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

Abstract

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.

Hydrogel contained valproic acid accelerates bone-defect repair via activating Notch signaling pathway in ovariectomized rats

“…In vitro experimental studies have reported that VPA regulates cell histone acetylation to accelerate osteoblast differentiation and the maturation processes [ 13 , 14 ]. Interestingly, several cellular and our previous animal experiment have shown VPA’s beneficial effects on bone health [ 15 – 18 ].…”

Favorable osteogenic activity of vericiguat doped in β-tricalcium phosphate: In vitro and in vivo studies

“…18 This could be particularly beneficial for patients with osteoporosis or those at risk of fractures, as it could potentially improve their bone health and reduce the risk of fractures. 30 On the other hand, VIT may have a negative effect on osteoclast activity, which is essential for bone resorption. 21 By inhibiting osteoclast function, VIT could potentially lead to an imbalance in bone metabolism, with a decrease in bone resorption rates.…”

Co-modified 3D printed β-tricalcium phosphate with magnesium and selenium promotes bone defect regeneration in ovariectomized rat

“…These femurs were incubated in 10% EDTA (pH 7.4) at 4 °C for 4 weeks before paraffin-embedding. The longitudinally oriented bone defect sections with 4-µm-thick were collected for HE staining and immunohistochemical staining as previously described [ 19 , 32 ]. In brief, histological examination of decalcified sections were performed by staining with HE for light microscopy.…”