Combination of magnesium ions and vitamin C alleviates synovitis and osteophyte formation in osteoarthritis of mice

Introduction:We previously demonstrated that magnesium ions(Mg^(2+))was a novel therapeutic alternative for osteoarthritis(OA)through promoting the hypoxia inducible factor-1α(HIF-1α)-mediated cartilage matrix synthesis.However,oxidative stress can inhibit the expression of HIF-1α,amplify the inflammation that potentially impairs the therapeutic efficacy of Mg^(2+) in OA.Vitamin(VC),a potent antioxidant,may enhance the efficacy of Mg^(2+) in OA treatment.This study aims to investigate the efficacy of combination of Mg^(2+)and VC on alleviating joint destruction and pain in OA.Material and methods:Anterior cruciate ligament transection with partial medial meniscectomy induced mice OA model were randomly received intra-articular injection of either saline,MgCl2(0.5 mol/L),VC(3 mg/ml)or MgCl2(0.5 mol/L)plus VC(3 mg/ml)at week 2 post-operation,twice weekly,for 2 weeks.Joint pain and pathological changes were assessed by gait analysis,histology,western blotting and micro-CT.Results:Mg^(2+) and VC showed additive effects to significantly alleviate the joint destruction and pain.The efficacy of this combined therapy could sustain for 3 months after the last injection.We demonstrated that VC enhanced the promotive effect of Mg^(2+) on HIF-1αexpression in cartilage.Additionally,combination of Mg^(2+) and VC markedly promoted the M2 polarization of macrophages in synovium.Furthermore,combination of Mg^(2+) and VC inhibited osteophyte formation and expressions of pain-related neuropeptides.Conclusions:Intra-articular administration of Mg^(2+)and VC additively alleviates joint destruction and pain in OA.Our current formulation may be a cost-effective alternative treatment for OA.

An alternative splicing variant of mineralocorticoid receptor discovered in preeclampsia tissues and its effect on endothelial dysfunction

The pathophysiology of preeclampsia(PE)remains unclear.PE spiral artery remodeling dysfunction and PE offspring cardiovascular future development has been a worldwide concern.We collected placental and umbilical artery samples from normotensive and PE pregnancies.Mineralocorticoid receptor(MR)and its alternative splicing variant(ASV)expression and their biological effects on PE were examined.An MR ASV was found to be highly expressed in all PE samples and slightly expressed in about half of the normotensive samples(umbilical artery,~57.58%;placenta,~36.84%).The MR ASV expression was positively associated with blood pressure in both groups.The MR ASV protein changed the aldosterone-induced expression pattern of MR target genes related to ion exchanges and cell signaling pathways.The MR ASV can also impair the proliferation,migration,and tube formation ability of endothelial cells.These findings indicate that MR ASV in PE placenta plays a pathogenic role in PE pathophysiology,especially in endothelial dysfunction,and the existence of the MR ASV in PE umbilical artery provides a new direction in the study of PE offspring with increased risk of cardiovascular diseases.