Berberine coated mannosylated liposomes curtail RANKL stimulated osteoclastogenesis through the modulation of GSK3 β pathway via upregulating miR-23a.

Berberine coated mannosylated liposomes curtail RANKL stimulated osteoclastogenesis through the modulation of GSK3β pathway via upregulating miR-23a. Int Immunopharmacol. 2019 Jun 28;74:105703 Authors: Sujitha S, Rasool M Abstract Drug-induced microRNAs manifest significant therapeutic approaches; however, such progress in the treatment of osteopathic disorders including osteoporosis and rheumatoid arthritis still remains obscure. Contrarily, non-specific drug delivery, at high doses, increases the risk of side effects and reduces drug therapeutic efficacy. Accordingly, the present study was designed to examine the therapeutic effect of berberine coated mannosylated liposomes (ML-BBR) on RANKL (100 ng/ml) stimulated bone marrow-derived monocytes/macrophages (BMMs) via altering miR-23a expression. Initial studies using confocal microscopy showed successful internalization of ML-BBR in RANKL stimulated BMMs. Treatment with ML-BBR abrogated the increased osteoclast formation in BMM cells via inhibiting phosphorylated glutathione synthase kinase beta (p-GSK3β) mediated NFATc1 activation. Consequently, ML-BBR also attenuated the expression of bone-degrading enzymes (TRAP, cathepsin K and MMP-9) thereby inhibiting the bone resorptive activity of osteoclasts. Moreover, ML-BBR induced the expression levels of miR-23a at the gene level, which in turn attenuated GSK3β/p-GSK3β expression as confirmed via blotting analysis. Further miR-23a...
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research