Kefir peptides ameliorate osteoporosis in AKR1A1 knockout mice with vitamin C deficiency by promoting osteoblastogenesis and inhibiting osteoclastogenesis

作者：Gary Ro‐Lin Chang, Wei‐Yu Lin, Hueng‐Chuen Fan, Min‐Yu Tu, Yu-Hsien Liu, Chih‐Ching Yen, Abdulkadir Cidem, Wei Chen, Chuan‐Mu Chen · 发表于：Biomedicine & Pharmacotherapy · 年份：2022 · DOI：10.1016/j.biopha.2022.113859 · 被引用次数：19 · 研究领域：Aldose Reductase and Taurine、Vitamin C and Antioxidants Research、Fluoride Effects and Removal

The AKR1A1 protein is a member of the aldo-keto reductase superfamily that catalyzes the transformation of D -glucuronate to L -gulonate in the synthesis of L -ascorbic acid (vitamin C, Vit C). We previously demonstrated that AKR1A1 knockout mice ( AKR1A1 eGFP/eGFP ) with Vit C deficiency exhibited aberrant bone formation and osteoporosis. In this study, we aimed to evaluate the osteoprotective effects of kefir peptides (KPs) in AKR1A1 eGFP/eGFP mice and uncover the underlying mechanism of KPs in the modulation of bone remodeling. Six male CD-1 mice and 24 male AKR1A1 eGFP/eGFP mice were used in this study, in which the AKR1A1 eGFP/eGFP mice were randomly divided into four groups (n = 6). KPs treatment for 12 weeks exerted several effects in AKR1A1 eGFP/eGFP mice including the reduction of serum proinflammatory cytokines (IL-1β, IL-6, TNF-α), bone resorption markers (CTX-1, RANKL), and the increase of serum bone formation markers (P1NP, OPG, OC). μ-CT analysis indicated that KPs prevented the bone loss in the femurs of AKR1A1 eGFP/eGFP mice by significantly increasing the trabecular parameters of bone mineral density, bone volume and bone number. Nanoindentation analysis demonstrated that KPs enhanced the elasticity and hardness of femoral cortical bones in AKR1A1 eGFP/eGFP mice. KPs promoted bone marrow mesenchymal stem cells (BMMSCs)-derived osteoblast differentiation and mineralization by upregulating positive regulators of osteoblastogenesis (Runx2, β-catenin, BMP-2, NFAT...