This study investigated the protective effect of egg yolk hydrolysate (FC) on osteoporosis in ovariectomized (OVX) rats, a well-established model of postmenopausal bone loss. OVX rats were fed diets supplemented with 0.2% or 1% FC for 13 weeks. The regulatory effects were evaluated by measuring bone mineral density (BMD) and microarchitecture using computed tomography, analyzing serum bone remodeling biomarkers, and examining osteoclast differentiation and resorption activity in isolated bone marrow cells. Western blotting was used to evaluate the expression of key osteoclastogenic proteins. FC 1% supplementation significantly improved trabecular BMD and percentage bone volume in OVX rats. Treatment with FC 1% also significantly increased serum osteocalcin levels (P = 0.028). Furthermore, FC 1% significantly reduced osteoclast differentiation (decreased tartrate-resistant acid phosphatase-positive area by approximately 49%, P < 0.05) and bone resorption activity. At the molecular level, FC 1% significantly decreased cellular Fos (c-Fos) expression, whereas other osteoclastogenic proteins, including nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), cathepsin K and matrix metalloproteinase 9 (MMP-9), showed non-significant downward trends. These findings indicate that FC exerts moderate protective effects against bone loss in OVX rats by simultaneously suppressing osteoclast activity and enhancing bone formation. These results support the potential of egg yolk hydrolysate as a functional food ingredient for osteoporosis management, particularly in postmenopausal women. Further investigations are needed to fully understand the underlying mechanisms and assess long-term efficacy. © 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Apelin-13 induces lordosis behavior in estradiol-primed ovariectomized rats via the activation of multiple protein kinases in the ventromedial hypothalamus.

Isoliquiritigenin restores bone homeostasis in osteoporotic rats by enhancing BMSCs osteogenesis via ERK1/2-mTOR-HIF-1α-glycolytic axis and suppressing inflammation.

Inflammation is a central mediator linking metabolic dysfunction to severe human disease. Imbalance or loss of ovarian hormone (such as in post-menopausal women) contributes to increased risk of cardiovascular diseases, obesity and others. Here, using ovariectomized (OVX) Long-Evans rats as model for estrogen deprivation, we demonstrate that estrogen deprivation induces hepatic inflammation, activates tryptophan catabolism, systemic inflammation and disrupted cholesterol homeostasis. OVX animals gained more weight and developed an atherogenic plasma profile with increased LDL and total cholesterol and reduced HDL levels compared to intact female animals, which was reversed by estradiol (E2) administration. Ovariectomy results in elevation of hepatic pro-inflammation cytokine (e.g. TNFα, IL6), tryptophan catabolic enzymes (e.g. IDO1, and TDO2) and reduced reverse cholesterol associated gene SR-BI expression and E2- administration also suppressed the ovariectomy-induced hepatic inflammation resulting in reduction of TNFα, IL6, IDO1 and TDO2 while elevation of SR-BI expression. Plasma kynurenine, nitric oxide and lactate were elevated upon ovariectomy suggesting increased system Trp-catabolism, inflammation, each was reversed by estrogen. Targeted LC-MS metabolomics analysis revealed enhanced Trp-to-kynurenine flux, elevated lactate, accumulation of citrate/isocitrate/aconitate, and a reduced α-ketoglutarate/aconitate ratio (~ 0.6) restored by estradiol (~ 3.6). Together, our studies suggest a a link between estrogen signaling and hepatic immune-metabolism via regulation of Trp-catabolism, this open up potential novel signaling pathways for treating cardiometabolic disease and hormonal disorders.

Background Postmenopausal osteoporosis (PMOP) is characterized by high-turnover bone loss and oxidative stress. Astragaloside IV (AS-IV) exhibits antioxidant and immunomodulatory activities, yet its skeletal effects and mechanistic basis in ovariectomized (OVX) models remain incompletely defined. Methods Female Sprague–Dawley rats underwent bilateral ovariectomy. Six weeks after surgery, OVX rats were randomized to model, positive control, or AS-IV treatment (20/40/80 mg/kg, gavage, 8 weeks), with sham-operated controls. Serum bone-turnover markers (CTX-I, OCN, PTH) and oxidative stress markers (SOD, MDA) were measured by ELISA. Femora were assessed by micro-CT (BMD, BV/TV, Tb.N, Tb.Sp) and H&amp;amp;E staining. RNA sequencing was performed followed by GO/KEGG enrichment and WGCNA to identify hub genes, and molecular docking was used to evaluate AS-IV–target interactions. Multiplex immunofluorescence in the femoral trabecular bone quantified Lep, Ptgs2, Gfap, Igfbp2, Wnt1, β -catenin, and NF-κB p65 region (mean fluorescence intensity, normalized to Sham). Results OVX rats developed a clear high-turnover phenotype with trabecular rarefaction, reflected by higher CTX-I and MDA and lower SOD. AS-IV produced a dose-related improvement in these readouts—CTX-I fell, oxidative stress was eased (SOD increased and MDA decreased), and OCN and PTH moved back toward control levels. Histological analysis showed AS-IV treatment partially mitigated the trabecular deterioration observed in OVX rats. However, micro-CT analysis showed no statistically significant differences in trabecular bone structure between AS-IV-treated groups and OVX controls ( p &amp;gt; 0.05). RNA-seq identified osteoimmune and Wnt-centered programs and nominated hub genes including Lep, Ptgs2, Gfap, Igfbp2, Il22ra2, Wnt10a, and Wnt1. In femoral trabecular bone, multiplex immunofluorescence revealed increased NF-κB p65 and decreased Wnt1 and Gfap signals in OVX rats compared to Sham. High-dose AS-IV significantly reduced NF-κB p65 and partly restored Wnt1 and Gfap. However, Ptgs2 showed no significant differences across groups, and Igfbp2 and β -catenin were not significantly rescued within this sampling window. Molecular docking suggested favorable binding between AS-IV and selected targets, supporting its multitarget profile. Conclusion AS-IV modulates oxidative stress and osteoimmune–Wnt signaling in OVX rats, with directional improvements in bone turnover markers but without significant micro-CT structural changes. This work provides a foundation for hypothesis-driven investigation of AS-IV in PMOP.

Fecal microbiota transplantation ameliorates postmenopausal osteoporosis by restoring intestinal barrier function and suppressing inflammation in ovariectomized rats

Edible bird's nest attenuates menopausal syndromes by stimulating extragonadal estrogen biosynthesis in ovariectomized rats

This study investigated the role and underlying mechanism of large tumor suppressor 1/2 (LATS1/2), a core kinase in the Hippo pathway, in inhibiting osteoclastic differentiation and ameliorating ovariectomy (OVX)-induced osteoporosis in rats through the RANKL-dependent Hippo-YAP/TAZ signaling pathway both in vivo and in vitro. Under stimulation by receptor activator of nuclear factor-κB ligand (RANKL), small interfering RNA (siRNA) was used to suppress the expression of LATS1/2 and YAP. The levels of osteoclast-related genes and proteins, as well as YAP pathway proteins, were evaluated in RAW264.7 cells and bone marrow-derived macrophages (BMMs) via quantitative reverse transcription polymerase chain reaction and Western blot analysis. Cell viability and osteoclast formation potential were measured via the Cell Counting Kit-8 assay and tartrate-resistant acid phosphatase (TRAP) staining, respectively. Osteoclasts and filamentous actin were stained with TRAP and phalloidin to characterize cell morphology. Furthermore, to research the role of the Hippo/YAP pathway, we used siRNA to knock down LATS1/2 and examined its effect on RANKL-mediated osteoclast differentiation. In addition, we constructed an OVX-induced osteoporosis model in 8-week-old female Sprague‒Dawley rats, treated them with a LATS1/2 inhibitor for 4weeks at 12weeks after surgery, and evaluated the remission of osteoporosis by micro-CT and histological methods with a LATS1/2 inhibitor. After LATS1/2 was silenced or inhibited in BMMs and RAW264.7 cells, YAP was significantly upregulated and YAP phosphorylation and osteoclast function were inhibited. By interfering with YAP expression, the Hippo/YAP pathway inhibited osteoclast differentiation in BMMs. In vivo, injection of LATS1/2 inhibitor alleviated osteoporosis in ovariectomized rats. Our findings indicate that the inhibition of LATS1/2 considerably suppresses osteoclast differentiation and alleviates OVX-induced osteoporosis in rats. Additionally, our results show that LATS1/2 inhibitors are important for the differentiation of osteoclasts and highlight the possible therapeutic value of LATS1/2 inhibitors.

Selective estrogenic activity of Gouania longipetala Hemsl. (Rhamnaceae) aqueous extract through in vivo and in vitro antiproliferative approaches on MCF-7-167 and MDA-MB-231 cancer cells.

Early intermittent low-dose sclerostin antibody treatment promotes surface bone formation and reduces bone loss, but also decreases osteocyte apoptosis and mechanotransduction in ovariectomized rats: A pilot study.

Electroacupuncture remodels brain functional connectivity and improves bone metabolism in ovariectomized rats.

Stigmasterol upregulates Akt/mTOR/p70S6K signaling through SYVN1 to alleviate osteoporosis in ovariectomized rats.

Osteoporosis frequently presents with lower back pain, often accompanied by hypersensitivity, even in the absence of vertebral fractures, suggesting the involvement of central neuroinflammatory mechanisms. The activation of spinal glia has been implicated as a key driver of pain. Clinical and preclinical studies have also shown that teriparatide (TPTD), a bone anabolic drug, alleviates osteoporotic pain and raises the possibility of anti-neuroinflammatory effects. We previously reported that TPTD suppresses neuroinflammatory microglial proliferation in the spinal dorsal horn of an ovariectomized (OVX) rat model of postmenopausal osteoporosis. To further substantiate these previous findings, this study morphometrically investigated neuroinflammatory alterations in the same patho-pharmacological setting by establishing an AI-driven morphometric pipeline applied to DAB-stained bright-field images. OVX increased the number of microglia, induced process shortening and higher circularity, and expanded GFAP-positive astrocytic areas. TPTD partially attenuated OVX-induced glial changes. These findings indicate that OVX induces spinal neuroinflammation involving both microglia and astrocytes and that TPTD mitigates these neuroinflammatory responses. Moreover, the combination of 2D bright-field imaging and AI-driven morphometry represents a practical, accessible approach that requires minimal specialized equipment, yet sensitively captures OVX- and TPTD-induced microglial alterations, and enables phenotype-based classification.

Osteoporosis, a prevalent metabolic bone disorder characterized by diminished bone mass and microarchitectural deterioration, poses a significant global health burden. Bone marrow mesenchymal stem cells (BMMSCs) are crucial for bone homeostasis, and their declined osteogenic potential is a key pathogenic factor in osteoporosis. This study investigates the role of METTL14 in BMMSCs, hypothesizing that it attenuates osteoporosis progression by enhancing their osteogenic differentiation. Osteogenic and adipogenic differentiation were assessed by Alizarin Red and Oil Red O staining, respectively. Cell proliferation was evaluated using the CCK-8 assay, and protein expression was analyzed by Western blot. An ovariectomized (OVX) rat model of osteoporosis was established, with bone changes examined through histopathology and immunohistochemistry. Mitochondrial function was assessed via JC-1 staining, ROS/ATP assays, and respiratory chain protein expression analysis. METTL14 upregulation enhanced BMMSC proliferation, promoted osteogenic differentiation, and increased osteogenesis-related protein expression, whereas its suppression had opposing effects. In OVX rats, METTL14 elevation improved bone repair and improved mitochondrial function by recovering membrane potential, reducing mitochondrial ROS, increasing ATP production, and normalizing respiratory chain protein expression. METTL14 mitigates osteoporosis progression by promoting osteogenic differentiation of BMMSCs through improving mitochondrial dysfunction. Our research provides a foundation for targeting METTL14 in osteoporosis treatment.

Early menopause increases the risk for age-related macular degeneration (AMD), the most common cause of vision loss in industrialized countries. The supplementation with estradiol reduces the risk in these cases and suggesting that estradiol deficiency is a mediator of the risk association. We investigated rat models of estradiol deficiency mimicking either biological ageing (22 months of age) or early menopause by ovariectomy and age of 22 months. Serum analysis of gonadal hormones in both models showed the expected reduction in estradiol levels compared to 6 months old controls but also increases in progesterone, corticosterone and dehydroepiandrosterone sulfate (DHEA-S). Comparing the two estradiol deficiency models, we found no differences except for DHEA-S that were reduced in ovariectomized rats. The hormone status was associated with degenerative changes in the retina with higher activity of mononuclear phagocytes and p16/p21-dependent senescence. Mainly the estrogen receptor beta (ERβ) expressing cells were affected by estradiol deficiency: ganglion cells, cells of the inner nuclear layer (INL) and retinal pigment epithelial cells. An exception are photoreceptors that were ERβ negative, showed stronger degeneration in ovariectomized rats compared to sham treated animals. We conclude that either biological or ovariectomy induced estradiol deficiency might not cause but rather promote mechanisms that lead to AMD. The phenotype depends on a broader spectrum of altered hormones than on estradiol alone. Photoreceptor degeneration and cellular senescence that were ERβ independent in ovariectomized rats suggest non-estradiol effects to increase AMD risk by early menopause.

Endocrine-disrupting effects of titanium dioxide nanoparticles on the female reproductive system: Evidence from an ovariectomized rat model.

Osthole ameliorates cognitive impairment in ovariectomized rats via estrogen-mediated enhancement of cholinergic function and regulation of neurotransmitter homeostasis.

Circadian Rhythm-Aligned Time-Restricted Feeding Prevents Ovariectomy-Induced Fat Gain, Insulin Resistance, and Osteosarcopenia in Rats.

Piperazinotriazole-based NK3R antagonists: Rational design, synthesis, and identification of an orally active lead compound.

Calcium carbonate-enriched Cucurbita maxima increases the relative expression level of the PCSK9 gene in the liver of ovariectomized rats