Aspirin modified strontium-doped β-tricalcium phosphate can accelerate the healing of femoral metaphyseal defects in ovariectomized rats

European Journal of Pharmacology

Zhou

et al. 2021

Self Cite

Objective: the present work was aimed to evaluate the effect of different administration modes of sodium valproate(VPA) on bone strength, bone mass and bone mineral density in ovariectomized(OVX) rats and further investigation of the possible mechanism.Methods: 60 female SD rats were randomly divided into 4 groups: Sham group (Sham, n=15), OVX group (OVX, n=15), OVX rats received intermittent VPA treatment group(IVPA, n=15) and OVX rats received daily VPA treatment group(EVPA, n=15). After 12 weeks of treatment, the rats were sacri ced, and serum and femur samples were harvested. DEXA, Micro-CT, histology, biomechanical testing, biochemical index and western blot analysis were used to observe the therapeutic effect and explore the possible mechanism.Results: Micro-CT and DEXA analysis of bones revealed better BMD and higher BV/TV, Tb.Th, Tb.N, Conn. D and lower Tb.Sp at femoral metaphysis with evaluated in IVPA when compared with OVX and EVPA group(P 0.05). Histological, uorescent analysis and biological strength revealed more trabecular bone and higher relative mineral apposition rate, maximal load, elastic modulus and energy at break with evaluated in IVPA when compared with OVX and EVPA group(P 0.05). The levels of P1NP, estrogen, CTX, TRAP5b and RANKL of IVPA group showed a signi cant increase when compared with the OVX and EVPA group(P 0.05). We con rm adverse effects on protein expressions including Notch1, Jagged1, HEY1, Wnt 1, β-catenin and RUNX2 following daily VPA treatment in OVX female rats.Conclusions: Our current study demonstrated that intermittent administration sodium valproate has a protective effect on bone health in ovariectomized rats and these effects may be achieved by activating Notch/Wnt/β-catenin/ RUNX2 signal axis.

Section: Discussionsupporting

confidence: 86%

Intermittent administration sodium valproate has a protective effect on bone health in ovariectomized rats

European Journal of Pharmacology

Zhou

et al. 2021

Self Cite

“…HE staining was performed using an HE staining kit (Solarbio, Beijing, China) according to the manufacturer's instructions. After staining the bone tissue, the images were collected with the ECLIPSE Ti-U (Nikon), as previously described (Li et al 2021b ; Tao et al 2020 ).…”

Section: Methodsmentioning

confidence: 99%

Probucol promotes osteoblasts differentiation and prevents osteoporosis development through reducing oxidative stress

Wei

2022

Mol Med

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Probucol (PBC) is a potent cholesterol-lowering drug and has been studied extensively for its powerful antioxidative stress. The purpose of this study is to investigate the role of PBC in ovariectomized rat model and to explore the mechanism of osteogenic differentiation of MC3TE-E1 Cells. RT-qPCR and Immunofluorescence were used to measure the expression level of SOD2, SIRT1, intracellular oxidative stress levels and osteogenic markers proteins. Moreover, CCK-8 assay was conducted to detect cell viability. Alizarin red staining and alkaline phosphatase staining were applied to examine osteogenic function and calcium deposits. The ovariectomized rat model was set up successfully and HE staining were employed to examine femoral trabeculae tissue. Our results showed that PBC suppressed MC3TE-E1 resist oxidative stress to promote osteogenic differentiation. Additionally, it was confirmed that PBC promoted osteogenic differentiation of MC3TE-E1 through inhibiting oxidative stress. Further study indicated that PBC exerted its beneficial function by suppressing oxidative stress-mediated alter bone metabolism to alleviate osteoporosis in vivo. Our research suggested that the PBC-modulated oxidative stress inhibition is responsible for activation of the process of osteogenic differentiation, providing a novel insight into the treatment of osteoporosis. Graphical abstract

“…12 weeks after sham operation(Sham) and bilateral ovariectomy(OVX), all rats were randomly divided into 3 groups: Sham group (Sham), OVX rats group (OVX) and OVX rats + silybin treatment group (SIL+OVX). Next, the rats of three groups established an intramedullary defect in the distal femur (1.5 mm in diameter×4mm in depth) using a 1.5 mm diameter clinical drill bits(Stryker Corporation, US) as described previously [22,23]. The rats were classi ed to SIL+OVX were treated with silibinin intraperitoneally with a dose of 50mg/kg (Sigma-Aldrich) [24].…”

Section: Animal Experimentsmentioning

confidence: 99%

Silibinin Promotes Bone Regeneration Through HIF-1α/VEGF and Notch Signaling Pathway in Ovariectomized Rats

Yang

et al. 2021

Preprint

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Objective The purpose was to observe whether systemic administration with silibinin(SIL) have an positive effect on bone defect regeneration through HIF-1α/VEGF and Notch signaling pathway in an ovariectomized(OVX) rat model. Methods The MC3T3-E1 cells were co-cultured with lower SIL and higher SIL and induced to osteogenesis, and the cell viability, osteogenic activity were observed by Cell Count Kit-8(CCK-8), Alkaline phosphatase (ALP) staining, Alizarin Red(RES) staining and Western blotting(WB). After the drilling defect model was established, the OVX rats were treated with SIL for 12 weeks. Micro-CT, histology and Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis were used to observe the therapeutic effect and explore the possible mechanism. Results CCK-8, ALP and ARS staining results show that the cell mineralization and osteogenic activity of LSIL and HSIL group is significantly higher than the Con group. Protein expressions show that related regulatory proteins such as ALP, OPN, RUNX-2, OC, VEGFA, HIF-1α, Notch 1, JAG 1, HEY 1 and HES 1 of LSIL and HSIL group are significantly higher than Con group. Micro-CT and Histological analysis evaluation show that group SIL + OVX presented the stronger effect on bone regeneration, bone mineralization, higher expression of VEGFA and HIF-1α, when compared with OVX group. RT-qPCR analysis shows that SIL + OVX group showed increased Notch 1, HES1, HEY1 and JAG1 than the OVX group(p < 0.05). Conclusions Our current study demonstrated that systemic administration with SIL is a scheme for rapid repair of femoral condylar defects, and these effects may be achieved by activating HIF-1α/VEGF and Notch signaling pathway.