scholarly journals Rapamycin Alleviates Cancellous Bone Loss and Cortical Bone Porosity in Ovariectomized Mice but Not Overall Biomechanical Performance

2021 ◽  
Author(s):  
Ruoyao Li ◽  
Junhao Liu ◽  
Zhiping Huang ◽  
Xiuhua Wu ◽  
Zhou Yang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Cortical Bone ◽  
Cancellous Bone ◽  
Sham Group ◽  
Biomechanical Properties ◽  
Bending Test ◽  
Tartrate Resistant Acid Phosphatase ◽  
Long Bones ◽  
Ovariectomized Mice ◽  
Vascular Canal

Abstract Background: Recent studies have shown that rapamycin (Rapa) rescues cancellous bone loss of osteoporosis models, but its effects on cortical bone and the biomechanical properties remain uncertain. This study was aimed to determine whether rapamycin improve the quality of long bones in ovariectomy (OVX)-induced osteoporosis.Methods: Thirty female C57BL/6J mice were randomly divided into Sham, OVX and OVX+Rapa group. Mice in the OVX+Rapa group were injected intraperitoneally with 1.5 mg/kg rapamycin daily after ovariectomy. After 12 weeks, the microstructures of femurs and the vascular canal porosity tibiae were analyzed by micro-CT. The compressive stiffness of the distal femurs was calculated with the micro-finite element method, and the bending strength of the tibiae was evaluated with a three-point bending test. Western blot of LC3, P62 was used to assess autophagy activity of bone. The number of osteoclasts was quantified by tartrate-resistant acid phosphatase (TRAP) staining. ELISA detected the concentration of bone-specific alkaline phosphatase (BALP) in serum.Results: OVX led to a decrease in cross-sectional areas of the mid-diaphyses and distal femoral cortical bones, increasing the cortical bone vascular canal porosity from 1.42% to 4.79%. The rapamycin reduced cancellous bone loss and decreased cortical bone vascular canal porosity by 3.9%, but further reduced the thickness of the distal femoral cortical bone by 16.7%, with no significant effect on the cortical bone in the mid-diaphyses. Compared to the Sham group, OVX mice showed a decrease in distal femoral stiffness to 6497 N/mm and a decrease in tibial maximum load to 6.08 N, while rapamycin intervention did not significantly improve the decreased biomechanical properties. Moreover, rapamycin remarkably reduced the TRAP-positive osteoclasts and the concentration of serum BALP by 80.6% and 30.8%, respectively. Autophagy was activated in the OVX group compared with the sham group.Conclusions: This study has demonstrated that rapamycin ameliorates cancellous bone loss and cortical bone porosity in ovariectomized mice but partly reduces the size of cortical bone, while has no effect on improving the biomechanical performance. Additionally, the present study also proved that OVX led to both cancellous and cortical bone loss, with attenuated biomechanical properties of long bones.

scholarly journals Rapamycin Alleviates Cancellous Bone Loss and Cortical Bone Porosity In Ovariectomized Mice But Not Overall Biomechanical Performance

2021 ◽  
Author(s):  
Ruoyao Li ◽  
Junhao Liu ◽  
Zhiping Huang ◽  
Xiuhua Wu ◽  
Qingan Zhu
Keyword(s):  
Bone Loss ◽  
Cortical Bone ◽  
Cancellous Bone ◽  
Sham Group ◽  
Biomechanical Properties ◽  
Bending Test ◽  
Tartrate Resistant Acid Phosphatase ◽  
Long Bones ◽  
Ovariectomized Mice ◽  
Vascular Canal

Abstract Background: Recent studies have shown that rapamycin (Rapa) rescues cancellous bone loss of osteoporosis models, but its effects on cortical bone and the biomechanical properties remain uncertain. This study was aimed to determine whether rapamycin improve the quality of long bones in ovariectomy (OVX)-induced osteoporosis.Methods: Thirty female C57BL/6J mice were randomly divided into Sham, OVX and OVX+Rapa group. Mice in the OVX+Rapa group were injected intraperitoneally with 1.5 mg/kg rapamycin daily after ovariectomy. After 12 weeks, the microstructures of femurs and the vascular canal porosity tibiae were analyzed by micro-CT. The compressive stiffness of the distal femurs was calculated with the micro-finite element method, and the bending strength of the tibiae was evaluated with a three-point bending test. Western blot of LC3, P62 was used to assess autophagy activity of bone. The number of osteoclasts was quantified by tartrate-resistant acid phosphatase (TRAP) staining. ELISA detected the concentration of bone-specific alkaline phosphatase (BALP) in serum.Results: OVX led to a decrease in cross-sectional areas of the mid-diaphyses and distal femoral cortical bones, increasing the cortical bone vascular canal porosity from 1.42% to 4.79%. The rapamycin reduced cancellous bone loss and decreased cortical bone vascular canal porosity by 3.9%, but further reduced the thickness of the distal femoral cortical bone by 16.7%, with no significant effect on the cortical bone in the mid-diaphyses. Compared to the Sham group, OVX mice showed a decrease in distal femoral stiffness to 6497 N/mm and a decrease in tibial maximum load to 6.08 N, while rapamycin intervention did not significantly improve the decreased biomechanical properties. Moreover, rapamycin remarkably reduced the TRAP-positive osteoclasts and the concentration of serum BALP by 80.6% and 30.8%, respectively. Autophagy was activated in the OVX group compared with the sham group.Conclusions: This study has demonstrated that rapamycin ameliorates cancellous bone loss and cortical bone porosity in ovariectomized mice but partly reduces the size of cortical bone, while has no effect on improving the biomechanical performance. Additionally, the present study also proved that OVX led to both cancellous and cortical bone loss, with attenuated biomechanical properties of long bones.

scholarly journals Porcupine inhibitors impair trabecular and cortical bone mass and strength in mice

2018 ◽  
Vol 238 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Thomas Funck-Brentano ◽  
Karin H Nilsson ◽  
Robert Brommage ◽  
Petra Henning ◽  
Ulf H Lerner ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Cortical Bone ◽  
Bone Strength ◽  
Bending Test ◽  
Bone Homeostasis ◽  
Mineral Density

WNT signaling is involved in the tumorigenesis of various cancers and regulates bone homeostasis. Palmitoleoylation of WNTs by Porcupine is required for WNT activity. Porcupine inhibitors are under development for cancer therapy. As the possible side effects of Porcupine inhibitors on bone health are unknown, we determined their effects on bone mass and strength. Twelve-week-old C57BL/6N female mice were treated by the Porcupine inhibitors LGK974 (low dose = 3 mg/kg/day; high dose = 6 mg/kg/day) or Wnt-C59 (10 mg/kg/day) or vehicle for 3 weeks. Bone parameters were assessed by serum biomarkers, dual-energy X-ray absorptiometry, µCT and histomorphometry. Bone strength was measured by the 3-point bending test. The Porcupine inhibitors were well tolerated demonstrated by normal body weight. Both doses of LGK974 and Wnt-C59 reduced total body bone mineral density compared with vehicle treatment (P < 0.001). Cortical thickness of the femur shaft (P < 0.001) and trabecular bone volume fraction in the vertebral body (P < 0.001) were reduced by treatment with LGK974 or Wnt-C59. Porcupine inhibition reduced bone strength in the tibia (P < 0.05). The cortical bone loss was the result of impaired periosteal bone formation and increased endocortical bone resorption and the trabecular bone loss was caused by reduced trabecular bone formation and increased bone resorption. Porcupine inhibitors exert deleterious effects on bone mass and strength caused by a combination of reduced bone formation and increased bone resorption. We suggest that cancer targeted therapies using Porcupine inhibitors may increase the risk of fractures.

scholarly journals Protective Effects of 2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-glucoside on Ovariectomy Induced Osteoporosis Mouse Model

2018 ◽  
Vol 19 (9) ◽  
pp. 2554 ◽  
Author(s):  
Su-Jin Kim ◽  
Yun-Ho Hwang ◽  
Seul-Ki Mun ◽  
Seong-Gyeol Hong ◽  
Kwang-Jin Kim ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Loss ◽  
Cell Damage ◽  
Bone Destruction ◽  
Tartrate Resistant Acid Phosphatase ◽  
Protective Effects ◽  
Micro Computed Tomography ◽  
Aging Effects ◽  
Polygonum Multiflorum ◽  
Ovariectomized Mice

2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-glucoside (TSG), an active polyphenolic component of Polygonum multiflorum, exhibits many pharmacological activities including antioxidant, anti-inflammation, and anti-aging effects. A previous study demonstrated that TSG protected MC3T3-E1 cells from hydrogen peroxide (H2O2) induced cell damage and the inhibition of osteoblastic differentiation. However, no studies have investigated the prevention of ovariectomy-induced bone loss in mice. Therefore, we investigated the effects of TSG on bone loss in ovariectomized mice (OVX). Treatment with TSG (1 and 3 μg/g; i.p.) for six weeks positively affected body weight, uterine weight, organ weight, bone length, and weight change because of estrogen deficiency. The levels of the serum biochemical markers of calcium (Ca), inorganic phosphorus (IP), alkaline phosphatase (ALP), and total cholesterol (TCHO) decreased in the TSG-treated mice when compared with the OVX mice. Additionally, the serum bone alkaline phosphatase (BALP) levels in the TSG-treated OVX mice were significantly increased compared with the OVX mice, while the tartrate-resistant acid phosphatase (TRAP) activity was significantly reduced. Furthermore, the OVX mice treated with TSG showed a significantly reduced bone loss compared to the untreated OVX mice upon micro-computed tomography (CT) analysis. Consequently, bone destruction in osteoporotic mice as a result of ovariectomy was inhibited by the administration of TSG. These findings indicate that TSG effectively prevents bone loss in OVX mice; therefore, it can be considered as a potential therapeutic for the treatment of postmenopausal osteoporosis.

scholarly journals ANTIOSTEOPOROTIC ACTIVITY OF ANTHRAQUINONE ISOLATED FROM MORINDA CITRIFOLIA FRUITS IN RATS

2016 ◽  
Vol 9 (5) ◽  
pp. 209 ◽  
Author(s):  
Abin Joy ◽  
Chaitra N ◽  
Ashok M ◽  
Handral M
Keyword(s):  
Bone Mineral Density ◽  
Bone Loss ◽  
Bone Strength ◽  
Bone Mineral ◽  
Morinda Citrifolia ◽  
Bending Test ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mineral Density ◽  
Femur Bone ◽  
Group I

ABSTRACTObjectives: This study was designed to investigate the antiosteoporotic activity of isolated anthraquinones from Morinda citrifolia fruit extract inovariectomy (OVX) induced osteoporotic rats.Methods: All the rats were divided into 4 groups (n=6 each). Group I (sham control) received vehicle, p.o., Group II OVX control (vehicle, p.o.),Group III was OVX+standard raloxifene (5.4 mg/kg, p.o.), and Group IV was OVX+Physcion (100 mg/kg, p.o.) for 90 days.Results: The daily oral administration of isolated compound physcion (100 mg/kg) for 12 weeks to the rats prevented OVX-induced osteoporosis.This was examined by serum biomarkers such as alkaline phosphatase, calcium, and tartrate resistant acid phosphatase and showed significanteffects (p<0.0001). The femur bone strength assessed by three-point bending test showed improved bone strength in physcion treated rats, andthis was supported by enhanced bone mineral density (p<0.05). The ash parameters of femur bone studied from physcion treated rats exhibited asignificant (p<0.0001) value of ash weight followed by ash calcium content. Further, femur bone histological examination revealed the protectiveeffect of the compound physcion (100 mg/kg) against OVX-induced bone loss in rats, where it showed mineralization of trabecular spaces, improvedbone compactness thereby intact bone architecture.Conclusion: This study concludes that the isolated anthraquinone physcion had a preventive effect against OVX-induced bone loss in rats.Keywords: Morinda citrifolia, Physcion, Osteoporosis, Bone mineral density, Ash mineral content.

scholarly journals Effects of treadmill with different intensities on bone quality and muscle properties in adult rats

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Zhehao Liu ◽  
Jiazi Gao ◽  
He Gong
Keyword(s):  
Cortical Bone ◽  
Soleus Muscle ◽  
Adult Male ◽  
Biomechanical Properties ◽  
Treadmill Running ◽  
Male Rats ◽  
Bending Test ◽  
Long Bone ◽  
Nanoindentation Test ◽  
Adult Rats

Abstract Background Bone is a dynamically hierarchical material that can be divided into length scales of several orders of magnitude. Exercise can cause bone deformation, which in turn affects bone mass and structure. This study aimed to study the effects of treadmill running with different intensities on the long bone integrity and muscle biomechanical properties of adult male rats. Methods Forty-eight 5-month-old male SD rats were randomly divided into 4 groups: i.e., sedentary group (SED), exercise with speed of 12 m/min group (EX12), 16 m/min group (EX16), and 20 m/min group (EX20). The exercise was carried out for 30 min every day, 5 days a week for 4 weeks. The femurs were examined using three-point bending test, microcomputer tomography scanning and nanoindentation test; the soleus muscle was dissected for tensile test; ALP and TRACP concentrations were measured by serum analysis. Results The failure load was significantly increased by the EX12 group, whereas the elastic modulus was not significantly changed. The microstructure and mineral densities of the trabecular and cortical bone were significantly improved by the EX12 group. The mechanical properties of the soleus muscle were significantly increased by treadmill exercise. Bone formation showed significant increase by the EX12 group. Statistically higher nanomechanical properties of cortical bone were detected in the EX12 group. Conclusion The speed of 12 m/min resulted in significant changes in the microstructure and biomechanical properties of bone; besides, it significantly increased the ultimate load of the soleus muscle. The different intensities of treadmill running in this study provide an experimental basis for the selection of exercise intensity for adult male rats.

scholarly journals The Ginsenoside Exhibits Antiosteoporosis Effects in Ketogenic-Diet-Induced Osteoporosis via Rebalancing Bone Turnover

2021 ◽  
Vol 11 ◽  
Author(s):  
Qi Liu ◽  
Jian Zhou ◽  
Zhou Yang ◽  
Chuhai Xie ◽  
Yan Huang ◽  
...  
Keyword(s):  
Bone Loss ◽  
Ketogenic Diet ◽  
Cancellous Bone ◽  
Volume Fraction ◽  
Cathepsin K ◽  
Tartrate Resistant Acid Phosphatase ◽  
Protective Effects ◽  
Bone Volume Fraction ◽  
Ppar Γ ◽  
Ginsenoside Rb2

Ginsenoside is widely used in China for therapeutic and healthcare practice. Ginsenoside-Rb2 shows the antiosteoporosis effects in ovariectomized rodents. However, the protective effects on osteoporosis induced by ketogenic diet (KD) remain unknown. Therefore, this study aimed at evaluating the effects of ginsenoside-Rb2 on KD-induced osteoporosis. Thirty mice were randomly divided into three groups: sham, KD, and KD + Rb2. Bone microstructures, biomechanical properties, concentrations of serum bone alkaline phosphatase (BALP) and tartrate-resistant acid phosphatase (TRACP), and protein expression of osteocalcin (OCN), peroxisome proliferation-activated receptor γ (PPAR-γ), cathepsin K, and TRAP were evaluated after a 12-week intervention. The results show that KD induced significant bone loss and biomechanical impairment. Ginsenoside-Rb2 attenuated significant bone loss and maintained biomechanics in cancellous bone. The bone volume fraction increased from 2.3 to 6.0% in the KD + Rb2 group than that in the KD group. Meanwhile, ginsenoside-Rb2 effectively maintained biomechanical strengths in cancellous bone, increased serum BALP and decreased TRACP, and upregulated OCN and downregulated TRAP, PPAR-γ, and cathepsin K in the KD mice. This study demonstrated that ginsenoside-Rb2 retards bone loss and maintains biomechanics with KD. The underlying mechanism might be that ginsenoside-Rb2 inhibits bone resorption process and induces osteogenic differentiation, providing evidence for ginsenoside as being an alternative option for osteoporosis induced by KD.

scholarly journals Mineralized bone loss at different sites in dialysis patients: implications for prevention.

1998 ◽  
Vol 9 (7) ◽  
pp. 1225-1233
Author(s):  
H C Schober ◽  
Z H Han ◽  
A J Foldes ◽  
M S Shih ◽  
D S Rao ◽  
...  
Keyword(s):  
Bone Loss ◽  
Cortical Bone ◽  
Bone Tissue ◽  
Cancellous Bone ◽  
Bone Volume ◽  
Ethnic Composition ◽  
Maintenance Hemodialysis ◽  
Appendicular Skeleton ◽  
Structural Abnormality ◽  
Patient Groups

To characterize the magnitude and location of mineralized bone loss, 40 patients (20 men, 20 women, 29 white, 11 black) with clinically significant renal osteodystrophy who could be unambiguously classified based on histologic criteria as having osteitis fibrosa (OF; 20 cases) or osteomalacia (OM; 20 cases) were studied; they had been on maintenance hemodialysis for 4.6 +/- 3.0 yr. One hundred forty-two healthy women of similar age and ethnic composition served as control subjects. In all subjects, the proportions of mineralized bone, osteoid, and porosity (nonbone soft tissue) were measured separately in cortical and cancellous bone tissue, from intact full-thickness biopsies of the ilium, representative of the axial skeleton. The results were related to the volumes of cortical and cancellous bone tissue separately and to the volume of the entire biopsy core. Approximately three-quarters of the patients had measurements in the appendicular skeleton by single photon absorptiometry of the radius and morphometry of the metacarpal. Disease effects did not differ significantly between ethnic groups. Mineralized cortical bone volume (per unit of core volume) was reduced by approximately 45% in both patient groups. Mineralized cancellous bone volume was significantly increased by 36% in the patients with OF and nonsignificantly reduced by 9% in the patients with OM; however, the reduction in the latter patients was significant in relation to tissue volume. The combined total deficit for both types of iliac bone was approximately 20% in the patients with OF and approximately 40% in the patients with OM. Significant reductions in appendicular cortical bone were demonstrated in both patient groups at both measurement sites. Regardless of the current histologic classification, the major structural abnormality in the skeleton is generalized thinning of cortical bone due to increased net endocortical resorption, the most characteristic effect on bone of hyperparathyroidism. Protection of the skeleton from the adverse consequences of renal failure will require therapeutic intervention in patients with no symptoms of either renal or bone disease.

scholarly journals The Lyme Disease Pathogen Borrelia burgdorferi Infects Murine Bone and Induces Trabecular Bone Loss

2016 ◽  
Vol 85 (2) ◽  
Author(s):  
Tian Tian Tang ◽  
Lucia Zhang ◽  
Anil Bansal ◽  
Marc Grynpas ◽  
Tara J. Moriarty
Keyword(s):  
Lyme Disease ◽  
Bone Loss ◽  
Borrelia Burgdorferi ◽  
Trabecular Bone ◽  
Copy Number ◽  
Bone Microarchitecture ◽  
Biomechanical Properties ◽  
Long Bones ◽  
Mineral Density ◽  
Content Type

ABSTRACT Lyme disease is caused by members of the Borrelia burgdorferi sensu lato species complex. Arthritis is a well-known late-stage pathology of Lyme disease, but the effects of B. burgdorferi infection on bone at sites other than articular surfaces are largely unknown. In this study, we investigated whether B. burgdorferi infection affects bone health in mice. In mice inoculated with B. burgdorferi or vehicle (mock infection), we measured the presence of B. burgdorferi DNA in bones, bone mineral density (BMD), bone formation rates, biomechanical properties, cellular composition, and two- and three-dimensional features of bone microarchitecture. B. burgdorferi DNA was detected in bone. In the long bones, increasing B. burgdorferi DNA copy number correlated with reductions in areal and trabecular volumetric BMDs. Trabecular regions of femora exhibited significant, copy number-correlated microarchitectural disruption, but BMD, microarchitectural, and biomechanical properties of cortical bone were not affected. Bone loss in tibiae was not due to increased osteoclast numbers or bone-resorbing surface area, but it was associated with reduced osteoblast numbers, implying that bone loss in long bones was due to impaired bone building. Osteoid-producing and mineralization activities of existing osteoblasts were unaffected by infection. Therefore, deterioration of trabecular bone was not dependent on inhibition of osteoblast function but was more likely caused by blockade of osteoblastogenesis, reduced osteoblast survival, and/or induction of osteoblast death. Together, these data represent the first evidence that B. burgdorferi infection induces bone loss in mice and suggest that this phenotype results from inhibition of bone building rather than increased bone resorption.

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