Age-related trabecular bone loss is associated with a decline in serum Galectin-1 level

Abstract Background Senile osteoporosis with age-related bone loss is diagnosed depending on radiographic changes of bone and bone mineral density (BMD) measurement. However, radiographic alterations are usually signs of medium-late stage osteoporosis. Therefore, biomarkers have been proposed as indicators of bone loss. In the current study, Galectin-1 (Gal-1) showed age-related decline in mice serum. The role of Gal-1 in osteoporosis has not been investigated so far. Hence, the current study illustrated the relationship of serum Gal-1 level with bone loss. Methods We employed 6- and 18-month-old mice to establish an animal model of age-related trabecular bone loss, whose bone density and microstructure were investigated by micro-CT. ELISA was used to measure the levels of Gal-1 in serum. The correlation analysis was performed to illustrate the relationship between serum Gal-1 levels and trabecular bone loss. In addition, immunohistochemistry was used to investigate the abundance of Gal-1 in bone marrow of mice. ELISA and western blot were performed to measure the secretion ability and protein expression of Gal-1 in bone marrow stromal cells (BMSC), hematopoietic stem cells (HSC) and myeloid progenitor (MP) respectively. Flow cytometry was used to measure BMSC number in bone marrow. Finally, male volunteers with age-related BMD decrease were recruited and the relationship between serum Gal-1 and BMD was analyzed. Results Gal-1 showed age-related decline in mice serum. Serum Gal-1 was positively associated with BV/TV of femur, tibia and L1 vertebrae in mice. BMSC secreted more Gal-1 compared with HSC and MP. BMSC number in bone marrow was significantly lower in aged mice compared with young mice. Significant attenuation of Gal-1 protein expression was observed in BMSC and HSC from aged mice compared with young mice. Further, we found a decline in serum Gal-1 levels in men with age-related BMD decrease. There was positive correlation between BMD and serum Gal-1 levels in these men. Conclusions Age-related trabecular bone loss is associated with a decline in serum Gal-1 level in mice and men. Our study suggested Gal-1 had great potential to be a biomarker for discovering BMSC senescence, diagnosing early osteoporosis and monitoring trabecular bone loss.

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Blackcurrant Supplementation Improves Trabecular Bone Mass in Young but Not Aged Mice

Nutrients ◽

10.3390/nu10111671 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1671 ◽

Cited By ~ 4

Author(s):

Junichi Sakaki ◽

Melissa Melough ◽

Sang Lee ◽

Judy Kalinowski ◽

Sung Koo ◽

...

Keyword(s):

Bone Resorption ◽

Bone Loss ◽

Bone Mass ◽

Trabecular Bone ◽

Chow Diet ◽

Type I ◽

Aged Mice ◽

Age Related ◽

Standard Chow Diet ◽

Young Mice

Due to deleterious side effects of currently available medications, the search for novel, safe, and effective preventive agents for improving bone health in aging continues and is urgently needed. This study aimed to determine whether dietary blackcurrants (BC), an anthocyanin-rich berry, can improve bone mass in a mouse model of age-related bone loss. Thirty-five female C57BL/6J mice, 3 months old (n = 20) and 18 months old (n = 15), were randomized to consume either a standard chow diet or a standard chow diet with 1% (w/w) BC for four months. Dual-energy X-ray absorptiometry, Micro computed tomography (µCT), and histomorphometric analyses were conducted to assess bone parameters on femurs. Biochemical assays were conducted to determine bone resorption, antioxidant activity, and inflammation in humerus homogenates. Trabecular bone volume (BV/TV) was significantly lower in aged mice compared to young mice (young control, 3.7 ± 0.4% vs aged control, 1.5 ± 0.5%, mean ± SEM (standard error of mean), p < 0.01; young BC, 5.3 ± 0.6% vs aged BC, 1.1 ± 0.3%, p < 0.001). µCT analysis revealed that BC supplementation increased trabecular BV/TV in young mice by 43.2% (p < 0.05) compared to controls. Histomorphometric analysis revealed a 50% increase, though this effect was not statistically significant (p = 0.07). The osteoblast surface increased by 82.5% in aged mice with BC compared to controls (p < 0.01). In humerus homogenates of young mice, BC consumption reduced C-telopeptide of type I collagen by 12.4% (p < 0.05) and increased glutathione peroxidase by 96.4% (p < 0.05). In humerus homogenates of aged mice, BC consumption increased catalase by 12% (p = 0.09). Aged mice had significantly elevated concentrations of tumor necrosis factor α (TNF-α), a pro-inflammatory cytokine contributing to bone resorption, which was reduced by 43.3% with BC consumption (p = 0.06). These results suggest that early consumption of BC may protect from aging-associated bone loss.

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The plate-to-rod transition in trabecular bone loss is elusive

Royal Society Open Science ◽

10.1098/rsos.201401 ◽

2021 ◽

Vol 8 (6) ◽

pp. 201401

Author(s):

A. A. Felder ◽

S. Monzem ◽

R. De Souza ◽

B. Javaheri ◽

D. Mills ◽

...

Keyword(s):

Bone Loss ◽

Trabecular Bone ◽

Volume Fraction ◽

Bone Volume ◽

Continuous Measure ◽

Bone Volume Fraction ◽

Trabecular Bone Loss ◽

Mouse Tibia ◽

Disease Stages ◽

The Relationship

Changes in trabecular micro-architecture are key to our understanding of osteoporosis. Previous work focusing on structure model index (SMI) measurements have concluded that disease progression entails a shift from plates to rods in trabecular bone, but SMI is heavily biased by bone volume fraction. As an alternative to SMI, we proposed the ellipsoid factor (EF) as a continuous measure of local trabecular shape between plate-like and rod-like extremes. We investigated the relationship between EF distributions, SMI and bone volume fraction of the trabecular geometry in a murine model of disuse osteoporosis as well as from human vertebrae of differing bone volume fraction. We observed a moderate shift in EF median (at later disease stages in mouse tibia) and EF mode (in the vertebral samples with low bone volume fraction) towards a more rod-like geometry, but not in EF maximum and minimum. These results support the notion that the plate to rod transition does not coincide with the onset of bone loss and is considerably more moderate, when it does occur, than SMI suggests. A variety of local shapes not straightforward to categorize as rod or plate exist in all our trabecular bone samples.

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Protective Effects of Curcumin and Broccoli Seed Extract Against Age-Related Bone Loss in Mice

Current Developments in Nutrition ◽

10.1093/cdn/nzaa040_046 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 46-46

Author(s):

Jing Li ◽

Dong Zhang ◽

Yiping Ren ◽

Zhongdong Qiao ◽

Doug Stevenson ◽

...

Keyword(s):

Bone Loss ◽

Seed Extract ◽

Control Group ◽

Protective Effects ◽

Trabecular Thickness ◽

Time Points ◽

Aged Mice ◽

Funding Sources ◽

Age Related ◽

Young Mice

Abstract Objectives Age-related bone loss occurs in both men and women, and is the leading cause of elderly disability. An age-related bone loss model was established in mice to investigate the protective effects of curcumin and broccoli seed extract. Methods 20 young (6-month-old) male C57BL/6 J mice after administration with vehicle once daily were sacrificed at four time points: day 0, 30, 60 and 90. 8 out of the 109 aged (18-month-old) male C57BL/6 J mice were sacrificed at the beginning and used as control. The rest of these aged mice were then randomly divided into four groups: one group served as control (vehicle), the other three groups were administrated with curcumin (CMN) and/or broccoli seed extract (BSE) by oral gavage. Mice in each group were sacrificed at four time points: day 0, 30, 60 and 90. L2 vertebrae of mice were fixed with paraformaldehyde and scanned with a Scanco Medical μCT40 scanner. Quantitative analyses of bone volume (BV), tissue volume (TV), trabecular number (Tb.N), trabecular thickness (Tb.Th) and trabecular spacing (Tb.Sp) were performed with the Scanco Medical's software. Results BV/TV of the young mice group were significantly higher compared to the aged mice group at all four time points. Similarly, Tb.N and Tb.Th were also higher in the young mice group compared to the aged mice group. In contrast, Tb.Sp was lower in the young mice group. When comparing different groups in the aged mice, we found that mice administered with CMN had a higher BV/TV value compared to the mice in the control group at all three time points. Such a difference is significant by day 30. The mice administered with combined CMN and BSE also showed significant increase in BV/TV on day 30. For Tb.N, both mice administered with either CMN or BSE had higher values at all three time points. But no obvious difference in Tb.N was found for mice administered with combined CMN and BSE. For Tb.Th, both mice administered with CMN and with combined CMN and BSE had higher values compared to the control. For Tb.Sp, both mice administered with either CMN or BSE had lower values compared to the control. Conclusions This study showed that curcumin could slow down bone loss in the mouse model. There is no obvious positive effect with broccoli seed extract or with curcumin and broccoli seed extract combined. The curcumin used in this study may shed light on the alleviation of bone loss in humans. Funding Sources Nu Skin Enterprises.

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Protocatechuic Acid Attenuates Trabecular Bone Loss in Ovariectomized Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/7280342 ◽

2018 ◽

Vol 2018 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Seon-A Jang ◽

Hae Seong Song ◽

Jeong Eun Kwon ◽

Hyun Jin Baek ◽

Hyun Jung Koo ◽

...

Keyword(s):

Bone Marrow ◽

Bone Loss ◽

Trabecular Bone ◽

Protocatechuic Acid ◽

Bone Marrow Cells ◽

Biomechanical Properties ◽

Primary Osteoporosis ◽

Nuclear Factor ◽

Trabecular Bone Loss ◽

Marrow Cells

Primary osteoporosis is a disease related to excessive bone resorption due to estrogen insufficiency that occurs postmenopause. Protocatechuic acid (PCA), or 3,4-dihydroxybenzoic acid, is a common compound present in numerous plants. Although numerous biological activities of PCA have been identified, its antiosteoporotic function has not been well established. In this study, the antiosteoporotic activity of PCA supplementation was determined in ovariectomized (OVX) female ICR mice at 12 weeks after OVX. The biomechanical properties of a bone were evaluated by microcomputed tomography. The signaling molecules associated with osteoclast differentiation were determined in bone marrow cells through immunoblot or RT-PCR. Oral supplementation with PCA (20 mg/kg/day) significantly ameliorated the OVX-mediated stimulation of osteoclast activity based on decreases in serum levels of receptor activator of nuclear factor κB ligand (RANKL), osteocalcin, and bone alkaline phosphatase and increase in serum osteoprotegerin (each group, n=6; p<0.05). In addition, the OVX-induced decreases in mRNA expression levels of cathepsin K, calcitonin receptor, nuclear factor of activated T cell cytoplasmic 1 (NFATc1), and tumor necrosis factor (TNF) receptor-associated factor-6 (TRAF6) in bone marrow cells were significantly attenuated (each group, n=6; p<0.05). Finally, the loss of trabecular bone and changes in biomechanical properties of a bone were significantly improved by supplementation with 20 mg/kg PCA (each group, n=6; p<0.05). Collectively, our results show that PCA supplement suppressed trabecular bone loss in OVX mice and therefore might be an effective alternative approach for preventing the progression of postmenopausal osteoporosis.

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Modeling the Mechanical Consequences of Age-Related Trabecular Bone Loss by XFEM Simulation

Computational and Mathematical Methods in Medicine ◽

10.1155/2016/3495152 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Ruoxun Fan ◽

He Gong ◽

Xianbin Zhang ◽

Jun Liu ◽

Zhengbin Jia ◽

...

Keyword(s):

Mechanical Properties ◽

Bone Loss ◽

Trabecular Bone ◽

Bone Age ◽

The Elderly ◽

Extended Finite Element ◽

Age Related ◽

Trabecular Bone Loss ◽

Complete Failure ◽

Fracture Processes

The elderly are more likely to suffer from fracture because of age-related trabecular bone loss. Different bone loss locations and patterns have different effects on bone mechanical properties. Extended finite element method (XFEM) can simulate fracture process and was suited to investigate the effects of bone loss on trabecular bone. Age-related bone loss is indicated by trabecular thinning and loss and may occur at low-strain locations or other random sites. Accordingly, several ideal normal and aged trabecular bone models were created based on different bone loss locations and patterns; then, fracture processes from crack initiation to complete failure of these models were observed by XFEM; finally, the effects of different locations and patterns on trabecular bone were compared. Results indicated that bone loss occurring at low-strain locations was more detrimental to trabecular bone than that occurring at other random sites; meanwhile, the decrease in bone strength caused by trabecular loss was higher than that caused by trabecular thinning, and the effects of vertical trabecular loss on mechanical properties were more severe than horizontal trabecular loss. This study provided a numerical method to simulate trabecular bone fracture and distinguished different effects of the possible occurrence of bone loss locations and patterns on trabecular bone.

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Age dependence of systemic bone loss and recovery following femur fracture in mice

10.1101/291906 ◽

2018 ◽

Cited By ~ 1

Author(s):

Armaun J. Emami ◽

Chrisoula A. Toupadakis ◽

Stephanie M. Telek ◽

David P. Fyhrie ◽

Clare E. Yellowley ◽

...

Keyword(s):

Bone Loss ◽

Fracture Risk ◽

Trabecular Bone ◽

Voluntary Movement ◽

Whole Body ◽

Middle Aged ◽

Aged Mice ◽

Future Fracture ◽

Systemic Bone Loss ◽

Young Mice

AbstractThe most reliable predictor of future fracture risk is a previous fracture of any kind. The etiology of this increased fracture risk is not fully known, but it is possible that fracture initiates systemic bone loss leading to greater fracture risk at all skeletal sites. In this study we investigated systemic bone loss and recovery following femoral fracture in young (3 month old) and middle-aged (12 month old) mice. Transverse femur fractures were created using a controlled impact, and whole-body bone mineral density (BMD), trabecular and cortical microstructure, bone mechanical properties, bone formation and resorption rates, mouse voluntary movement, and systemic inflammation were quantified at multiple time points post-fracture. We found that fracture led to decreased whole-body BMD in both young and middle-aged mice 2 weeks post-fracture; this bone loss was recovered by 6 weeks in young, but not middle-aged mice. Similarly, trabecular bone volume fraction (BV/TV) of the L5 vertebral body was significantly reduced in fractured mice relative to control mice 2 weeks post-fracture (−11% for young mice, −18% for middle-aged mice); this bone loss was fully recovered by 6 weeks post-fracture in young mice. At 3 days post-fracture we observed significant increases in serum levels of interleukin-6 and significant decreases in voluntary movement in fractured mice compared to control mice, with considerably greater changes in middle-aged mice than in young mice. At this time point we also observed increased osteoclast number on L5 vertebral body trabecular bone of fractured mice compared to control mice. These data show that systemic bone loss occurs after fracture in both young and middle-aged mice, and recovery from this bone loss may vary with age. This systemic response could contribute to increased future fracture risk following fracture, and these data may inform clinical treatment of fractures with respect to improving long-term skeletal health.

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