Combination of Weight-Bearing Training and Anti-MSTN Polyclonal Antibody Improve Bone Quality In Rats

2016 ◽  
Vol 26 (6) ◽  
pp. 516-524 ◽  
Author(s):  
Liang Tang ◽  
Xiaohang Gao ◽  
Xiaoying Yang ◽  
Didi Zhang ◽  
Xiaojun Zhang ◽  
...  

Weight-bearing exercise is beneficial to bone health. Myostatin (MSTN) deficiency has a positive effect on bone formation. We wondered if a combination of weight-bearing training and polyclonal antibody for MSTN (MsAb) would augment bone formation to a greater degree than single treatment. In this study, rats were randomly assigned to four groups: Control, weight-bearing training (WT), MsAb, and WT+MsAb. The trained rats ran at 15 m/min bearing with 35% of their body weight, 40 min/day (2 min of running followed by 2 min of rest), 6 days/week, for 8 weeks. The rats with MsAb were injected once a week with MsAb for 8 weeks. MicroCT analysis showed that compared with the MsAb group, WT+MsAb significantly enhanced cortical bone mineral density (BMD) (p < .01), bone volume over total volume (BV/TV) (p < .01), trabecular thickness (p < .05), and reduced trabecular separation (Tb.Sp) (p < .01). Compared with the WT group, WT+MsAb significantly increased trabecular BMD (p < .05), BV/TV (p < .05), and decreased Tb.Sp (p < .05). Three-point bending test demonstrated that MsAb failed to improve bone biomechanical properties (p > .05), weight-bearing training significantly increased energy absorption (p < .05) and elastic modulus (p < .05). However, when they combined, biomechanical properties including maximum load (p < .05), stiffness (p < .05), elastic modulus (p < .01) and energy absorption (p < .01) were all significantly enhanced. In conclusion, the combination of weight-bearing training and MsAb have a greater positive effect on bone than treatment with either MsAb or weight-bearing training alone, suggesting that resistance training in combination with MSTN antagonists could be an effective approach for improving bone health and reducing osteoporosis risk.

2020 ◽  
Author(s):  
Bo Liu ◽  
Chenchen Ji ◽  
Yijie Shao ◽  
Ting Liang ◽  
Jiaheng He ◽  
...  

Abstract Background Etoricoxib, a selective Cyclooxygenase-2 (COX-2) inhibitor, is commonly used in osteoarthritis (OA) for pain relief. The purpose of our study was to investigate the effects of Etoricoxib on mouse subchondral bone in early OA. Methods OA was induced via destabilization of the medial meniscus (DMM) in C57BL/6J mice. After surgery, the mice were randomly and equally divided into five groups: a sham-operated control group (Sham group), an osteoarthritis (OA) group (DMM group), an OA treated with Etoricoxib 5mg/kg (DMM+E5) group, an OA treated with Etoricoxib 10mg/kg (DMM+E10) group, and an OA treated with Etoricoxib 20mg/kg (DMM+E20) group. Mice in the Sham group and DMM group were injected with a similar dose of vehicle (40% ethyl alcohol–saline solution). Four weeks after treatment, mice were euthanized. Micro computed tomography (Mirco-CT) analysis, Safranin O-Fast Green staining, hematoxylin and eosin (HE) staining were performed to evaluate morphological and structural changes. In addition, atomic force microscopy (AFM) analysis was performed to evaluate changes in the elastic modulus. Furthermore, changes in microstructure were detected by scanning electron microscopy (SEM). Results Etoricoxib inhibited osteophyte formation in the subchondral bone. However, it also reduced the bone volume fraction (BV/TV), lowered trabecular thickness (Tb.Th), and more microfractures and pores were observed in the subchondral bone. Moreover, Etoricoxib reduced the elastic modulus of subchondral bone. Furthermore, exposure to Etoricoxib further increased the empty/total osteocyte ratio of the subchondral bone. In cartilage and synovium, Etoricoxib did not significantly change the Osteoarthritis Research Society International (OARSI) score, the modified Mankin score, and the synovialitis-score versus the DMM group. Conclusion Although Etoricoxib can relieve the pain induced by OA, it can also change microstructures and biomechanical properties of the subchondral bone at the early stage of OA, cause osteoporotic changes in subchondral bone structure, increase the risk of fragile fracture of subchondral bone.


Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 424
Author(s):  
Radoslaw Piotr Radzki ◽  
Marek Bienko ◽  
Dariusz Wolski ◽  
Monika Ostapiuk ◽  
Pawel Polak ◽  
...  

Our study aimed to verify the hypothesis of the existence of a programming effect of parental obesity on the growth, development and mineralization of the skeletal system in female and male rat offspring on the day of weaning. The study began with the induction of obesity in female and male rats of the parental generation, using a high-energy diet (group F). Females and males of the control group received the standard diet (group S). After 90 days of dietary-induced obesity, the diet in group F was changed into the standard. Rats from groups F and S were mated to obtain offspring which stayed with their mothers until 21 days of age. Tibia was tested using dual-energy X-ray absorptiometry (DXA), peripheral quantitative computed tomography (pQCT), micro-computed tomography (µCT) and mechanical strength using the three-point bending test. Biochemical analysis of blood serum bone metabolism markers was performed. DXA analysis showed higher tibia bone mineral content (BMC) and area. pQCT measurements of cortical and trabecular tissue documented the increase of the volumetric bone mineral density and BMC of both bone compartments in offspring from the F group, while µCT of the trabecular tissue showed an increase in trabecular thickness and a decrease of its separation. Parental obesity, hence, exerts a programming influence on the development of the skeletal system of the offspring on the day of the weaning, which was reflected in the intensification of mineralization and increased bone strength.


Cellulose ◽  
2021 ◽  
Vol 28 (15) ◽  
pp. 9751-9768
Author(s):  
Teija Laukala ◽  
Sami-Seppo Ovaska ◽  
Ninja Kerttula ◽  
Kaj Backfolk

AbstractThe effects of bio-based strengthening agents and mineral filling procedure on the 3D elongation of chemi-thermomechanical pulp (CTMP) handsheets with and without mineral (PCC) filling have been investigated. The 3D elongation was measured using a press-forming machine equipped with a special converting tool. The strength of the handsheets was altered using either cationic starch or microfibrillated cellulose. Precipitated calcium carbonate (PCC) was added to the furnish either as a slurry or by precipitation of nano-sized PCC onto and into the CTMP fibre. The 3D elongation of unfilled sheets was increased by the dry-strengthening agents, but no evidence on the theorised positive effect of mineral fill on 3D elongation was seen in either filling method. The performance of the strengthening agent depended on whether the PCC was as slurry or as a precipitated PCC-CTMP. The starch was more effective with PCC-CTMP than when the PCC was added directly as a slurry to the furnish, whereas the opposite was observed with microfibrillated cellulose. The 3D elongation correlated positively with the tensile strength, bursting strength, tensile stiffness, elastic modulus and bending stiffness, even when the sheet composition was varied, but neither the strengthening agent nor the method of PCC addition affected the 3D elongation beyond what was expectable based on the tensile strength of the sheets. Finally, mechanisms affecting the properties that correlated with the 3D elongation are discussed.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jingyan Fu ◽  
Matthew Goldsmith ◽  
Sequoia D. Crooks ◽  
Sean F. Condon ◽  
Martin Morris ◽  
...  

AbstractAnimals in space exploration studies serve both as a model for human physiology and as a means to understand the physiological effects of microgravity. To quantify the microgravity-induced changes to bone health in animals, we systematically searched Medline, Embase, Web of Science, BIOSIS, and NASA Technical reports. We selected 40 papers focusing on the bone health of 95 rats, 61 mice, and 9 rhesus monkeys from 22 space missions. The percentage difference from ground control in rodents was –24.1% [Confidence interval: −43.4, −4.9] for trabecular bone volume fraction and –5.9% [−8.0, −3.8] for the cortical area. In primates, trabecular bone volume fraction was lower by –25.2% [−35.6, −14.7] in spaceflight animals compared to GC. Bone formation indices in rodent trabecular and cortical bone were significantly lower in microgravity. In contrast, osteoclast numbers were not affected in rats and were variably affected in mice. Thus, microgravity induces bone deficits in rodents and primates likely through the suppression of bone formation.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 979
Author(s):  
Patricia Garcia-Garcia ◽  
Ricardo Reyes ◽  
José Antonio Rodriguez ◽  
Tomas Martín ◽  
Carmen Evora ◽  
...  

Biomaterials-mediated bone formation in osteoporosis (OP) is challenging as it requires tissue growth promotion and adequate mineralization. Based on our previous findings, the development of scaffolds combining bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 10 (MMP-10) shows promise for OP management. To test our hypothesis, scaffolds containing BMP-2 + MMP-10 at variable ratios or BMP-2 + Alendronate (ALD) were prepared. Systems were characterized and tested in vitro on healthy and OP mesenchymal stem cells and in vivo bone formation was studied on healthy and OP animals. Therapeutic molecules were efficiently encapsulated into PLGA microspheres and embedded into chitosan foams. The use of PLGA (poly(lactic-co-glycolic acid)) microspheres as therapeutic molecule reservoirs allowed them to achieve an in vitro and in vivo controlled release. A beneficial effect on the alkaline phosphatase activity of non-OP cells was observed for both combinations when compared with BMP-2 alone. This effect was not detected on OP cells where all treatments promoted a similar increase in ALP activity compared with control. The in vivo results indicated a positive effect of the BMP-2 + MMP-10 combination at both of the doses tested on tissue repair for OP mice while it had the opposite effect on non-OP animals. This fact can be explained by the scaffold’s slow-release rate and degradation that could be beneficial for delayed bone regeneration conditions but had the reverse effect on healthy animals. Therefore, the development of adequate scaffolds for bone regeneration requires consideration of the tissue catabolic/anabolic balance to obtain biomaterials with degradation/release behaviors suited for the existing tissue status.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Haoliang Huang ◽  
Guang Ye

In this research, self-healing due to further hydration of unhydrated cement particles is taken as an example for investigating the effects of capsules on the self-healing efficiency and mechanical properties of cementitious materials. The efficiency of supply of water by using capsules as a function of capsule dosages and sizes was determined numerically. By knowing the amount of water supplied via capsules, the efficiency of self-healing due to further hydration of unhydrated cement was quantified. In addition, the impact of capsules on mechanical properties was investigated numerically. The amount of released water increases with the dosage of capsules at different slops as the size of capsules varies. Concerning the best efficiency of self-healing, the optimizing size of capsules is 6.5 mm for capsule dosages of 3%, 5%, and 7%, respectively. Both elastic modulus and tensile strength of cementitious materials decrease with the increase of capsule. The decreasing tendency of tensile strength is larger than that of elastic modulus. However, it was found that the increase of positive effect (the capacity of inducing self-healing) of capsules is larger than that of negative effects (decreasing mechanical properties) when the dosage of capsules increases.


2021 ◽  
pp. 073168442199086
Author(s):  
Yunfei Qu ◽  
Dian Wang ◽  
Hongye Zhang

The double V-wing honeycomb can be applied in many fields because of its lower mass and higher performance. In this study, the volume, in-plane elastic modulus and unit cell area of the double V-wing honeycomb were analytically derived, which became parts of the theoretical basis of the novel equivalent method. Based on mass, plateau load, in-plane elastic modulus, compression strain and energy absorption of the double V-wing honeycomb, a novel equivalent method mapping relationship between the thickness–width ratio and the basic parameters was established. The various size factor of the equivalent honeycomb model was denoted as n and constructed by the explicit finite element analysis method. The mechanical properties and energy absorption performance for equivalent honeycombs were investigated and compared with hexagonal honeycombs under dynamic impact. Numerical results showed a well coincidence for each honeycomb under dynamic impact before 0.009 s. Honeycombs with the same thickness–width ratio had similar mechanical properties and energy absorption characteristics. The equivalent method was verified by theoretical analysis, finite element analysis and experimental testing. Equivalent honeycombs exceeded the initial honeycomb in performance efficiency. Improvement of performance and weight loss reached 173.9% and 13.3% to the initial honeycomb. The double V-wing honeycomb possessed stronger impact resistance and better load-bearing capacity than the hexagonal honeycomb under impact in this study. The equivalent method could be applied to select the optimum honeycomb based on requirements and improve the efficiency of the double V-wing honeycomb.


2012 ◽  
Vol 302 (10) ◽  
pp. E1183-E1188 ◽  
Author(s):  
Nabanita S. Datta ◽  
Tareq A. Samra ◽  
Abdul B. Abou-Samra

Activation of G protein-coupled receptors by agonists leads to receptor phosphorylation, internalization of ligand receptor complexes, and desensitization of hormonal response. The role of parathyroid hormone (PTH) receptor 1, PTHR1, is well characterized and known to regulate cellular responsiveness in vitro. However, the role of PTHR1 phosphorylation in bone formation is yet to be investigated. We have previously demonstrated that impaired internalization and sustained cAMP stimulation of phosphorylation-deficient (PD) PTHR1 leads to exaggerated cAMP response to subcutaneous PTH infusion in a PD knockin mouse model. To understand the physiological role of receptor internalization on PTH bone anabolic action, we examined bone parameters of wild-type (WT) and PD knockin female and male mice following PTH treatment. We found a decrease in total and diaphyseal bone mineral density in female but not in male PD mice compared with WT controls at 3–6 mo of age. This effect was attenuated at older age groups. PTH administration displayed increased bone volume and trabecular thickness in the vertebrae and distal femora of both WT and PD animals. These results suggest that PTHR1 phosphorylation does not play a major role in the anabolic action of PTH.


2013 ◽  
Vol 58 (4) ◽  
pp. 427-434 ◽  
Author(s):  
Carlos E. Bozzini ◽  
Graciela M. Champin ◽  
Rosa M. Alippi ◽  
Clarisa Bozzini

2009 ◽  
Vol 297 (6) ◽  
pp. C1358-C1367 ◽  
Author(s):  
Gerald J. Atkins ◽  
Katie J. Welldon ◽  
Asiri R. Wijenayaka ◽  
Lynda F. Bonewald ◽  
David M. Findlay

The vitamin K family members phylloquinone (vitamin K1) and the menaquinones (vitamin K2) are under study for their roles in bone metabolism and as potential therapeutic agents for skeletal diseases. We have investigated the effects of two naturally occurring homologs, phytonadione (vitamin K1) and menatetrenone (vitamin K2), and those of the synthetic vitamin K, menadione (vitamin K3), on human primary osteoblasts. All homologs promoted in vitro mineralization by these cells. Vitamin K1-induced mineralization was highly sensitive to warfarin, whereas that induced by vitamins K2 and K3 was less sensitive, implying that γ-carboxylation and other mechanisms, possibly genomic actions through activation of the steroid xenobiotic receptor, are involved in the effect. The positive effect on mineralization was associated with decreased matrix synthesis, evidenced by a decrease from control in expression of type I collagen mRNA, implying a maturational effect. Incubation in the presence of vitamin K2 or K3 in a three-dimensional type I collagen gel culture system resulted in increased numbers of cells with elongated cytoplasmic processes resembling osteocytes. This effect was not warfarin sensitive. Addition of calcein to vitamin K-treated cells revealed vitamin K-dependent deposition of mineral associated with cell processes. These effects are consistent with vitamin K promoting the osteoblast-to-osteocyte transition in humans. To test whether vitamin K may also act on mature osteocytes, we tested the effects of vitamin K on MLO-Y4 cells. Vitamin K reduced receptor activator of NF-κB ligand expression relative to osteoprotegerin by MLO-Y4 cells, an effect also seen in human cultures. Together, our findings suggest that vitamin K promotes the osteoblast-to-osteocyte transition, at the same time decreasing the osteoclastogenic potential of these cells. These may be mechanisms by which vitamin K optimizes bone formation and integrity in vivo and may help explain the net positive effect of vitamin K on bone formation.


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