groups. Trabecular thickness was higher in the CP group than the S and P groups. This augmented trabecular structure in the CP group accordingly showed higher BMD. Histological evaluations showed significantly more bone regeneration in the CP group. Limitations: There has been a concern that the effect of PRP would be dependent on the species, and might show different results in humans. Baseline values of micro-CT analysis were not measured, which could have provided exact evidence of the changes in trabecular microarchitecture parameters and cement resorption profiles. Finally, caudal vertebrae with filler materials used in biological study should have been compared by their mechanical properties using biomechanical evaluations for a more coherent study, which was not possible due to technical problems. Conclusions: Incorporating PRP into CPC could accelerate osteoconduction in the augmented vertebra leading to improvement of trabecular bone microarchitecture and BMD in rats. Key words: Bone mineral density, calcium phosphates, cementoplasty, histology, osteoconduction, osteoporosis, platelet-rich plasma, polymethyl methacrylate, vertebra

scholarly journals Comparison of Trabecular Bone Mineral Density Measurement Using Hounsfield Unit and Trabecular Microstructure in Orthodontic Patients Using Cone-Beam Computed Tomography

2021 ◽  
Vol 11 (3) ◽  
pp. 1028
Author(s):  
Tae-Hyun Kim ◽  
Dong-Yul Lee ◽  
Seok-Ki Jung
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Volume Fraction ◽  
Cervical Vertebra ◽  
Hounsfield Unit ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Trabecular Thickness ◽  
Trabecular Microstructure ◽  
Trabecular Number

The aim of this study was to measure the bone mineral density of specific regions of maxilla, mandible, and first cervical vertebra using the Hounsfield unit and trabecular microstructure pattern analysis and to compare the two methods. In this study, cone-beam computed tomography (CBCT) images were obtained from 58 patients. Trabecular thickness, trabecular number, trabecular separation, and bone volume fraction were measured in 484 regions for trabecular microstructure parameters and Hounsfield unit was measured for the grayscale value. There was no difference in bone mineral density between the right and left side in every site and between males and females. Trabecular thickness and trabecular number were high in the order of anterior base of the maxilla, mandibular body, first cervical vertebra, and mandibular condyle. Bone volume fraction and Hounsfield unit were high in the order of anterior base of the maxilla, mandibular body, mandibular condyle, and first cervical vertebra (p < 0.05). Trabecular thickness, trabecular number, and bone volume fraction was positively correlated to the Hounsfield unit, and trabecular separation was negatively correlated to the Hounsfield unit (p < 0.005). This study suggests that it is possible to compare the bone mineral density of trabecular bone in various sites using the Hounsfield unit and trabecular microstructure pattern analysis.

MicroRNA-29b Promotes Subchondral Bone Loss in TMJ Osteoarthritis

2020 ◽  
Vol 99 (13) ◽  
pp. 1469-1477
Author(s):  
J.L. Sun ◽  
J.F. Yan ◽  
S.B. Yu ◽  
J. Zhao ◽  
Q.Q. Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Bone Loss ◽  
Bone Remodeling ◽  
Subchondral Bone ◽  
Volume Fraction ◽  
Cartilage Degradation ◽  
Specific Inhibition ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Trabecular Thickness

Abnormal subchondral bone remodeling plays important roles during osteoarthritis (OA) pathology. Recent studies show that bone marrow mesenchymal stem cells (BMSCs) in osteoarthritic subchondral bones exhibit a prominent pro-osteoclastic effect that contributes to abnormal subchondral bone remodeling; however, the pathologic mechanism remains unclear. In the present study, we used a mouse model with OA-like change in the temporomandibular joint (TMJ) induced by an experimentally unilateral anterior crossbite (UAC) and found that the level of microRNA-29b ( miR-29b), but not miR-29a or miR-29c, was markedly lower in BMSCs from subchondral bones of UAC mice as compared with that from the sham control mice. With an intra-articular aptamer delivery system, BMSC-specific overexpression of miR-29b by aptamer-agomiR-29b rescued subchondral bone loss and osteoclast hyperfunction in UAC mice, as demonstrated by a significant increase in bone mineral density, bone volume fraction, trabecular thickness, and the gene expression of osteocalcin and Runx2 but decreased trabecular separation, osteoclast number and osteoclast surface/bone surface, and the gene expression of cathepsin K, Trap, Wnt5a, Rankl, and Rank as compared with those in the UAC mice treated by aptamer-NC (all P < 0.05). In addition, BMSC-specific inhibition of miR-29b by aptamer-antagomiR-29b exacerbated those responses in UAC mice. Notably, although it primarily affected miR-29b levels in the subchondral bone (but not in cartilage and synovium), BMSC-specific overexpression of miR-29b in UAC mice largely rescued OA-like cartilage degradation, including decreased chondrocyte density, cartilage thickness, and the percentage areas of proteoglycans and type II collagen, while BMSC-specific inhibition of miR-29b aggravated these characteristics of cartilage degradation in UAC mice. Moreover, we identified Wnt5a, but not Rankl or Sdf-1, as the direct target of miR-29b. The results of the present study indicate that miR-29b is a key regulator of the pro-osteoclastic effects of BMSCs in TMJ-OA subchondral bones and plays important roles in the TMJ-OA progression.

scholarly journals Pax5 Negatively Regulates Osteoclastogenesis through Downregulation of Blimp1

2021 ◽  
Vol 22 (4) ◽  
pp. 2097
Author(s):  
Jiyeon Yu ◽  
Sumi Kim ◽  
Nari Lee ◽  
Hyoeun Jeon ◽  
Jun Lee ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Volume Fraction ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mineral Density ◽  
Lineage Specification ◽  
Bone Volume Fraction ◽  
Trabecular Thickness ◽  
Negative Role

Paired box protein 5 (Pax5) is a crucial transcription factor responsible for B-cell lineage specification and commitment. In this study, we identified a negative role of Pax5 in osteoclastogenesis. The expression of Pax5 was time-dependently downregulated by receptor activator of nuclear factor kappa B (RANK) ligand (RANKL) stimulation in osteoclastogenesis. Osteoclast (OC) differentiation and bone resorption were inhibited (68.9% and 48% reductions, respectively) by forced expression of Pax5 in OC lineage cells. Pax5 led to the induction of antiosteoclastogenic factors through downregulation of B lymphocyte-induced maturation protein 1 (Blimp1). To examine the negative role of Pax5 in vivo, we generated Pax5 transgenic (Pax5Tg) mice expressing the human Pax5 transgene under the control of the tartrate-resistant acid phosphatase (TRAP) promoter, which is expressed mainly in OC lineage cells. OC differentiation and bone resorption were inhibited (54.2–76.9% and 24.0–26.2% reductions, respectively) in Pax5Tg mice, thereby contributing to the osteopetrotic-like bone phenotype characterized by increased bone mineral density (13.0–13.6% higher), trabecular bone volume fraction (32.5–38.1% higher), trabecular thickness (8.4–9.0% higher), and trabecular number (25.5–26.7% higher) and decreased trabecular spacing (9.3–10.4% lower) compared to wild-type control mice. Furthermore, the number of OCs was decreased (48.8–65.3% reduction) in Pax5Tg mice. These findings indicate that Pax5 plays a negative role in OC lineage specification and commitment through Blimp1 downregulation. Thus, our data suggest that the Pax5–Blimp1 axis is crucial for the regulation of RANKL-induced osteoclastogenesis.

scholarly journals Bone microarchitectural parameters can detect oxytocin induced changes prior to bone density on mitigating bone deterioration in rabbit osteoporosis model using micro-CT

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuyou Qiu ◽  
Cuisong Tang ◽  
Mario Serrano-Sosa ◽  
Jian Hu ◽  
Jingqi Zhu ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Mineral ◽  
Volume Fraction ◽  
Rabbit Model ◽  
Vehicle Group ◽  
Control Group ◽  
Micro Ct ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Trabecular Thickness

Abstract Background This study is aimed to determine the efficacy of X-Ray Microtomography (micro-CT) in predicting oxytocin (OT) treatment response in rabbit osteoporosis(OP) model. Methods Sixty-five rabbits were randomly divided into three groups: control group, ovariectomy (OVX) -vehicle and OVX-oxytocin group. The controls underwent sham surgery. OVX-vehicle and OVX-oxytocin groups were subjected to bilateral OVX. The rabbits in OVX-oxytocin group were injected with oxytocin. In the 0th, 4th, 8th, 10th and 12th weeks post OVX operation, bone mineral density (BMD) and bone micro-architectural parameters were measured in three groups. Results Bone mineral density (BMD), bone volume fraction (BV/TV), Trabecular Number (Tb.N), and Trabecular Thickness (Tb.Th) decreased, while Trabecular Spacing (Tb.Sp) and Structure Model Index (SMI) increased overtime in all the three groups. In OVX-oxytocin group, the bone deterioration tendency is slowing down compared with that of the OVX-vehicle group. The BMD of the OVX-oxytocin group was significantly lower than those in the OVX-vehicle group at 12th week (P = 0.017). BV/TV and Tb.Sp in OVX-oxytocin group changed significantly from 8th week (P = 0.043) and 12th week (P = 0.014), which is earlier than that of BMD and other bone micro-architectural parameters. Conclusion BV/TV and Tb.Sp changed prior to BMD and other bone micro-architectural parameters with oxytocin intervention, which indicate that they are more sensitive markers for predicting early osteoporosis and treatment monitoring when using micro-CT to evaluate osteoporosis rabbit model.

scholarly journals The Balance between Orthodontic Force and Radiation in the Jawbone: Microstructural, Histological, and Molecular Study in a Rat Model

Biology ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1203
Author(s):  
Hadas Dorchin-Ashkenazi ◽  
Ravit Ginat-Koton ◽  
Yankel Gabet ◽  
Yehuda Klein ◽  
Stella Chaushu ◽  
...  
Keyword(s):  
Rat Model ◽  
Tooth Movement ◽  
Volume Fraction ◽  
Molecular Study ◽  
External Beam Radiation ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Beam Radiation ◽  
Trabecular Thickness ◽  
Orthodontic Force

Irradiation of facial bones is associated with a lifelong risk of osteonecrosis. In a rat model, maxillae were exposed to a single 5 Gy dose of external beam radiation and orthodontic force was applied for 2 weeks on the first maxillary molar; control rats were treated identically without radiation. Tooth movement in irradiated jaws was 30% less than in controls, representing radiation-related damage. Micro-CT, histological, and molecular outcomes of orthodontic tooth movement were studied. Microstructurally, bone parameters (trabecular thickness, bone volume fraction, bone mineral density) were significantly affected by orthodontic force but not by radiation. Histological parameters were influenced only by orthodontic force, especially by an increase in osteoclasts. A molecular study revealed a differential distribution of cells expressing pre-osteoclast markers (RANK+—majority, CD11b+, CD14+—minority), with changes being influenced by orthodontic force (increased CD11b+ and CD14+ cells) and also by radiation (decreased RANK+ cells). The activation status of osteoclasts (TRAP staining) showed an orthodontic-force-related increase, which probably could not fully compensate for the radiation-associated impairment. The overall balance showed that orthodontic force had elicited a substantial microstructural, histological, and functional normalization process in irradiated maxillae but a radiation-induced impact was still conspicuous. Additional studies are needed to validate these findings.

scholarly journals Autologous Adipose-Derived Stem Cells, Platelet-Rich Plasma, and Fibrin Enhance Healing of Mandibular Bone Defects in Swine

2020 ◽  
pp. 1-9
Author(s):  
Matthew B. Wheeler ◽  
Aaron J. Maki ◽  
Anna C. Ercolin ◽  
Jamey J. Cooper ◽  
Kelly S. Roballo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Volume Fraction ◽  
Critical Size ◽  
Platelet Rich Plasma ◽  
Therapeutic Effects ◽  
Mineral Density ◽  
Bone Volume Fraction ◽  
Critical Size Defects ◽  
Autologous Platelet Rich Plasma ◽  
Autologous Platelet

The primary aim of this study was to assess the therapeutic effects of autologous platelet-rich plasma and fibrin scaffolds combined with autologous adipose stem cells (ASCs) for critical-size defects in the pig mandible. Fibrin scaffolds supplemented with calcium hydrogen phosphate and platelet-derived growth factors were hypothesized to accelerate healing in porcine mandible bone compared to ASC-only injections and untreated controls. Three treatments included the use of autologous ASCs from liposuction with the addition of platelet-rich plasma, fibrin scaffolds, or as cell-only controls. All three treatments using ASCs were determined to increase bone mineral density and bone volume fraction compared to untreated controls. In general, the addition of both platelet-rich plasma and fibrin scaffolds to autologous ASCs from liposuction improved bone healing of critical-size defects.

scholarly journals SAT0007 BLOCKING HISTAMINE-RELEASING FACTOR/TRANSLATIONALLY CONTROLLED TUMOR PROTEIN (HRF/TCTP) ATTENUATES AGGRESSIVENESS OF FIBROBLAST-LIKE SYNOVIOCYTES AND AMELIORATES COLLAGEN-INDUCED ARTHRITIS IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 934.3-934
Author(s):  
M. Kim ◽  
Y. Choe ◽  
H. Lee ◽  
Y. H. Cheon ◽  
S. I. Lee
Keyword(s):  
Rheumatoid Arthritis ◽  
Cancer Progression ◽  
Inflammatory Responses ◽  
Joint Destruction ◽  
Serum Levels ◽  
Therapeutic Effects ◽  
Collagen Induced Arthritis ◽  
Translationally Controlled Tumor Protein ◽  
Biochemical Analyses ◽  
Fibroblast Like Synoviocytes

Background:Histamine-releasing factor/translationally controlled tumor protein (HRF/TCTP) stimulates cancer progression and allergic responses. Increased expression of HRF/TCTP occurs in joints of rheumatoid arthritis (RA) patients, but the role of HRF/TCTP in RA remains undefinedObjectives:In this study, we explored the pathogenic significance of HRF/TCTP and evaluated therapeutic effects of HRF/TCTP blockade in RA.Methods:HRF/TCTP transgenic (TG) and knockdown (KD) mice with collagen-induced arthritis (CIA) were used to determine experimental phenotypes of RA. HRF/TCTP levels were measured in sera and joint fluids in patients with RA and compared to those with osteoarthritis, ankylosing spondylitis, Behcet disease, and healthy controls. HRF/TCTP expression was also assessed in synovium and fibroblast-like synoviocytes (FLS) obtained from RA or OA patients. Finally, we assessed effects of HRF/TCTP and dimerized HRF/TCTP binding peptide-2 (dTBP2), an inhibitor of HRF/TCTP, in RA-FLS and CIA mice.Results:Our clinical, radiological, histological, and biochemical analyses indicate that inflammatory responses and joint destruction were increased in HRF/TCTP TG mice, and decreased in KD mice compared to wild-type littermates. HRF/TCTP levels were higher in sera, synovial fluid, synovium, and FLS of patients with RA than in control groups. Serum levels of HRF/TCTP correlated well with disease activity in RA. Tumor-like aggressiveness of RA-FLS was exacerbated by HRF/TCTP stimulation and ameliorated by dTBP2 treatment. dTBP2 exerted protective and therapeutic effects in CIA mice, and had no detrimental effect in a murine tuberculosis model.Conclusion:Our results indicate that HRF/TCTP represents a novel biomarker and therapeutic target for diagnosis and treatment of RA.References:N/AAcknowledgments :National Research Foundation of KoreaKorea Health Industry Development InstituteDisclosure of Interests:None declared

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