Dissociation of Bone Mineral Density From Age-related Decreases in Insulin-like Growth Factor-I and Its Binding Proteins in the Male Rat

Benedict, Mark R.; Adiyaman, Sinan; Ayers, David C.; Thomas, F. D.; Calore, James D.; Dhar, V.; Richman, Robert A.

doi:10.1093/geronj/49.5.b224

Cited by 19 publications

(10 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Male Fischer 344/Brown Norway rats (6 and 32 mo of age) were purchased from the National Institute on Aging. This strain of rat has increased longevity and decreased cumulative lesion incidence compared with other strains; therefore, aging aspects can be studied in the relative absence of disease (4,38,65). The different ages were chosen to reflect a mature rat (6 mo) and an old rat at ϳ50% mortality (32 mo).…”

Section: Methodsmentioning

confidence: 99%

“…Age-related decreases in serum IGF-I have been described in humans (for review see Ref. 73) and in rats (4), and the circulating levels of IGF-I have been shown to directly regulate bone growth and density (68). Thus we investigated whether IGF-I levels were also sensitive to HS in young and old rats.…”

Section: Hs Reduces the Pool Of Committed Adipocyte Precursors But Nmentioning

confidence: 99%

See 1 more Smart Citation

Aging alters the skeletal response to disuse in the rat

Perrien¹,

Akel²,

Dupont‐Versteegden³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Perrien DS, Akel NS, Dupont-Versteegden EE, Skinner RA, Siegel ER, Suva LJ, Gaddy D. Aging alters the skeletal response to disuse in the rat. Am J Physiol Regul Integr Comp Physiol 292: R988 -R996, 2007. First published October 26, 2006; doi:10.1152/ajpregu.00302.2006.-Disuse has been shown to cause a rapid and dramatic loss of skeletal mass and strength in the loadbearing bones of young and mature animals and humans. However, little is known about the skeletal effects of disuse in aged mammals. The present study was designed to determine whether the skeletal effects of disuse are maintained with extreme age. Fischer 344/Brown Norway male rats (6 and 32 mo old) were hindlimb suspended (HS) or housed individually for 2 wk. Trabecular volume and microarchitecture in the proximal tibia were significantly decreased by HS only in young rats. HS significantly reduced cortical bone mineral density and increased cortical porosity only in old rats by inducing new pore formation. Cortical pore diameter was also increased in old rats, regardless of loading condition. Ex vivo osteogenic and adipogenic cultures established from each group demonstrated that age and HS decreased osteoblastogenesis. Age, but not HS, decreased sensitivity to endogenous bone morphogenetic protein stimulation, as measured by treatment with exogenous Noggin. Adipocyte development increased with age, whereas HS suppressed sensitivity to peroxisome proliferator-activated receptor-␥-induced differentiation. Serum insulin-like growth factor I levels were reduced with HS in young rats and with age in control and HS rats. These results suggest that the site of bone loss due to disuse is altered with age and that the loss of osteogenic potential with disuse in the old rats may be due to the combined effects of decreased insulin-like growth factor I levels and sensitivity, as well as diminished bone morphogenetic protein production. hindlimb suspension; osteopenia; osteoblast; bone morphogenetic protein; insulin-like growth factor I AGING IS ASSOCIATED WITH FUNCTIONAL changes in many tissues, such as a decline in muscle mass and strength and reduced bone density (8,16,30,38,42,59). With aging, bone and muscle mass regress in a parallel fashion (51). The osteopenia has far-reaching consequences on the ability of the elderly to perform tasks of daily living and to be functionally independent. Indeed, one of the major concerns of aging is the loss of bone mass and strength, which is associated with an increased risk of fractures (1,9,18,51). Moreover, the elderly are often subjected to periods of inactivity, such as bed rest, due to diseases or surgeries. The association of inactivity with decreases in muscle mass and bone density in young people and animals is well documented, and the mechanisms responsible for these losses have been the subject of intense investigation (2,20,23,39,40,49,51).Recent evidence suggests that the increased bone fragility that occurs with aging is multifactorial: decreased bone mineral density (BMD), as well as changes in bone m...

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Hs Reduces the Pool Of Committed Adipocyte Precursors But Nmentioning

confidence: 99%

Aging alters the skeletal response to disuse in the rat

Perrien¹,

Akel²,

Dupont‐Versteegden³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…Studies in old rats have shown that the local expression of IGF‐I mRNA in bone declines with age (11) . The content of IGF‐I is lower in old bone as compared with young bone (12) . In addition, the effective dose of IGF‐I required to stimulate DNA synthesis is shifted two orders of magnitude higher for old osteoprogenitor cells (13) .…”

Section: Introductionmentioning

confidence: 99%

Effect of Locally Infused IGF-I on Femoral Gene Expression and Bone Turnover Activity in Old Rats

Wakisaka

Tanaka

Barnes

et al. 1998

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Previously, we showed that the age-dependent deficit in bone formation activity can be attributed in part to a decline in local expression of insulin-like growth factor I (IGF-I) and altered mitogenic response of old osteoprogenitor cells to IGF-I. To establish the cellular basis for using IGF-I as a possible therapeutic agent for osteoporosis, we examined the effect of locally infused (50 ng/day for 14 days) on the expression of osteoblastrelated genes in femurs of old rats. Northern and dot blot analyses showed that the expression of procollagen (I), osteopontin, alkaline phosphatase, and osteocalcin was increased 0.4-to 1.5-fold in IGF-1-treated femurs as compared with control femurs. Histomorphometric analyses were carried out in parallel experiments to assess the changes in bone remodeling activity. Trabecular bone volume, trabecular number, and trabecular thickness were increased 56%, 29%, and 23%, respectively, whereas trabecular separation was reduced 26% by IGF-1 treatment. IGF-I treatment increased significantly the osteoid volume, osteoid surface, osteoblast number, and osteoblast surface. Mineralizing surface and mineral apposition rate, kinetic indices of bone formation, were also stimulated by IGF-I treatment. The bone formation rate was stimulated 81% in IGF-I-treated femurs as compared with control femurs. In contrast, eroded surface and osteoclast surface, parameters associated with bone resorption, were not affected by IGF-I treatment. These findings suggest that local administration of IGF-I into femurs of old rats can stimulate the expression of matrix proteins and improve trabecular bone status by stimulating bone formation without any appreciable effect on bone resorption. (J Bone Miner Res 1998;13:13-19)

show abstract

“…The use of human bmMSCs in this study was approved by the Institutional Review Board of Miaoli General Hospital. Isolation of bmMSCs from marrow aspirates was performed as described previously 28. Cells were cultured in Dulbecco's modified Eagle's medium (DMEM) (low glucose) (GIBCO-BRL) containing fetal bovine serum (15%) (Hyclone), glutamine, penicillin and streptomycin (GIBCO-BRL), and maintained in a humidified atmosphere containing 5% CO 2 at 37℃.…”

Section: Methodsmentioning

confidence: 99%

“…A causative role that the compromised IGF-1 signaling plays in the aging-related decrease of bmMSCs' osteogenic capability and bone deficit is suggested by several informative findings 26, 27. In experimental animals, it was found that the content of IGF-1 and the local expression of IGF-1 in bone decreased with aging 28-30. It has also been shown that while IGF-1 could consistently activate genes that are related to osteogenic function, the mitogenic activity of IGF-1 was impaired in aged rats 24.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Insulin-Like Growth Factor 1 Enhanced the Osteogenic Capability of Aging Bone Marrow Mesenchymal Stem Cells

et al. 2017

View full text Add to dashboard Cite

Many studies have indicated that loss of the osteoblastogenic potential in bone marrow mesenchymal stem cells (bmMSCs) is the major component in the etiology of the aging-related bone deficit. But how the bmMSCs lose osteogenic capability in aging is unclear. Using 2-dimentional cultures, we examined the dose response of human bmMSCs, isolated from adult and aged donors, to exogenous insulin-like growth factor 1 (IGF-1), a growth factor regulating bone formation. The data showed that the mitogenic activity and the osteoblastogenic potential of bmMSCs in response to IGF-1 were impaired with aging, whereas higher doses of IGF-1 increased the proliferation rate and osteogenic potential of aging bmMSCs. Subsequently, we seeded IGF-1-overexpressing aging bmMSCs into calcium-alginate scaffolds and incubated in a bioreactor with constant perfusion for varying time periods to examine the effect of IGF-1 overexpression to the bone-forming capability of aging bmMSCs. We found that IGF-1 overexpression in aging bmMSCs facilitated the formation of cell clusters in scaffolds, increased the cell survival inside the cell clusters, induced the expression of osteoblast markers, and enhanced the biomineralization of cell clusters. These results indicated that IGF-1 overexpression enhanced cells' osteogenic capability. Thus, our data suggest that the aging-related loss of osteogenic potential in bmMSCs can be attributed in part to the impairment in bmMSCs' IGF-1 signaling, and support possible application of IGF-1-overexpressing autologous bmMSCs in repairing bone defect of the elderly and in producing bone graft materials for repairing large scale bone injury in the elderly.

show abstract

Dissociation of Bone Mineral Density From Age-related Decreases in Insulin-like Growth Factor-I and Its Binding Proteins in the Male Rat

Cited by 19 publications

References 0 publications

Aging alters the skeletal response to disuse in the rat

Aging alters the skeletal response to disuse in the rat

Effect of Locally Infused IGF-I on Femoral Gene Expression and Bone Turnover Activity in Old Rats

Overexpression of Insulin-Like Growth Factor 1 Enhanced the Osteogenic Capability of Aging Bone Marrow Mesenchymal Stem Cells

Contact Info

Product

Resources

About