scholarly journals CONTENT OF GROWTH FACTORS AND HYPOXIA-INDUCIBLE FACTOR IN THE SKIN OF RATS OF DIFFERENT AGE AFTER WOUND HEALING

2021 ◽  
Vol 67 (6) ◽  
pp. 40-45
Author(s):  
N.R. Hrytsevych ◽  
◽  
V.V. Vereschaka ◽  
L.І. Stepanova ◽  
N.S. Nikitina ◽  
...  
Keyword(s):  
Growth Factor ◽  
Abdominal Wall ◽  
Anterior Abdominal Wall ◽  
Hypoxia Inducible Factor ◽  
Complete Healing ◽  
Female Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Wound Surface ◽  
Young Rats ◽  
Old Rats

The aim of the study was to determine the content of vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and hypoxia-inducible factor-1alpha (HIF- 1α) in the skin of 40 female rats of different ages (3 and 12 mo) after closure of the wound bed. In each age group composed of 20 rats, 10 rats served as a control group, and in remaining rats a facelift operation was performed and cut wounds on the anterior abdominal wall (5 cm × 0.5 cm) were simulated. The duration of wound surface healing in rats of different age groups was recorded. On the day of complete healing, the animals were killed, and the skin was cut in the areas of the former wound bed. In control rats, the skin was excised in the same places. The content of VEGF, NGF and HIF-1α was determined in the skin by enzyme- linked immunosorbent assay. It was found that in the group of young (3-month-old) rats, complete healing of the wound surface after facelift surgery occurred after 14.0 ± 1.0 days, and on the anterior abdominal wall - after 13.0 ± 1.0 days. In 12-month-old rats, the duration of wound surface healing after facelift surgery and incised wound on the anterior abdominal wall increased to 17.0 ± 1.5 days. In the former wound bed, the content of HIF-1α in young rats increased by 60.7%, and in 12-month-old rats - by 231.6%. In the former wound bed, the content of VEGF and NGF in young rats increased by 14.8 and 11.7%, respectively, and in 12-month-old rats - by 182.4 and 152.6%, respectively. It was concluded that more pronounced hypoxia in the skin after surgery in 12-month-old rats may be the cause of postoperative complications.

EFFECTS OF AGE AND OVARIAN FUNCTION ON THE PITUITARY–THYROID SYSTEM IN FEMALE RATS

1978 ◽  
Vol 78 (2) ◽  
pp. 225-232 ◽  
Author(s):  
H. J. CHEN ◽  
P. G. WALFISH
Keyword(s):  
Ovarian Function ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Lower Percentage ◽  
Female Rat ◽  
Thyrotrophin Releasing Hormone ◽  
Young Rats ◽  
Trh Stimulation ◽  
Old Rats ◽  
Absolute Concentrations

SUMMARY The effects of ovariectomy and ovariectomy and treatment with oestradiol benzoate (OB) on the basal concentration of thyrotrophin (TSH), the total concentrations and concentrations of free tri-iodothyronine (T3) and thyroxine (T4), and the concentrations of TSH, T3 and T4 observed after treatment with thyrotrophin releasing hormone (TRH) were studied in old (16–17 months of age) constant oestrous and young (3–4 months of age) oestrous rats. The untreated old control rats had significantly (P< 0·001) lower basal total T4 concentrations and percentage and absolute concentrations of free T4 and lower percentage and absolute concentrations of free T3 than untreated young rats. The basal levels of TSH in these two groups were similar and the increases in TSH after injection of TRH were identical. Two weeks after ovariectomy, no significant additional differences in hormone concentrations between old and young rats were observed. However, release of TSH induced by TRH was increased by three- to fourfold in old rats after ovariectomy compared with nine- to tenfold in young ovariectomized rats (P<0·01). Basal T4 concentrations remained unchanged in old ovariectomized rats treated for 7 days with 2 μg OB/day compared with both intact and ovariectomized rats. However, T4 concentrations in OB-treated young rats were significantly (P<0·001) reduced. Treatment with OB significantly increased both basal and TRH-induced T3 and TSH levels in old and young rats although the young rats showed a greater response (P<0·001). Two hours after injection of TRH, serum T3 concentrations in old rats increased only after OB treatment and not after ovariectomy alone or in intact rats, whereas T3 concentrations rose in all three groups of young animals. These results indicate that (1) older female rats have lower total T4, free T4 and free T3 concentrations and a lower TSH response to TRH, (2) OB treatment in young rats suppresses serum T4 but increases serum T3 and results in a greater TSH response to TRH and (3) at least one of the mechanisms accounting for the alterations in thyroid function observed in the older female rat, in addition to possible concomitant primary thyroid gland hypofunction, is a hyporesponsiveness of pituitary thyrotrophs to both endogenous negative feedback signals from low serum thyroid hormone concentrations and exogenous TRH stimulation.

Age-related alterations in prolactin binding sites in the female rat

1991 ◽  
Vol 124 (3) ◽  
pp. 314-321 ◽  
Author(s):  
Philippe Schneiter ◽  
Marianne J. Reymond ◽  
Thérèse Lemarchand-Béraud
Keyword(s):  
Binding Sites ◽  
Mammary Glands ◽  
Female Rats ◽  
Affinity Constant ◽  
Female Rat ◽  
Binding Studies ◽  
Young Rats ◽  
Age Related ◽  
Old Rats ◽  
Nulliparous Female

Abstract. Aging is associated with various neuroendocrine alterations, including in the rat a hypersecretion of PRL with maintained ovulations (repetitive pseudopregnancy) and a reduced activity of the hypothalamic dopaminergic neurons with loss of the neuron responsiveness to PRL, suggestive of age-related alterations in PRL receptors. In this study we have investigated PRL binding sites in the hypothalamus as well as in the mammary glands, the ovaries and the liver of young and old nulliparous female rats. The old rats (26-28 months) displayed spontaneous repetitive pseudopregnancies and they were compared with young (4-6 months) pseudopregnant rats; the binding studies were performed by saturation analysis using 125I-oPRL as ligand and particulate membrane preparations. In the hypothalamus, a negligible binding of PRL was observed in all fragments studied, mediobasal hypothalamus, median eminence, in both young and old rats and no characterization of the binding sites could be achieved. In the mammary glands, the number of PRL binding sites was appreciable in spite of the nulliparity of the rats, but it was smaller in the old than in the young rats (9.0±1.4 vs 14.9±1.2 fmol/mg protein; mean ± sem; p<0.02). In the ovaries, the density of PRL binding sites was similar in the old and young rats (112.6±9.7 vs 115.0±8.9 fmol/mg protein), illustrative of a maintained luteotropic effect of PRL with age in the rat. In contrast, in the liver a greater number of binding sites was found in the old than in the young rats (261.9±36.6 vs 63.6±5.8 fmol/mg protein; p<0.001), supportive of the ability of PRL to induce its own receptors in that tissue. The affinity constant of PRL binding was not altered with age in the tissues studied. These results are illustrative of tissue-specific modifications in the number of PRL binding sites with age and they are suggestive of a sustained biological activity of PRL in the old rats.

scholarly journals Age impairs Flk-1 signaling and NO-mediated vasodilation in coronary arterioles

2008 ◽  
Vol 295 (6) ◽  
pp. H2280-H2288 ◽  
Author(s):  
Amanda J. LeBlanc ◽  
Robert D. Shipley ◽  
Lori S. Kang ◽  
Judy M. Muller-Delp
Keyword(s):  
Nitric Oxide ◽  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Coronary Resistance ◽  
Young Rats ◽  
Age Related ◽  
Old Rats ◽  
Endothelial Growth Factor ◽  
Coronary Arterioles

Impairment of flow-induced vasodilation in coronary resistance arterioles may contribute to the decline in coronary vasodilatory reserve that occurs with advancing age. This study investigated the effects of age on flow-induced signaling and activation of nitric oxide (NO)-mediated vasodilation in coronary resistance arterioles. Coronary arterioles were isolated from young (∼6 mo) and old (∼24 mo) male Fischer-344 rats to assess vasodilation to flow, vascular endothelial growth factor (VEGF), and ACh. Flow- and VEGF-induced vasodilation of coronary arterioles was impaired with age ( P ≤ 0.05); however, ACh-induced vasodilation was preserved with age. NG-nitro-l-arginine methyl ester (l-NAME) (1 × 10−5 M) eliminated vasodilation to flow, VEGF, and ACh, indicating dependence of these responses on NO. SU-1498, an inhibitor of vascular endothelial growth factor receptor 2 (VEGFR, also known as Flk-1), abolished age-related differences in flow-induced vasodilation. Flow-stimulated phosphorylation of Flk-1 in coronary arterioles from young but not old rats and Flk-1 protein was reduced in coronary arterioles from old rats compared with those from young rats. Flow stimulated phosphorylation of endothelial nitric oxide synthase (eNOS) in coronary arterioles from both young and old rats. VEGF induced phosphorylation of both protein kinase B (Akt) and eNOS in coronary arterioles. VEGF-induced phosphorylation of Akt, but not eNOS, was significantly reduced in arterioles from old rats compared with arterioles from young rats. Wortmannin, an inhibitor of phosphatidylinositol (PI) 3-kinase, eliminated age-related differences in both flow- and VEGF-induced vasodilation. These results indicate that impairment of Flk-1/PI3-kinase signaling contributes to the reduction of flow-induced vasodilation in coronary arterioles with advancing age.

Age-related differences in basal and calcium-stimulated plasma calcitonin levels in female rats

1992 ◽  
Vol 262 (5) ◽  
pp. E557-E560
Author(s):  
C. L. Tsai ◽  
H. F. Pu ◽  
C. P. Lau ◽  
P. S. Wang ◽  
T. K. Liu
Keyword(s):  
Ovarian Function ◽  
Estradiol Benzoate ◽  
Young Female ◽  
Female Rats ◽  
Target Tissue ◽  
Young Rats ◽  
Ovx Rats ◽  
Age Related ◽  
Old Rats ◽  
Effects Of Aging

The effects of aging on calcitonin (CT) secretion in female rats were investigated. Old (24 mo) at constant diestrus status and young (2 mo) at diestrus status rats were either ovariectomized (Ovx) or left intact as controls. Ovx rats were injected subcutaneously with estradiol benzoate (25 micrograms/kg body wt) or sesame oil one time per day for 3 days. All rats were infused with CaCl2 (10 mg/ml) at a rate of 2 ml/h for 30 min via a jugular catheter connected to a peristaltic pump. Blood samples (0.5 ml each) were collected at 0, 30, 60, and 120 min. The basal and post-CaCl2 levels of plasma Ca measured with radioimmunoassay were significantly higher (P less than 0.05-0.01) in old than in young female rats. The pre- and post-CaCl2 levels of plasma Ca and CT in young rats were not altered by Ovx or estradiol replacement. In old rats, Ovx caused a higher (P less than 0.01) level in plasma CT at 0 and 30 min after CaCl2 infusion. Both basal and stimulated levels of plasma CT were higher (P less than 0.01) in old Ovx than in young Ovx rats. These results demonstrated that 1) the increase of plasma CT in response to Ca challenge was greater in old than in young female rats, 2) the influence of estradiol and ovarian function on plasma CT concentration increases as a function of age, and 3) estradiol reduced the plasma CT in response to hypercalcemia in old Ovx rats. The sensitivity of the target tissue of young rats may be lower in response to the modulation of estrogen during hypercalcemia without compromising the secretion and hypocalcemic effect of CT in young rats. All suggested an age-related relationship between estrogen and CT secretion in minute-to-minute regulation during Ca infusion in rats.

Association of insulin-like growth factor mRNA expressions with muscle regeneration in young, adult, and old rats

1997 ◽  
Vol 273 (1) ◽  
pp. R353-R358 ◽  
Author(s):  
D. R. Marsh ◽  
D. S. Criswell ◽  
M. T. Hamilton ◽  
F. W. Booth
Keyword(s):  
Young Adult ◽  
Growth Factor ◽  
Mrna Expression ◽  
Tibialis Anterior ◽  
Tibialis Anterior Muscle ◽  
Insulin Like Growth Factor ◽  
Adult Rats ◽  
Young Rats ◽  
Igf I ◽  
Old Rats

The purpose of this study was to determine whether impaired regeneration of skeletal muscle in old rats can be attributed to diminished expression of insulin-like growth factor (IGF) mRNAs. Fischer 344 male rats aged 2 (young), 12 (adult), and 24 mo (old) were given an injection of the myotoxic anesthetic, bupivacaine, into the left tibialis anterior muscle. Muscle mass and protein concentration recovered to contralateral control values by 28 days in young, but not adult or old rats. The temporal and maximal expressions of IGF-I mRNA were similar during recovery from bupivacaine on days 5 and 10 in young, adult, and old rat muscles. IGF-I mRNA levels were reduced toward control levels in young rats by 15 days, but remained elevated in adult and old rats. IGF-I receptor mRNA in bupivacaine-injected muscle of old rats was elevated significantly higher than injected muscle of young and adult rats at recovery day 5. Five days after bupivacaine injection, IGF-II mRNA was increased 46-fold in young rats but was only increased fourfold in adult rats. Thereafter, IGF-II mRNA expression was similar for young, adult, and old rats at 10 and 15 days of recovery. In summary, we demonstrate that impaired regeneration of the tibialis anterior muscle in adult or old rats after bupivacaine-induced damage is associated with a prolonged elevation of IGF-I mRNA expression and/or diminished initial IGF-II mRNA expression.

scholarly journals Levels of Serum 25(OH)VD3, HIF-1α, VEGF, vWf, and IGF-1 and Their Correlation in Type 2 Diabetes Patients with Different Urine Albumin Creatinine Ratio

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Ying Shao ◽  
Chuan Lv ◽  
Qin Yuan ◽  
Qiuyue Wang
Keyword(s):  
Type 2 Diabetes ◽  
Growth Factor ◽  
Hypoxia Inducible Factor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Vascular Endothelial ◽  
Protective Effects ◽  
Serum Factors ◽  
Diabetes Patients

Objective.To investigate changes in serum 25(OH)VD3, HIF-1α, VEGF, vWf, IGF-1, and their correlation in type 2 diabetes patients at different stages of diabetic kidney disease (DKD).Methods.502 type 2 diabetes patients were divided into three groups: Normoalbuminuric group (201 patients), Microalbuminuric group (171 patients), and Macroalbuminuric group (130 patients). Serum 25-hydroxyvitamin D3[25(OH)VD3] was measured by chemiluminescence. Serum hypoxia-inducible factor-1α(HIF-1α), vascular endothelial growth factor (VEGF), von Willebrand factor (vWf), and insulin-like growth factor-1 (IGF-1) were determined by enzyme-linked immunosorbent assay. We detected the aforementioned serum factors in all cases and 224 control subjects.Results.Serum HIF-1α, VEGF, vWf, and IGF-1 in type 2 diabetes patients were significantly higher than those in the control group and increased with the increase of Ln(ACR), respectively (P<0.001). Serum 25(OH)VD3was significantly lower in type 2 diabetes patients and decreased with the increase of Ln(ACR) (P<0.001). Ln(ACR) was positively correlated with duration, HbA1c, Scr, BUN, TC, LDL, TG, UA, HIF-1α, VEGF, IGF-1, vWf, and Fg and negatively correlated with 25(OH)VD3and eGFR.Conclusion. Serum HIF-1α, VEGF, vWf, and IGF-1 may be involved in DKD process through inflammation, angiogenesis, and endothelial injury. Serum 25(OH)VD3may have protective effects on DKD partly by inhibiting inflammation, abnormal angiogenesis, and vascular endothelial dysfunction.

Expression of hypoxia inducible factor—1 alpha and correlation with preoperative embolization of meningiomas

2002 ◽  
Vol 97 (3) ◽  
pp. 658-667 ◽  
Author(s):  
Randy L. Jensen ◽  
Scott Soleau ◽  
Mihir K. Bhayani ◽  
Dustin Christiansen
Keyword(s):  
Growth Factor ◽  
Cell Cultures ◽  
Strong Correlation ◽  
Cultured Cells ◽  
Hypoxia Inducible Factor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Preoperative Embolization ◽  
Content Type ◽  
Meningioma Cell ◽  
Fine Print

Object. Vascular endothelial growth factor (VEGF) has been implicated in meningioma tumorigenesis and growth. The production of VEGF is regulated by hypoxia inducible factor—1α (HIF-1α), especially under conditions of hypoxia. In this study, the authors examine the expression of HIF-1α and VEGF in meningiomas, with a special emphasis on conditions of hypoxia, such as preoperative embolization, and on in vitro studies in cultured cells. Methods. Meningiomas obtained in 142 patients were studied using immunohistochemical methods to detect HIF-1α and the results were correlated with the extent or lack of preoperative embolization and expression of VEGF. Primary meningioma cell cultures were established and cell culture experiments were performed using a hypoxia chamber to stimulate HIF-1α and VEGF production. Expression of HIF-1α in primary meningioma cell cultures was measured using immunoblot assays. The VEGF secretion was measured using enzyme-linked immunosorbent assay. Half of the meningiomas studied were positive for HIF-1α, with a strong correlation between complete embolization and HIF-1α expression. Most of the meningiomas studied expressed VEGF protein, and VEGF expression did not correlate with the degree of embolization. A strong correlation was found between VEGF and HIF-1α expression in immunohistochemical studies. Secretion of VEGF is increased by hypoxia and growth factor stimulation. In meningiomas, growth factors stimulate HIF-1α expression. The role of hypoxia is less clear. Conclusions. The expression of HIF-1α is increased by complete preoperative embolization of meningiomas. The expression of HIF-1α also correlates with VEGF secretion in meningiomas. Growth factor and hypoxic stimulation both contribute to VEGF control, but which is most important (or whether both are equally important) will require further studies.

Growth factor-mediated reversal of senescent dysfunction of ischemia-induced cardioprotection

2006 ◽  
Vol 290 (2) ◽  
pp. H525-H530 ◽  
Author(s):  
Jingang Zheng ◽  
Andrew Chin ◽  
Inga Duignan ◽  
Kyung-Heon Won ◽  
Mun K. Hong ◽  
...  
Keyword(s):  
Growth Factor ◽  
Left Ventricular ◽  
Postmyocardial Infarction ◽  
Young Rats ◽  
Tnf Α ◽  
Old Rats ◽  
Factor Α ◽  
Angiopoietin 2 ◽  
Endothelial Growth Factor ◽  
Fractional Shortening

Based on the role of tumor necrosis factor-α (TNF-α) in ischemic preconditioning (IPC) and the age-associated loss of both TNF-α-induced platelet-derived growth factor-AB (PDGF-AB)-mediated cardioprotection and IPC-mediated cardioprotection, we hypothesized that targeting of PDGF-AB-based pathways would restore cardioprotection by IPC in the aging heart. To study this, IPC was induced in 4- and 24-mo-old F344 rats. Sections of young hearts isolated 1 day post-IPC revealed increased TNF-α compared with controls. In old rats, TNF-α was higher at baseline than IPC young rats and was not significantly altered after IPC. Treatment of old rats with PDGF-AB with vascular endothelial growth factor and angiopoietin-2 (a combination termed PVA), but not PDGF-AB alone, at the time of IPC decreased TNF-α. In addition, when compared with young hearts, IPC induced greater apoptosis in the old hearts, which was decreased with PVA treatment but was markedly increased with PDGF-AB. To test the significance of these findings, additional rats underwent permanent coronary ligation 1 day post-IPC. IPC was cardioprotective in young rats [14 days postmyocardial infarction (MI), fractional shortening 29 ± 6% vs. control MI 17 ± 4%, P < 0.05; Masson’s trichrome stain MI size: 13 ± 2% vs. control MI 17 ± 4% left ventricular area (LVA); P < 0.05]. In old rats, however, IPC reduced the post-MI 14-day survival (33% vs. controls 67%; P < 0.05). Treatment of IPC-aging rats with PVA, but not PDGF-AB-alone, reversed IPC-induced mortality (PVA-IPC-MI survival, 88%; PDGF-AB-IPC-MI, 14%) and reduced myocardial injury (fractional shortening: PVA-IPC, 31 ± 1% vs. control MI, 21 ± 6%, P < 0.05; MI size: PVA-IPC, 12 ± 2% vs. control MI, 18 ± 3% LVA, P < 0.05) and thus demonstrated that PDGF-AB-based pathways can reverse the senescent impairment in IPC-mediated cardioprotection.

scholarly journals Increasing transforming growth factor-beta concentrations with age decrease apelin in the rat rotator cuff

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ryo Tazawa ◽  
Kentaro Uchida ◽  
Tomonori Kenmoku ◽  
Mitsufumi Nakawaki ◽  
Kyoko Muneshige ◽  
...  
Keyword(s):  
Growth Factor ◽  
Rotator Cuff ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Mrna Levels ◽  
Rt Pcr ◽  
Young Rats ◽  
Β Protein ◽  
Growth Factor Beta

Abstract Background The rotator cuff undergoes natural degeneration with age, leading to age-related rotator cuff tear; however, the precise mechanism remains unclear. Transforming growth factor-beta (TGF-β) concentrations rise with age and TGF-β contributes to the pathophysiology of skeletal muscle. TGF-β has also been shown to suppress expression of the myokine, apelin, in skin fibroblasts. We hypothesized that TGF-β expression in the rotator cuff changes with age and regulates apelin expression, thereby contributing to rotator cuff degeneration. Methods We used quantitative reverse-transcription polymerase chain reaction (Q-RT-PCR) to measure the expression of apelin and tendon-related genes (Tnmd, Col1a1, and Col3a1) in the rotator cuff of young (12 weeks), adult (24 weeks), and old (48 weeks) rats. Using Q-RT-PCR and enzyme-linked immunosorbent assay, we also measured Tgfb mRNA and TGF-β protein levels, respectively. Furthermore, we used Q-RT-PCR to measure apelin mRNA levels in rotator cuff-derived cells after treatment with 0 (control) and 10 ng/mL recombinant TGF-β. Results Apelin mRNA levels were significantly lower in old compared to young and adult rats. Similarly, tendon-related genes, Tnmd, Col1a1, and Col3a1, were significantly lower in adult and old rats than young rats. In contrast, Tgfb mRNA and TGF-β protein were significantly higher in old compared to young rats. Stimulation with exogenous TGF-β significantly decreased Apelin mRNA expression compared to control. Conclusions TGF-β regulates apelin expression in the rotator cuff and may play a key role in the degenerative pathology of the rotator cuff with age.

Aging alters the skeletal response to disuse in the rat

2007 ◽  
Vol 292 (2) ◽  
pp. R988-R996 ◽  
Author(s):  
Daniel S. Perrien ◽  
Nisreen S. Akel ◽  
Esther E. Dupont-Versteegden ◽  
Robert A. Skinner ◽  
Eric R. Siegel ◽  
...  
Keyword(s):  
Growth Factor ◽  
Bone Morphogenetic Protein ◽  
Osteogenic Potential ◽  
Insulin Like Growth Factor ◽  
Factor I ◽  
Young Rats ◽  
Morphogenetic Protein ◽  
Old Rats ◽  
Skeletal Effects ◽  
Growth Factor I

Disuse has been shown to cause a rapid and dramatic loss of skeletal mass and strength in the load-bearing 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-γ-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.

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