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International Journal of Molecular... Jun 2023Irisin is a peptide secreted by skeletal muscle that plays a major role in bone metabolism. Experiments in mouse models have shown that administration of recombinant...
Irisin is a peptide secreted by skeletal muscle that plays a major role in bone metabolism. Experiments in mouse models have shown that administration of recombinant irisin prevents disuse-induced bone loss. In this study, we aimed to evaluate the effects of irisin treatment for the prevention of bone loss in the ovariectomized (Ovx) mouse, the animal model commonly used to investigate osteoporosis caused by estrogen deficiency. Micro-Ct analysis conducted on Sham mice (Sham-veh) and Ovx mice treated with vehicle (Ovx-veh) or recombinant irisin (Ovx-irisn) showed bone volume fraction (BV/TV) decreases in femurs (Ovx-veh 1.39± 0.71 vs. Sham-veh 2.84 ± 1.23; = 0.02) and tibia at both proximal condyles (Ovx-veh 1.97 ± 0.68 vs. Sham-veh 3.48 ± 1.26; = 0.03) and the subchondral plate (Ovx-veh 6.33 ± 0.36 vs. Sham-veh 8.18 ± 0.41; = 0.01), which were prevented by treatment with a weekly dose of irisin for 4 weeks. Moreover, histological analysis of trabecular bone showed that irisin increased the number of active osteoblasts per bone perimeter (Ovx-irisin 32.3 ± 3.9 vs. Ovx-veh 23.5 ± 3.6; = 0.01), while decreasing osteoclasts (Ovx-irisin 7.6 ± 2.4 vs. Ovx-veh 12.9 ± 3.04; = 0.05). The possible mechanism by which irisin enhances osteoblast activity in Ovx mice is upregulation of the transcription factor , one of the key markers of osteoblast differentiation, and osteoprotegerin, thereby inhibiting osteoclast formation.
Topics: Mice; Animals; Female; Humans; Fibronectins; Cancellous Bone; Osteoporosis; Bone Diseases, Metabolic; Disease Models, Animal; Osteoblasts; Ovariectomy; Bone Density
PubMed: 37373043
DOI: 10.3390/ijms24129896 -
Journal of Women's Health (2002) Jul 2023Hysterectomy, oophorectomy, and tubal ligation are common surgical procedures. The literature regarding cardiovascular disease (CVD) risk after these surgeries has...
Hysterectomy, oophorectomy, and tubal ligation are common surgical procedures. The literature regarding cardiovascular disease (CVD) risk after these surgeries has focused on oophorectomy with limited research on hysterectomy or tubal ligation. Participants in the Nurses' Health Study II ( = 116,429) were followed from 1989 to 2017. Self-reported gynecologic surgery was categorized as follows: no surgery, hysterectomy alone, hysterectomy with unilateral oophorectomy, and hysterectomy with bilateral oophorectomy. We separately investigated tubal ligation alone. The primary outcome was CVD based on medical-record confirmed fatal and nonfatal myocardial infarction, fatal coronary heart disease, or fatal and nonfatal stroke. Our secondary outcome expanded CVD to include coronary revascularization (coronary artery bypass graft surgery, angioplasty, stent placement). Cox proportional hazard models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) and were adjusted for confounding factors. We investigated differences by age at surgery (≤50, >50) and menopausal hormone therapy usage. At baseline, participants were on average, 34 years old. During 2,899,787 person-years, we observed 1,864 cases of CVD. Hysterectomy in combination with any oophorectomy was associated with a greater risk of CVD in multivariable-adjusted models (HR hysterectomy with unilateral oophorectomy:1.40 [95% CI: 1.08-1.82]; HR hysterectomy with bilateral oophorectomy:1.27 [1.07-1.51]). Hysterectomy alone, hysterectomy with oophorectomy, and tubal ligation were also associated with an increased risk of combined CVD and coronary revascularization (HR hysterectomy alone: 1.19 [95% CI: 1.02-1.39]; HR hysterectomy with unilateral oophorectomy: 1.29 [1.01-1.64]; HR hysterectomy with bilateral oophorectomy: 1.22 [1.04-1.43]; HR tubal ligation: 1.16 [1.06-1.28]). The association between hysterectomy/oophorectomy and CVD and coronary revascularization risk varied by age at gynecologic surgery, with the strongest association among women who had surgery before age 50 years. Our findings suggest that hysterectomy, alone or in combination with oophorectomy, as well as tubal ligation, may be associated with an increased risk of CVD and coronary revascularization. These findings extend previous research finding that oophorectomy is associated with CVD.
Topics: Female; Humans; Middle Aged; Adult; Cardiovascular Diseases; Sterilization, Tubal; Risk Factors; Ovariectomy; Hysterectomy; Nurses
PubMed: 37155739
DOI: 10.1089/jwh.2022.0207 -
Obstetrics and Gynecology Mar 2020
Topics: Female; Humans; Ovariectomy; Salpingectomy; Salpingo-oophorectomy
PubMed: 32028509
DOI: 10.1097/AOG.0000000000003733 -
Archives of Oral Biology Sep 2019This study aimed to investigate the effect of risedronate on orthodontic tooth movement in ovariectomized rats.
OBJECTIVE
This study aimed to investigate the effect of risedronate on orthodontic tooth movement in ovariectomized rats.
METHODS
Forty-five female Sprague-Dawley rats were divided into three groups. Bilateral ovariectomies were performed on the rats in the ovariectomy and ovariectomy + risedronate groups. Two weeks after ovariectomy, risedronate was administered intraperitoneally every three days in the ovariectomy + risedronate group, while rats in the ovariectomy and sham groups were administered saline until they were sacrificed. One month after ovariectomy, nickel-titanium alloy closed-coil springs were placed between the maxillary left first molar and the maxillary left incisor. On days 3, 7 and 14, five rats from each group were sacrificed. The distance of orthodontic tooth movement was measured by a digital caliper, and slides were obtained for histological analysis.
RESULTS
The distance of orthodontic tooth movement and the number of tartar-resistant acid phosphatase (TRAP)-positive cells were the highest in the ovariectomy group, followed by those in the ovariectomy + risedronate group, on days 3, 7 and 14. The positive expression levels of receptor activator of nuclear factor-kappa β (RANK) ligand and cathepsin K were the strongest while the positive expression of osteoprotegerin in the ovariectomy group was the weakest, followed by the corresponding expression levels in the ovariectomy + risedronate group, on days 3, 7 and 14.
CONCLUSIONS
Risedronate can inhibit orthodontic tooth movement in ovariectomized rats and may function by regulating the RANK/RANK ligand/osteoprotegerin pathway.
Topics: Animals; Cathepsin K; Female; Osteoclasts; Osteoprotegerin; Ovariectomy; RANK Ligand; Rats; Rats, Sprague-Dawley; Risedronic Acid; Tooth Movement Techniques
PubMed: 31276939
DOI: 10.1016/j.archoralbio.2019.06.007 -
Stroke Oct 2022Little is known about the long-term risks of stroke and ischemic heart disease (IHD) in women who had a hysterectomy alone (HA) or with bilateral oophorectomy (HBO) for...
BACKGROUND
Little is known about the long-term risks of stroke and ischemic heart disease (IHD) in women who had a hysterectomy alone (HA) or with bilateral oophorectomy (HBO) for benign diseases, particularly in China where the burden of cardiovascular diseases (CVD) is high. We assessed mean levels of cardiovascular risk factors and relative risks of stroke and IHD in Chinese women who had a HA or HBO.
METHODS
A total of 302 510 women, aged 30 to 79 years were enrolled in the China Kadoorie Biobank from 2004 to 2008 and followed up for a mean of 9.8 years. The analysis involved premenopausal women without prior cardiovascular disease or cancer at enrollment. We calculated adjusted hazard ratios for incident cases of CVD and their pathological types (ischemic stroke, hemorrhagic stroke, and IHD) after HA and HBO. Analyses were stratified by age and region and adjusted for levels of education, household income, smoking status, alcohol consumption, physical activity, body mass index, systolic blood pressure, diabetes, self-reported health, and number of pregnancies.
RESULTS
Among 282 722 eligible women, 8478 had HA, and 1360 had HBO. Women who had HA had 9% higher risk of CVD after HA (hazard ratio, 1.09 [95% CI, 1.06-1.12]) and 19% higher risk of CVD after HBO (1.19 [95% CI, 1.12-1.26]) compared with women who did not. Both HA and HBO were associated with higher risks of ischemic stroke and IHD but not with hemorrhagic stroke. The relative risks of CVD associated with HA and HBO were more extreme at younger age of surgery.
CONCLUSIONS
Women who had either HA or HBO have higher risks of ischemic stroke and IHD, and these risks should be evaluated when discussing these interventions. Additional screening for risk factors for CVD should be considered in women following HA and HBO operations, especially if such operations are performed at younger age.
Topics: Cardiovascular Diseases; China; Female; Hemorrhagic Stroke; Humans; Hysterectomy; Ischemic Stroke; Myocardial Ischemia; Ovariectomy; Risk Factors; Stroke
PubMed: 35862220
DOI: 10.1161/STROKEAHA.121.037305 -
Life Sciences Aug 2023Roflumilast, a well-known phosphodiesterase-4 (PDE-4) inhibitor, possess an anti-inflammatory activity with approved indications in chronic obstructive pulmonary...
AIMS
Roflumilast, a well-known phosphodiesterase-4 (PDE-4) inhibitor, possess an anti-inflammatory activity with approved indications in chronic obstructive pulmonary disease. This study aimed to evaluate the neuroprotective role of roflumilast in ovariectomy (OVX)-induced depressive-like behavior in female rats and to shed light on a potential autophagy enhancing effect.
MAIN METHODS
Rats were randomly divided into four groups: sham, OVX, OVX + roflumilast (1 mg/kg, p.o), and OVX + roflumilast + chloroquine (CQ) (50 mg/kg, i.p). Drugs were administered for 4 weeks starting 2 weeks after OVX.
KEY FINDINGS
Roflumilast improved the depressive-like behaviors observed in OVX rats as evidenced by decreasing both forced swimming and open field immobility times while, increasing % sucrose preference and number of open field crossed squares. Histopathological analysis provides further evidence of roflumilast's beneficial effects, demonstrating that roflumilast ameliorated the neuronal damage caused by OVX. Roflumilast antidepressant potential was mediated via restoring hippocampal cAMP and BDNF levels as well as down-regulating PDE4 expression. Moreover, roflumilast revealed anti-inflammatory and anti-apoptotic effects via hindering TNF-α level and diminishing Bax/Bcl2 ratio. Roflumilast restored the autophagic function via up-regulation of p-AMPK, p-ULK1, Beclin-1 and LC3II/I expression, along with downregulation of P62 level and p-mTOR protein expression. The autophagy inhibitor CQ was used to demonstrate the suggested pathway.
SIGNIFICANCE
The present study revealed that roflumilast showed an anti-depressant activity in OVX female rats via turning on AMPK/mTOR/ULK1-dependent autophagy pathway; and neurotrophic, anti-inflammatory, and anti-apoptotic activities. Roflumilast could offer a more secure alternative to hormone replacement therapy for postmenopausal depression treatment.
Topics: Animals; Female; Rats; AMP-Activated Protein Kinases; Autophagy; Autophagy-Related Protein-1 Homolog; Intracellular Signaling Peptides and Proteins; Ovariectomy; Phosphodiesterase 4 Inhibitors; TOR Serine-Threonine Kinases; Depression
PubMed: 37257579
DOI: 10.1016/j.lfs.2023.121806 -
BioMed Research International 2021To establish a novel animal model of intervertebral disc degeneration (IVDD) in rats and to investigate the effect of 17-estradiol (E2) intervention in this model.
OBJECTIVES
To establish a novel animal model of intervertebral disc degeneration (IVDD) in rats and to investigate the effect of 17-estradiol (E2) intervention in this model.
METHODS
This study was divided into two parts: animal model (four groups: Sham, ovariectomy (OVX), Puncture, and OVX+Puncture; three-time points: 4, 8, and 12 weeks; three female rats/group/time point) and drug intervention (Sham, OVX+Puncture+corn oil, and OVX+Puncture+E2; three female rats/group). The rats were analyzed by micromagnetic resonance imaging (MRI), hematoxylin and eosin (HE) staining, and safranin-O staining.
RESULTS
MRI and histological scores significantly differed among the four groups at the three-time points (all < 0.05). IVDD progressed with time in the OVX, Puncture, and OVX+Puncture groups (all < 0.05). The changes were the most obvious in the OVX+Puncture group. In the E2 intervention part, the Veh group had the worst MRI signals and histological scores ( < 0.05). The MRI scores in the E2 group were less obvious compared to the Sham group ( > 0.05). Also, the histological scores were significantly different between the Sham and E2 groups ( < 0.05).
CONCLUSIONS
The combination of ovariectomy and needle puncture can synergically induce IVDD in rat coccygeal discs. Estrogen treatment can effectively ameliorate IVDD progression in the newly established IVDD models.
Topics: Animals; Disease Models, Animal; Estradiol; Estrogens; Female; Intervertebral Disc; Intervertebral Disc Degeneration; Magnetic Resonance Imaging; Needles; Ovariectomy; Punctures; Rats; Rats, Sprague-Dawley
PubMed: 34055972
DOI: 10.1155/2021/5510124 -
Nutrients Aug 2022The fruit of Hippophae rhamnoides has been widely used for medicinal purposes because of its anti-inflammatory, antioxidant, antiplatelet, and antimicrobial effects....
The fruit of Hippophae rhamnoides has been widely used for medicinal purposes because of its anti-inflammatory, antioxidant, antiplatelet, and antimicrobial effects. Since there are no clear reports on the therapeutic efficacy of H. rhamnoides in osteoporosis, this study aimed to confirm the potential use of H. rhamnoides for the treatment of osteoporosis through its osteogenic differentiation-promoting effect in ovariectomized mice. Through an in vitro study, we compared the effects of the EtOH extract of H. rhamnoides fruits (EHRF) on the differentiation of C3H10T1/2, a mouse mesenchymal stem cell line, into osteoblasts based on alkaline phosphatase (ALP) staining and the relative expression of osteogenesis-related mRNAs. The EHRF significantly stimulated the differentiation of mesenchymal stem cells into osteoblasts and showed 7.5 times (* p < 0.05) higher osteogenesis than in the untreated control. A solvent fractionation process of EHRF showed that the hexane-soluble fraction (HRH) showed 10.4 times (** p < 0.01) higher osteogenesis than in the untreated control. Among the subfractions derived from the active HRH by preparative HPLC fractionation, HRHF4 showed 7.5 times (* p < 0.05) higher osteogenesis than in the untreated naïve cells, and HRH and HRHF4 fractions showed 22.6 times (*** p < 0.001) stronger osteogenesis activity than in the negative control. Osteoporosis was induced by excision of both ovaries in 9-week-old female ICR mice for in vivo analysis, and two active fractions, HRH and HRHF4, were administered orally for three months. During the oral administration period, body weight was measured weekly, and bone mineral density (BMD) and body fat density were measured simultaneously using a DEXA machine once a month. In particular, during the in vivo study, the average BMD of the ovariectomized group decreased by 0.0009 g/cm2, whereas the average BMD of the HRH intake group increased by 0.0033 g/cm2 (* p < 0.05) and that of the HRHF4 intake group increased by 0.0059 g/cm2 (** p < 0.01). The HRH and HRHF4 intake groups significantly recovered the mRNA and protein expression of osteogenic genes, including ALP, Osteopontin, Runx2, and Osterix, in the osteoporosis mouse tibia. These findings suggest that the active fractions of H. rhamnoides fruit significantly promoted osteoblast differentiation in mesenchymal stem cells and increased osteogenic gene expression, resulting in an improvement in bone mineral density in the osteoporosis mouse model. Taken together, H. rhamnoides fruits are promising candidates for the prevention and treatment of osteoporosis.
Topics: Animals; Cell Differentiation; Female; Fruit; Hippophae; Humans; Mice; Mice, Inbred ICR; Osteogenesis; Osteoporosis; Ovariectomy
PubMed: 36079860
DOI: 10.3390/nu14173604 -
Indian Journal of Pharmacology 2021Studies have shown that there is a critical time period to start hormone therapy after the loss of ovarian function during menopause. The length of estrogen deprivation...
BACKGROUND
Studies have shown that there is a critical time period to start hormone therapy after the loss of ovarian function during menopause. The length of estrogen deprivation may evolve different pathophysiological manifestations.
OBJECTIVE
The aim of the present study was to investigate behavioral, biochemical, and molecular alterations at different time points after surgical menopause with an aim and identify various pathophysiological targets to exploit "window of opportunity" and to design newer therapeutic modalities for menopause-associated neurobehavioral and vascular deficits.
MATERIALS AND METHODS
Bilateral ovariectomy was performed to induce surgical menopause and estrogen deficiency state. Menopause-associated neuronal and vascular dysfunctions were noted after 1, 2, and 3 months of the study.
RESULTS
Neuronal and vascular endothelial dysfunction post ovariectomy revealed that behavioral, biochemical, molecular, and vascular endothelial dysfunction appeared after 1 month of ovariectomy except hyperglycemia, which occurs after 3 months.
CONCLUSIONS
Time-response studies measuring behavioral, biochemical, and molecular markers at various time points after ovariectomy reveal that there is a fast onset of neuronal and vascular complications, but the duration of insulin resistance is a relatively late phenomenon.
Topics: Animals; Disease Models, Animal; Endothelium, Vascular; Female; Menopause; Neurons; Ovariectomy; Rats; Rats, Sprague-Dawley
PubMed: 33975997
DOI: 10.4103/ijp.IJP_233_18 -
Clinical Oral Implants Research Jul 2020The objective of the study was to evaluate and compare the effect of different drugs such as simvastatin, alendronate, and tibolone for titanium implant osseointegration...
OBJECTIVES
The objective of the study was to evaluate and compare the effect of different drugs such as simvastatin, alendronate, and tibolone for titanium implant osseointegration enhancement.
MATERIALS AND METHODS
Eighty female albino Wistar rats were equally divided into five groups: Group I (ovariectomy), Group II (sham ovariectomy), Group III (alendronate + ovariectomy), Group IV (simvastatin + ovariectomy), and Group V (tibolone + ovariectomy). Three months after ovariectomy, we performed bilateral titanium intramedullary nailing in all groups, followed by oral administration of alendronate, simvastatin, or tibolone for 12 weeks. Examinations included micro-CT, mechanical pull-out test, histology, and bone serum markers.
RESULTS
Peri-implant micro-CT analysis showed a significantly higher overall bone tissue in tibolone compared to the ovariectomy group, while no significant difference was found between the treatment groups. Sham ovariectomy, alendronate, and tibolone groups had a higher body mass density compared to ovariectomy and simvastatin groups. All treatment groups had a greater thickness of the peri-implant compact bone layer compared to ovariectomy group, but the results were not statistically significant. Tibolone presented the highest values in pull-out test, but alendronate showed more consistently positive results compared to other groups. Osteocalcin had in the tibolone group almost three times the value in the ovariectomy group, but the results were not statistically significant.
CONCLUSION
The hypothesis that alendronate, simvastatin, and tibolone enhance the osseointegration process of intramedullary titanium implants in ovariectomized rats has been accepted, while tibolone could offer the best results.
Topics: Alendronate; Animals; Bone Density; Dental Implants; Female; Humans; Norpregnenes; Osseointegration; Ovariectomy; Rats; Simvastatin; Titanium
PubMed: 32279374
DOI: 10.1111/clr.13602