Strontium-doped layered double hydroxides with nitrate as interlayer anion reverse osteoporotic microenvironment via triple actions of pro-osteogenic, anti-osteoclastic and anti-inflammatory in osteoporosis therapy

作者：Bangguo Wei, Hong Wang, Jintong Niu, Yi Gao, Chaoran Wu, Youyuan Li, Huichao Wang, Jiale Gao, Fang Wang, Yechang Qian, Guoxin Jing, Li Li, Shilong Wang · 发表于：Chemical Engineering Journal · 年份：2025 · DOI：10.1016/j.cej.2025.168567 · 被引用次数：5 · 研究领域：Bone Tissue Engineering Materials、Layered Double Hydroxides Synthesis and Applications、Graphene and Nanomaterials Applications

Osteoporosis is a prevalent skeletal disease and accompanied by bone resorption exceeds bone formation, and causes chronic inflammation. Osteoporotic microenvironment regulation is key to reversing osteoporosis progress. We synthesized pro-osteoblastic and anti-osteoclastic strontium (Sr) ion-doped MgAl-layered double hydroxides (Sr-LDHs) and Sr-undoped MgAl-layered double hydroxides (normal-LDHs) with Cl − or anti-inflammatory NO 3 − as interlayer anion. The addition of Sr and the interlayer anion of NO 3 − in LDHs enhanced the regulatory capacity of normal-LDHs through pro-osteogenic differentiation, anti-osteoclastic differentiation, and anti-inflammatory responses in vitro. RNA sequencing and gene expression assays revealed the regulatory mechanisms of Sr-LDHs in pro-osteogenesis (activating the Wnt/β-catenin pathway via the LGR5 receptor and activating the PI3K/AKT pathway via the PTGER3 receptor) and anti-osteoclastogenesis (suppressing NF-κB signaling and CaSR signaling). Compared with Cl − -intercalated LDHs, NO 3 − -intercalated LDHs activated the Wnt/β-catenin pathway via FZD3 receptor for pro-osteogenic differentiation, inhibited MAPK (ERK/JNK) signaling for anti-osteoclastic differentiation, and NF-κB signaling for anti-inflammation. In vivo, the addition of Sr and the interlayer anion of NO 3 − in LDHs synergistically enhanced the therapeutic efficacy of LDHs in preventing bone loss and restoring bone mass. This study demonstrated the functions and mechanisms of ...