Comparison of bone biomechanical properties after bone marrow mesenchymal stem cell or alendronate treatment in an osteoporotic animal model

2019 ◽  
Vol 64 (6) ◽  
pp. 721-727
Author(s):  
Chengdong Piao ◽  
Zhengwei Li ◽  
Jie Ding ◽  
Daliang Kong

Abstract The aim of this study was to explore the effects of bone marrow mesenchymal stem cells (BMMSCs) and alendronate sodium (ALN) intervention on osteoporosis (OP). Sixty-eight 6-month-old healthy female Sprague Dawley (SD) rats were used to generate an OP model by removal of the ovaries. After 12 weeks, rats were treated with BMMSCs (BMMSC group) or ALN (ALN group) for 5 weeks. Serum type I collagen C terminal peptide (CTX_1), procollagen type I N-terminal propeptide (PINP), and bone alkaline phosphatase (BALP) were tested along with the femur bone density and other properties, including bone mineral density (BMD), BALP, percent trabecular area (BV/TV), trabecular thickness (Tb.Th), trabecular number (TbN), maximum load, maximum stress, maximum strain, and elastic modulus. BMD, BALP, BV/TV, Tb.Th, TbN, maximum load, maximum stress, maximum strain, and elastic modulus values were higher in the BMMSC group versus the ALN group relative to the control group (p < 0.05); CTX_1, PINP, trabecular separation (Tb.Sp), and osteoclast number (OC.N) were lowest in the BMMSC group versus the ALN group relative to the control group (p < 0.05). Both BMMSCs and ALN could improve the metabolic function and bone quality in osteoporotic mice while restoring the strength and toughness of bones. The intervention effects of BMMSCs are better than ALN in this model.

2018 ◽  
Vol 36 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Jun Zhou ◽  
Peirui Zhong ◽  
Ying Liao ◽  
Jing Liu ◽  
Yuan Liao ◽  
...  

Objectives To investigate the effects of electroacupuncture (EA) on subchondral bone mass and cartilage degeneration in an experimental animal model of osteoarthritis (OA) induced by ovariectomy (OVX). Methods Ninety 3-month-old female Sprague-Dawley rats were randomly divided into the following three groups (n = 30 each): sham operation without treatment (control group); OVX without treatment (OVX group);, and ovariectomy with EA treatment (EA group). Rats in the EA group received EA treatment from the day of OVX. Ten rats in each group were randomly killed at 4, 8 and 12 weeks after operation. Results EA reduced urine C-terminal cross-linking telopeptide of type I collagen from 4 weeks after OVX, reduced C-terminal cross-linking telopeptide of type II collagen and body weight from 8 weeks after OVX, and increased serum 17β-oestradiol from 4 weeks after OVX compared with the OVX group (all p<0.01). In the EA group, trabecular bone volume ratio, trabecular thickness and trabecular number increased, and trabecular separation were reduced at each time point compared with the OVX group (p<0.05, p<0.01, respectively). In the EA group, osteoprotegerin (OPG) expression was increased and receptor activator of nuclear factor kappa-B ligand (RANKL) expression was reduced at each time point compared with the OVX group (p<0.05, p<0.01, respectively). Mankin scores and mRNA expression of matrix metalloproteinase-13 (MMP-13) were lower in EA versus OVX groups at 12 weeks after OVX (both p<0.01). Conclusion The results suggest that EA inhibits subchondral bone loss by regulating RANK/RANKL/OPG signalling and protects articular cartilage by inhibiting MMP-13 in OVX rats.


2019 ◽  
Vol 47 (11) ◽  
pp. 2729-2736
Author(s):  
Jun Lu ◽  
Connie S. Chamberlain ◽  
Ming-liang Ji ◽  
Erin E. Saether ◽  
Ellen M. Leiferman ◽  
...  

Background: Despite widespread acceptance of fresh autologous bone marrow (BM) for use in clinical practice, limited information exists to analyze if tendon-to-bone healing could be accelerated with local use of fresh autologous BM. Purpose: To investigate the effect of fresh autologous BM on tendon-to-bone healing with a novel rat model. Study Design: Controlled laboratory study. Methods: An extra-articular bone tunnel was created and filled with an autologous tendon graft in skeletally mature Sprague-Dawley rats (N = 60). They were then randomly divided into 3 groups: BM group (injection of fresh autologous BM into the tendon-bone interface, n = 20), BM-derived mesenchymal stem cell (BMSC) group (injection of allogenic cultured BMSCs, n = 20), and the control group (tendon-bone interface without injection of BM or BMSCs, n = 20). Biomechanical, histological, and immunohistochemical analyses were performed at 2 and 6 weeks after surgery. Results: The BM group showed a relatively well-organized and dense connective tissue interface with better orientation of collagen fibers as compared with the BMSC group. At 2 weeks, the tendon-bone interface tissue thickness of the BMSC group was 140 ± 25 μm (mean ± SEM), which was significantly greater than the BM group (58 ± 15 μm). The BM group showed fewer M1 macrophages at the tendon-bone interface at 2 and 6 weeks ( P < .001). In contrast, there were more M2 macrophages at the interface in the BM group 2 and 6 weeks postoperatively when compared with controls and the BMSC group ( P < .001). Biomechanical tests revealed significantly higher stiffness in the BM group versus the control and BMSC groups at 2 and 6 weeks after surgery ( P < .05). Load to failure showed similar trends to stiffness. Conclusion: These findings indicate that local delivery of fresh autologous BM enhances tendon-to-bone healing better than the alternative treatments in this study. This effect may be partially due to the observed modulation of inflammatory processes, especially in M2 macrophage polarization. Clinical Relevance: Fresh autologous BM could be a treatment option for this disorder.


Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2325-2325
Author(s):  
Mo Yang ◽  
Min Zhou ◽  
Su yi Li ◽  
Beng Chong ◽  
Xiao jing Li

Abstract Thrombocytosis and inflammation cytokines may be involved in the pathogenesis of vasculitis. Our previous study have showed that major inflammation cytokine IL-1β play an important role on in-vitro megakaryopoiesis (Yang M et al, Br J Haematol 2000). In this study, we investigated the changes of IL-1β and megakaryopoiesis and the effect of aspirin in an immune vasculitis model. Rabbit immune vasculitis model was established by intravenous injection of bovine serum albumin. In this model, platelet number and function of periphery blood, megakaryocyte number and the CFU-MK formation of the bone marrow, and serum levels of inflammatory cytokines were investigated. After treatment with BSA for 7 days, the platelet count, platelet aggregation and the expression of AnnexinⅤ were significantly increased in this vasculitis model group compared with normal control group (n=6). The serum levels of inflammatory cytokine IL-1β was also significantly higher in vasculitis model. There were positive correlations between platelet count and IL-1β levels (R=0.55), platelet aggregation and IL-1β levels (R=0.603). Treatment with aspirin (100 mg/kg/d) significantly decreased all these parameters, showing aspirin had anti-platelets and anti-inflammation effects. Our results also demonstrated that megakaryocyte number and the formation of CFU-MK were significantly increased in vasculitis group as compared to those in normal group. Treatment with aspirin significantly reduced the number of megakaryocytes and the formations of CFU-MK in bone marrow in this immune vasculitis model. Our study further demonstrated that IL-1β alone or in combination with TPO induced in-vitro CFU-MK formation. Using RT-PCR techniques, the mRNA of of IL-1 type I and type II receptors (IL-1 RI and RII) were detected in cultured CD61+ CD41+ cells and four megakaryocytic cell lines. The expression of IL-1 RI and RII was also confirmed by flow cytometry and immunofluorescence staining in bone marrow megakaryocytes. Moreover, the IL-1R bloker can reduced IL-1β induced megakaryopoiesis. This sudy showed that IL-1β may play an important role in the pathogenesis of immune vasculitis. Aspirin has anti-inflammation effects in this model which may be mediated via inhibiting megakaryopoiesis and platelet formation. Disclosures: No relevant conflicts of interest to declare.


1988 ◽  
Vol 23 (4) ◽  
pp. 179-186 ◽  
Author(s):  
W Zhang ◽  
K E Evans

A strain-based tensor polynomial failure criterion for anisotropic materials is proposed with explicit derivations given in both strain and stress space. The physical distinction between this strain-based criterion and the current stress-based tensorial criterion of Tsai and Wu, is clarified. The viability of the proposed criterion is shown by its application to a graphite—epoxy resin lamina under plane stress. The allowed loadings and failure envelope of this lamina are predicted. Comparison is made with existing failure criteria (both stress-based and strain-based), in particular the maximum stress, maximum strain, and Tsai-Wu criteria.


2021 ◽  
Vol 11 (8) ◽  
pp. 1565-1570
Author(s):  
Gaolin Wang ◽  
Bo Sun ◽  
Xiangpeng Meng ◽  
Bin Ge

SCN1A gene plays an indispensable role in several diseases. Bone marrow stromal stem cells (BMSCs) therapy is a potential target for treating epilepsy, but its therapeutic effect and mechanism is unclear. Our study aims to investigate the mechanism by how BMSCs affect epilepsy. Wistar rats were assigned into control group, model group (pilocarpine-induced TLE model), and BMSCs group followed by measuring the latency of field excitatory postsynaptic potential, pathological changes, SCN1A level by Real time PCR, NF-ĸB and TLR4 expression by Western blot, and HGMB1, TLR4, IL-1β and IL-6 secretion by ELISA. In model group, the incubation period of postsynaptic potential generation was significantly shortened and SCN1A level was significantly decreased, along with increased NF-ĸB expression and secretion of HMGB1, TLR-4, IL-1β and IL-6 (P < 0.05). After BMSCs treatment, the incubation period of postsynaptic potentials can be significantly prolonged and SCN1A was significantly upregulated, with ameliorated epilepsy injury and reduced secretion of related factors (P <0.05). Pilocarpine-induced TLE can reduce SCN1A expression and BMSCs therapy can up-regulate SCN1A expression by regulating NF-ĸB/HGMB1/TLR4 signaling pathway, thereby protecting neurons, reducing pathological damage, and ameliorating the development of epilepsy.


Blood ◽  
1993 ◽  
Vol 82 (3) ◽  
pp. 732-736 ◽  
Author(s):  
M Attal ◽  
F Huguet ◽  
H Rubie ◽  
JP Charlet ◽  
D Schlaifer ◽  
...  

Elevated levels of tumor necrosis factor alpha (TNF-alpha) have been reported to correlate with the development of transplant-related complications after bone marrow transplantation (BMT). In a recent phase I-II trial, oral administration of pentoxifylline (PTX), a xanthine derivative capable of downregulating TNF-alpha production in vitro, was reported to reduce morbidity and mortality in patients undergoing BMT. We conducted a prospective randomized trial of PTX therapy among 140 patients undergoing either allogeneic (n = 51) or autologous BMT (n = 89). Patients were randomized to receive (n = 70) or not receive (n = 70) oral PTX, 1,600 mg/d in four divided doses from day -8 until day + 100 post-BMT. The incidence of mucositis requiring morphine sulfate (MSO4) was similar in both groups (42.9%), with the mean number of days with MSO4 being 7.8 (SD = 3.4) in the PTX group versus 8.2 (SD = 3.4) in the control group (NS). The incidence of renal insufficiency was not affected by PTX administration (15.7% in the PTX group v 21.4% in the control group [NS]) and the highest serum creatinine value during the first 100 days post-BMT was 119 mumol/L (SD = 82.4) in the PTX group versus 103.9 mumol/L (SD = 57) in the control group (NS). The incidence of grade > or = 2 graft-versus-host disease was similar in each group (11/25 [44%] in the PTX group v 12/26 [46%] in the control group). No significant difference was observed in hematologic toxicity, transfusion requirements, duration of fever, and hepatic toxicity between the treatment groups. In conclusion, our study failed to show a prophylactic effect of PTX in transplant-related toxicities after BMT. On the basis of these findings, we cannot recommend that PTX be part of early mortality and morbidity prevention programs after BMT.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2866-2866
Author(s):  
Anna Lena Illert ◽  
Cornelius Miething ◽  
Rebekka Grundler ◽  
Manuel Schmidt ◽  
Andreas Burchert ◽  
...  

Abstract Interferon regulatory factors (IRF) are activating and/or repressing transcription factors induced by treatment with type I and II Interferon (IFN), other cytokines, receptor cross-linking and viral infection. In contrast to IRF-1 and IRF-2, which are widely expressed, IRF-4 and IRF-8 are tissue-restricted factors. IRF-8 is expressed mainly in cells of haematopoietic origin and has recently been shown to inhibit mitogenic activity of p210 Bcr/Abl-transformed myeloid progenitor cells by activating several genes that interfere with the c-Myc pathway. IRF-4 is most homologous with IRF-8 (approximately 70% overall homology) and its expression is highly restricted to lymphocytes of the B-cell type (pre-B, B, and plasma cells), mature T-cells and macrophages. Furthermore IRF-4 expression is significantly impaired in CML and AML patient samples predominately in T-cells. To examine a potential role of IRF-4 in Bcr/Abl mediated transformation we used a bone marrow transplant model (BMT). We transduced IRF-4 knockout (KO) bone marrow with retrovirus expressing p210 Bcr/Abl and transplanted it into lethally irradiated recipient C57/bl6 mice. For proper control we transplanted also wildtype (WT) bone marrow transduced with Bcr/Abl and mock transfected IRF-4 KO bone marrow (BM). All recipients transplanted with Bcr/Abl transduced BM (regardless of which IRF-4 KO or WT) developed rapidly a myeloproliferative disorder characterized by leukocytosis and expression of the myeloid lineage markers CD11b and Gr1. Surprisingly, IRF-4 KO Bcr/Abl infected BM recipient mice survived slightly longer than the control group transplanted with WT p210 BM (12 vs. 19 days). Histopathologic studies of the affected organs (spleen/lung) revealed extramedullary haematopoiesis in the spleens of both groups and a distinct infiltration of the tumor cells in the lung of WT Bcr/Abl transduced BM recipient mice, resulting in massive punctuated bleedings. Interestingly, preliminary analysis suggest a significantly reduced lung infiltration with almost no pulmonary bleedings in IRF-4 KO Bcr/Abl infected BM recipient mice, which we assume to be the reason for the differences in the overall survival. Taken together our data demonstrate that IRF-4 is not required for the induction of a myeloproliferative disorder by Bcr/Abl in vivo and for its ability to transform BM cells in vitro, but IRF-4 deficiency seems to have an impact on the fulminant pulmonary haemorrhage occurring in the murine CML-like disease.


1991 ◽  
Vol 9 (5) ◽  
pp. 865-870 ◽  
Author(s):  
M Attal ◽  
D Schlaifer ◽  
H Rubie ◽  
F Huguet ◽  
J P Charlet ◽  
...  

Gram-positive bacteria are the most commonly isolated organisms after bone marrow transplantation (BMT) and severe streptococcus septicemia has been reported. In order to evaluate the benefit of a gram-positive prophylaxis after BMT, we conducted a prospective, randomized trial of systemic vancomycin among 60 patients undergoing BMT for hematologic malignancies. Patients were randomized to receive (n = 30) or not receive (n = 30) prophylactic vancomycin 15 mg/kg every 12 hours from day -2 until resolution of neutropenia or until the first episode of fever. All patients were treated in laminar air-flow rooms, received sterile diet, total gut decontamination, and had central venous catheters placed surgically. Vancomycin was found to be highly effective in preventing gram-positive infections that occurred in 11 of 30 patients in the control group versus zero of 30 in the vancomycin group (P less than .002). All gram-positive infections occurring in the control group were symptomatic (nine septicemia and two local infections), and one patient with Streptococcus septicemia died with pneumonia. Thus, gram-positive prophylaxis was found to decrease infection morbidity after BMT. Moreover, the number of days with fever (P less than .001), and empiric antibiotic therapy (P less than .01) was reduced without added toxicity or cost. This study confirmed the high prevalence of gram-positive infections after BMT and emphasized the clinical benefits of an adapted prophylaxis.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Joseph Munoz ◽  
Shalom Siebert ◽  
Weimin Guo ◽  
Erin Lewis ◽  
Lijun Li ◽  
...  

Abstract Objectives Osteoporosis is a debilitating disease that increases with age and is characterized by increased bone fragility. However, dietary factors can influence the development of osteoporosis. For example, high fat diets (HFD) have been shown to have detrimental effects on bone density and quantity. However, the effects of HFD on bone microarchitecture have not been extensively studied. The architecture of the bone is important because it provides information regarding the quality of the bone and not just quantity. Therefore, the purpose of this study was to investigate the effects of HFD on bone microarchitecture in mice when compared to low fat diet fed mice. Methods Five-week-old mice were randomized into two different treatment groups, control and HFD (n = 6 per group). The control group were fed AIN-93 G growing rodent diet (20% protein, 65% carbohydrate (CHO), 15% fat) while the HFD group was fed a standard HFD ordered from Research Diets Inc. Cat #D12451M (20% protein, 35% CHO, 45% fat) for 20 weeks. After 20 weeks the animals were sacrificed and left tibial bone specimen were prepared for analysis via micro-computed tomography. Data were analyzed using one-way ANOVA to detect differences between groups. Results Mean values ± SEM for bone measurements (control, HFD) are as follows. Total Volume (TV) (6.04 mm3 ± 0.077, 6.16 mm3 ± 0.12 mm), bone volume (BV) (2.33 mm3 ± 0.054, 1.89 mm3 ± 0.06), BV/TV (0.386% ± 0.011, 0.31% ± 0.01), structural model index (SMI) (−0.687 ± 0.097, −0.35 ± 0.09), connective density (Conn.D) (775.83 ± 51.2, 693.8 ± 91.7), trabecular number (Tb.N) (7.52 mm ± 0.135, 6.23 mm ± 0.32), trabecular thickness (Tb.Th) (0.059 mm ± 0.0009, 0.056 mm ± 0.00069), and trabecular separation (Tb.Sp) (0.139 mm ± 0.003, 0.18 mm ± 0.0063). BV, BV/TV, Tb.N and Tb.Th values were all significantly higher (P < 0.05) in the control group versus the HFD group while SMI and Tb.Sp were significantly lower (P < 0.05). Conclusions These results agree with previous studies showing that HFD has detrimental effects on bone. This study demonstrated that HFD negatively impacts the microarchitecture of bone, specifically trabecular number, thickness, and separation which are important for overall structure, strength, and flexibility of bone. Future studies should focus on mechanisms underlying the role of HFD on the microarchitecture of bone. Funding Sources None


Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2398 ◽  
Author(s):  
Hongxing Zheng ◽  
Shanshan Qi ◽  
Chen Chen

Postmenopausal diabetic women have a high risk of fractures. Salidroside has preventive effects on estrogen deficiency-induced osteoporosis and has hypoglycemic effects on diabetes in rats. However, whether salidroside inhibits bone loss in postmenopausal diabetic patients is still unknown. Here, we established a rat model of osteoporosis to investigate the protective effects of salidroside on bone loss induced by ovariectomy combined with diabetes, also investigating the underlying mechanisms. Two-month-old female Sprague-Dawley rats were divided into three equal groups (10 rats in each group): control group (with sham operation, treated with drug vehicle); OVX/T1DM group (ovariectomized diabetic rats); OVX/T1DM-SAL group, comprising ovariectomized diabetic rats treated with salidroside (20 mg/kg body weight) by gavage. The results showed that after 60 consecutive days of treatment, the bone mineral density (BMD) of OVX/T1DM-SAL increased significantly compared with the OVX/T1DM group (p < 0.01). The level of serum bone turnover markers, including alkaline phosphatase (ALP), cross linked c-telopeptide of type I collagen (CTX-1), osteocalcin, N-terminal propeptide of type I procollagen (PINP), and tartrate-resistant acid phosphatase 5b (TRACP 5b) were all increased in the OVX/T1DM group compared with the control (p < 0.01), and those were decreased by salidroside treatment. Meanwhile, the bone histopathological changes were also attenuated, and the bone marrow adipogenesis was inhibited in salidroside treated rats. Moreover, protein and mRNA ratio of bone osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) was upregulated in ovariectomized diabetic rats by salidroside treatment. The results above indicated that the protective effect of salidroside on bone loss induced by ovariectomy and diabetes was mainly due to its ability to suppress bone turnover, inhibit bone marrow adipogenesis, and up-regulate the OPG/RANKL ratio.


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