Intraperitoneal injection of Desferal® alleviated the age-related bone loss and senescence of bone marrow stromal cells in rats

Abstract Background Age-related bone loss plays a vital role in the development of osteoporosis and osteoporotic fracture. Bone marrow stromal cell (BMSC) senescence is highly associated with osteoporosis and limits the application of BMSCs in regenerative medicine. Hypoxia is an essential component for maintaining the normal physiology of BMSCs. We have reported that activation of hypoxia-induced factor by deletion of von Hippel-Lindau gene in osteochondral progenitor cells protected mice from aging-induced bone loss. However, whether pharmacologically manipulation of hypoxic niche would attenuate age-related bone loss and dysfunction of BMSCs is not well understood. Methods Twelve-month-old Sprague-Dawley rats were used as an aged model and were intraperitoneally injected with Desferal® (20, 60 mg/kg weight or vehicle), three times a week for a continuous 8-week period. Two-month-old young rats were set as a reference. After 8 weeks, micro-CT and HE staining were performed to determine the effect of Desferal® on bone loss. In order to investigate the effects of Desferal® on BMSC senescence, 12-month-old rats were treated with high-dose Desferal® (60 mg/kg weight) daily for 10 days. BMSCs were isolated and evaluated using CCK-8 assay, colony-forming cell assay, cell differentiation assay, laser confocal for reactive oxygen species (ROS) level, senescence-associated β-galactosidase (SA-β-gal) staining, and molecular expression test for stemness/senescence-associated genes. Results Micro-CT and HE staining showed that high-dose Desferal® significantly prevented bone loss in aged rats. Compared with vehicle group, the ex vivo experiments showed that short-term Desferal® administration could promote the potential of BMSC growth (proliferation and colony formation ability) and improve the rebalance of osteogenic and adipogenic differentiation, as well as rejuvenate senescent BMSCs (ROS level and SA-β-gal staining) and revise the expression of stemness/senescence-associated genes. The potential of BMSCs from 12M-H-Desferal® group at least partly revised to the level close to 2-month-old group. Conclusions The current study suggested that Desferal®, an iron-chelating agent, could alleviate age-related bone loss in middle-aged rats. Meanwhile, we found that short-term intraperitoneal injection of Desferal® partly rejuvenate BMSCs from aged rats. Overall, we demonstrated a novel role of Desferal® in rejuvenating aged BMSCs and preventing age-related bone loss.

Download Full-text

Short-term weekly chemotherapy followed by high-dose therapy with autologous bone marrow transplantation for lymphoblastic and Burkitt’s lymphomas in adult patients

Annals of Oncology ◽

10.1093/oxfordjournals.annonc.a059214 ◽

1995 ◽

Vol 6 (5) ◽

pp. 445-451 ◽

Cited By ~ 33

Author(s):

L.M. Jost ◽

E. Jacky ◽

C. Dommann-Scherrer ◽

H.-P. Honegger ◽

R. Maurer ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Transplantation ◽

Marrow Transplantation ◽

Autologous Bone Marrow Transplantation ◽

Autologous Bone Marrow ◽

High Dose ◽

High Dose Therapy ◽

Short Term ◽

Weekly Chemotherapy ◽

Autologous Bone

Download Full-text

A New Trabecular Region of Interest for Femoral Dual X-Ray Absorptiometry: Short-Term Precision, Age-Related Bone Loss, and Fracture Discrimination Compared with Current Femoral Regions of Interest

Journal of Bone and Mineral Research ◽

10.1359/jbmr.1997.12.5.832 ◽

1997 ◽

Vol 12 (5) ◽

pp. 832-838 ◽

Cited By ~ 7

Author(s):

Masahiko Takada ◽

Stephan Grampp ◽

Xiaolong Ouyang ◽

Klaus Engelke ◽

Harry K. Genant

Keyword(s):

Bone Loss ◽

Region Of Interest ◽

Regions Of Interest ◽

Short Term ◽

X Ray ◽

Age Related ◽

Fracture Discrimination

Download Full-text

Osteoanabolic effect of alendronate and zoledronate on bone marrow stromal cells (BMSCs) isolated from aged female osteoporotic patients and its implications for their mode of action in the treatment of age-related bone loss

Osteoporosis International ◽

10.1007/s00198-013-2494-3 ◽

2013 ◽

Vol 25 (3) ◽

pp. 1151-1161 ◽

Cited By ~ 22

Author(s):

R. A. Lindtner ◽

A. N. Tiaden ◽

K. Genelin ◽

H. L. Ebner ◽

C. Manzl ◽

...

Keyword(s):

Bone Marrow ◽

Bone Loss ◽

Stromal Cells ◽

Mode Of Action ◽

Bone Marrow Stromal Cells ◽

Marrow Stromal Cells ◽

Age Related

Download Full-text

Cycloastragenol prevents age-related bone loss: Evidence in d-galactose-treated and aged rats

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2020.110304 ◽

2020 ◽

Vol 128 ◽

pp. 110304

Author(s):

Yongjie Yu ◽

Jingkai Wu ◽

Jin Li ◽

Yanzhi Liu ◽

Xiaoyan Zheng ◽

...

Keyword(s):

Bone Loss ◽

Aged Rats ◽

Age Related

Download Full-text

3-Hydroxyanthranilic acid Administration Did Not Prevent Age Related Bone Loss

Innovation in Aging ◽

10.1093/geroni/igab046.2542 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 680-681

Author(s):

Carlos Isales ◽

Ke-Hong Ding ◽

Wendy Bollag ◽

Meghan McGee-Lawrence ◽

William Hill ◽

...

Keyword(s):

Bone Mineral Density ◽

Body Composition ◽

Bone Loss ◽

Bone Mineral ◽

Degradation Products ◽

High Dose ◽

Mineral Density ◽

Tryptophan Degradation ◽

Age Related ◽

Hydroxyanthranilic Acid

Abstract Aging is associated with accumulation of various tryptophan degradation products that may having either bone anabolic or catabolic effects. In epidemiologic studies, elevated levels of 3-hydroxyanthranilic acid (3-HAA) are associated with a higher bone mineral density (BMD). We have previously shown that the C57BL/6 mouse loses bone mass with age. Thus, we hypothesized that administering 3-HAA via a daily intraperitoneal (IP) injection would result in preserved or increased BMD. In an IACUC-approved protocol, we injected 26-month-old C57BL/6 mice with either a low dose (0.5 mg) or high dose (5 mg) of 3-HAA IP five days a week for eight weeks. At the end of this time mice were sacrificed and body composition and bone mineral density measured by DigiMus. BMD was significantly lower in the high dose 3-HAA group: 0.0570 + 0.004 vs 0.0473 + 0.006 vs 0.0432 + 0.0075 gm/cm2, (means+SD, Control vs 0.5 mg 3HAA vs 5 mg 3HAA, p=0.004, 0 vs 5.0 mg, n=6-9/group). 3-HAA had no significant impact on body composition (lean body mass: 86.7 + 1.7% vs 86.2 + 2.7% vs 86.1 + 2.0%, Control vs 0.5 mg vs 5.0 mg 3-HAA, p=ns; and fat mass 12.6 + 2.0% vs 13.8 + 2.7% vs 13.9 + 2.0% vs 0.2%, Control vs 0.5 vs 5 mg 3-HAA, p=ns). Thus, 3-HAA did not prevent bone loss in older mice but instead significantly worsened bone loss. 3-HAA is known to have both pro- and anti- oxidant effects depending on the environment. These data would suggest that at the higher concentrations 3-HAA is acting predominantly as a pro-oxidant molecule accelerating age-related bone loss.

Download Full-text

Effect of Short-Term, High-Dose Retinol on Dark Adaptation in Aging and Early Age-Related Maculopathy

Investigative Opthalmology & Visual Science ◽

10.1167/iovs.05-1292 ◽

2006 ◽

Vol 47 (4) ◽

pp. 1310 ◽

Cited By ~ 49

Author(s):

Cynthia Owsley ◽

Gerald McGwin ◽

Gregory R. Jackson ◽

Douglas C. Heimburger ◽

Chandrika J. Piyathilake ◽

...

Keyword(s):

Dark Adaptation ◽

Early Age ◽

High Dose ◽

Short Term ◽

Age Related

Download Full-text

Short-term Low-Dose mTORC1 Inhibition in Aged Rats Counter-Regulates Age-Related Gene Changes and Blocks Age-Related Kidney Pathology

The Journals of Gerontology Series A ◽

10.1093/gerona/glx249 ◽

2018 ◽

Vol 73 (7) ◽

pp. 845-852 ◽

Cited By ~ 26

Author(s):

Tea Shavlakadze ◽

Jiang Zhu ◽

Sharon Wang ◽

Weihua Zhou ◽

Bret Morin ◽

...

Keyword(s):

Low Dose ◽

Aged Rats ◽

Related Gene ◽

Short Term ◽

Kidney Pathology ◽

Age Related

Download Full-text

Bone Benefits of Fish Oil Supplementation Depend on its EPA and DHA Content

Nutrients ◽

10.3390/nu11112701 ◽

2019 ◽

Vol 11 (11) ◽

pp. 2701

Author(s):

Haissam Abou-Saleh ◽

Allal Ouhtit ◽

Ganesh V. Halade ◽

Md Mizanur Rahman

Keyword(s):

Bone Marrow ◽

Bone Resorption ◽

Bone Loss ◽

Fish Oil ◽

Signaling Pathways ◽

Dietary Intervention ◽

High Dose ◽

Chow Diet ◽

Bone Resorption Marker ◽

Mineral Density

The preventive effect of high-dose (9%) regular-fish oil (FO) against bone loss during aging has been demonstrated, but the effects of a low-dose (1%–4%) of a highly purified concentrated FO (CFO) has not been elucidated. The aim of this study was to determine the dose-dependent effect of a CFO against bone loss in C57BL/6 female mice during aging. Twelve-month old mice were fed with 1% and 4% CFO and 4% safflower oil (SFO) diets, including a group with a 4% regular-FO diet and a group with a lab chow diet for 12 months. Bone mineral density (BMD) was analyzed by dual-energy x-ray absorptiometry (DXA) before and after the dietary intervention. At the end of dietary intervention, bone resorption markers in serum and inflammatory markers in bone marrow and splenocytes and inflammatory signaling pathways in the bone marrow were analyzed. As compared to the 4% SFO control, 4% CFO maintained higher BMD during aging, while 1% CFO offered only a mild benefit. However, the 1% CFO fed group exhibited slightly better BMD than the 4% regular-FO fed group. BMD loss protection by CFO was accompanied by reduced levels of the bone resorption marker, TRAP, and the osteoclast-stimulating-factor, RANKL, without affecting the decoy-receptor of RANKL, osteoprotegerin (OPG). Further, CFO supplementation was associated with an increase in the production of IL-10, IL-12, and IFN-γ and a decrease in the production of TNF-α and IL-6, and the activation of NF-κB, p38 MAPK, and JNK signaling pathways. In conclusion, the supplementation of 4% CFO is very efficient in maintaining BMD during aging, whereas 1% CFO is only mildly beneficial. CFO supplementation starting at middle age may maintain better bone health during aging.

Download Full-text