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Protective effects of daphnetin against disuse osteoporosis in hindlimb unloading mic (A) Micro-CT images of trabecular bone in distal femur. (B) Trabecular BMD, BV/TV, BS/BV, trabe ular thickness (Tb. Th) and trabecular spacing (Tb. Sp) were calculated from the micro-CT data. (C Micro-CT images of cortical bone in mid-diaphysis femur. (D) Cortical BMD, BV/TV, BS/BV, Ct.T and Ct. Ar/Tt. Ar were calculated from the micro-CT data. To evaluate femoral mechanical prope ties, ultimate force (E), bending energy absorption (F), and elastic modulus (G) were determined b three-point bending test. (H) Hydroxyproline content of femur was determined with commerci kit. (I) Femur sections were prepared, and H & E staining was performed. Data are mean ±S.E.M. ≥ 6); * p < 0.05; ** p < 0.01.
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Senile and disuse osteoporosis have distinct bone turnover status and lack effective treatments. In this study, senescence-accelerated mouse prone 8 (SAMP8) and hindlimb unloading mouse models were used to explore the protective effects of daphnetin on these two types of osteoporosis, and primary osteoblasts and bone marrow monocyte-derived osteocl...
Contexts in source publication
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... and higher BS/BV, Tb. Sp, and daphnetin administration significantly reversed these changes (Figure 2A,B). Consistently, results in Figure 2C,D show that hindlimb unloading mice also exhibited lower BMD, BV/TV, Ct. ...
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... and daphnetin administration significantly reversed these changes (Figure 2A,B). Consistently, results in Figure 2C,D show that hindlimb unloading mice also exhibited lower BMD, BV/TV, Ct. Th, Ct. ...
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... and higher BS/BV of cortical bone, which were also effectively reversed by daphnetin administration. To investigate the effect of daphnetin on bone strength of hindlimb unloading mice, three-point bending test was successively performed, and the results show that daphnetin significantly enhanced ultimate force, bending energy absorption and elastic modulus under disuse conditions ( Figure 2E-G). The hydroxyproline content of bone tissue decreased significantly in hindlimb unloading mice, while daphnetin administration also effectively restored the collagen level ( Figure 2H). ...
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... investigate the effect of daphnetin on bone strength of hindlimb unloading mice, three-point bending test was successively performed, and the results show that daphnetin significantly enhanced ultimate force, bending energy absorption and elastic modulus under disuse conditions ( Figure 2E-G). The hydroxyproline content of bone tissue decreased significantly in hindlimb unloading mice, while daphnetin administration also effectively restored the collagen level ( Figure 2H). Histomorphometry analysis by H & E staining shows that the distal femoral bones of unloading group had lesser bone trabeculae and thinner cortical bones than that of the control group, while daphnetin-treated unloading group exhibited significantly increased bone volume and improved bone microstructure ( Figure 2I). ...
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... hydroxyproline content of bone tissue decreased significantly in hindlimb unloading mice, while daphnetin administration also effectively restored the collagen level ( Figure 2H). Histomorphometry analysis by H & E staining shows that the distal femoral bones of unloading group had lesser bone trabeculae and thinner cortical bones than that of the control group, while daphnetin-treated unloading group exhibited significantly increased bone volume and improved bone microstructure ( Figure 2I). Taken together, results in Sections 3.1 and 3.2 indicate that daphnetin can alleviate both senile osteoporosis and disuse osteoporosis. ...
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... and higher BS/BV, Tb. Sp, and daphnetin administration significantly reversed these changes ( Figure 2A,B). Consistently, results in Figure 2C,D show that hindlimb unloading mice also ex- , and cortical area to total area ratio (Ct. ...
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... and daphnetin administration significantly reversed these changes ( Figure 2A,B). Consistently, results in Figure 2C,D show that hindlimb unloading mice also ex- , and cortical area to total area ratio (Ct. Ar/Tt. ...
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... are mean ± S.E.M. (n ≥ 6); * p < 0.05; ** p < 0.01. hindlimb unloading mice, while daphnetin administration also effectively restored th collagen level ( Figure 2H ...
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... Materials: The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/antiox11122365/s1, Figure S1: Effects of daphnetin on cell viability of MC3T3-E1 and RAW264.7 cells at selected concentrations; Figure S2: Effects of daphnetin on SIRT3, mitochondrial homeostasis and antioxidant capacity of osteoblasts in SAMP8 mice; Figure S3: Effects of daphnetin on NOX cascade in osteoclasts of hindlimb unloading mice, as well as its effects on intracellular ROS content, SIRT3 and mitochondrial biogenesis of RAW264.7 cells; Table S1: Primer sequences used in real-time PCR of this study. ...
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... The senescence accelerated mouse (SAM) is a group of inbred mouse strains that have been developed through the backcrossing of AKR/J mice and subsequent phenotyping. This model is utilized for the study of human aging and agerelated diseases, such as cognitive disorders and osteoporosis [40,41]. It was determined that the expression levels of several genes involved in regulating skin function, such as Ela, Flg, Lor, Col1a1, Col1a2, and aquaporin-3, were reduced in 8-month-old SAMP1 mice compared to SAMR1 mice, which indicated SAMP mice could be a tool for analyzing skin aging [42]. ...
The skin, serving as the body’s primary defense against external elements, plays a crucial role in protecting the body from infections and injuries, as well as maintaining overall homeostasis. Skin aging, a common manifestation of the aging process, involves the gradual deterioration of its normal structure and repair mechanisms. Addressing the issue of skin aging is increasingly imperative. Multiple pieces of evidence indicate the potential anti-aging effects of exogenous nucleotides (NTs) through their ability to inhibit oxidative stress and inflammation. This study aims to investigate whether exogenous NTs can slow down skin aging and elucidate the underlying mechanisms. To achieve this objective, senescence-accelerated mouse prone-8 (SAMP8) mice were utilized and randomly allocated into Aging, NTs-low, NTs-middle, and NTs-high groups, while senescence-accelerated mouse resistant 1 (SAMR1) mice were employed as the control group. After 9 months of NT intervention, dorsal skin samples were collected to analyze the pathology and assess the presence and expression of substances related to the aging process. The findings indicated that a high-dose NT treatment led to a significant increase in the thickness of the epithelium and dermal layers, as well as Hyp content (p < 0.05). Additionally, it was observed that low-dose NT intervention resulted in improved aging, as evidenced by a significant decrease in p16 expression (p < 0.05). Importantly, the administration of high doses of NTs could improve, in some ways, mitochondrial function, which is known to reduce oxidative stress and promote ATP and NAD⁺ production significantly. These observed effects may be linked to NT-induced autophagy, as evidenced by the decreased expression of p62 and increased expression of LC3BI/II in the intervention groups. Furthermore, NTs were found to upregulate pAMPK and PGC-1α expression while inhibiting the phosphorylation of p38MAPK, JNK, and ERK, suggesting that autophagy may be regulated through the AMPK and MAPK pathways. Therefore, the potential induction of autophagy by NTs may offer benefits in addressing skin aging through the activation of the AMPK pathway and the inhibition of the MAPK pathway.
... In a recent study, mice were suspended from the hind limbs to establish a model of wasting OP, and subsequent administration of daphnetin maintained mitochondrial homeostasis by restoring the expression of SIRT3 and upregulating MnSOD to alleviate ROS in OCs, thus inhibiting OC differentiation and leading to decreased bone resorption. This suggests that daphnetin may inhibit bone resorption through the SIRT3/MnSOD pathway, thereby improving the progression of wasting OP, which may be useful for the clinical treatment of bedridden patients (Gao et al., 2022). ...
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